T Cells Redirected to EphA2 for the Immunotherapy of Glioblastoma

Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.     

Impact of pharmacy outreach services on blood pressure management in the elderly community of Hong Kong

Aim: To investigate the impact of the Pharmacy Outreach Service (POS) on blood pressure (BP) and disease knowledge among community‐dwelling elderly patients with hypertension, and to evaluate the sustainability of such impact of POS. Methods: A prospective open‐labeled study of elderly adults (aged ≥65 years) with hypertension (BP ≥140/90 mmHg for non‐diabetics and ≥130/80 mmHg for diabetics) was carried out at seven elderly community centers from July 2008 to March 2010. Pharmacists provided BP monitoring, medication review and disease knowledge assessment. The target BP was <140/90 mmHg for non‐diabetics and <130/80 mmHg for diabetics. The primary outcome was BP change, whereas the secondary outcome was the change of disease knowledge of hypertension. All outcomes were compared between baseline and the last visit. For POS 2008/09 participants, BP was compared between values obtained during POS 2008/09 and 2009/10. Results: A total of 97 participants were recruited. Systolic BP reduced significantly from 152.38 ± 18.80 mmHg to 147.04 ± 20.72 mmHg (P = 0.021), and diastolic BP reduced from 73.84 ± 11.36 mmHg to 71.03 ± 10.97 mmHg (P = 0.010). Cumulative reductions in mean systolic BP and diastolic BP throughout the 2‐year study period were 21.39 ± 24.72 mmHg and 9.88 ± 13.48 mmHg, respectively (P < 0.001). A 12% increase in the at‐goal rate was observed in new participants recruited in 2009 (P = 0.039). Disease knowledge of hypertension improved significantly (P < 0.005), particularly in areas that included the definition of hypertension, diet and lifestyle modification. Conclusions: The POS might improve blood pressure control, hypertension and diabetes knowledge in elderly adults with hypertension in Hong Kong. The effect on blood pressure improvement was sustainable. Geriatr Gerontol Int 2013; 13: 175–181.     

Suicidal Callers to a National Helpline in the UK: A Comparison of Depressive and Psychotic Sufferers

Little information is available on the profile of suicidal mentally ill sufferers seeking help from helplines. In this article we describe the profile and experience with services of suicidal people calling SANELINE, a national mental health helpline in the UK. Analyses were conducted on 1,331 calls made during 1996-1997 by callers who resided in London. Sixty-one percent of all callers were female. Half of all callers were suffering from depression and 32% from psychosis. Psychotic sufferers were significantly more likely not to have been complying with treatment, to have wanted information about medication, and to have been dissatisfied with the local services. Suicidal psychotic sufferers were more likely than non-suicidal ones to have inquired about mental health laws or about state benefits. On the other hand, depressive sufferers were more likely to have wanted information about social support groups, and to have complained about the lack of services in their area of residence. The findings suggested the need to target male sufferers, to meet the information needs of suicidal people with psychosis or depression, and to increase awareness about available sources of help.     

胫股关节吻合性对人工膝关节聚乙烯磨损的影响

人工关节置换术是矫正关节畸形、解除关节疼痛、重建关节功能的主要手段。多年来 ,人工全髋、全膝皆以聚乙烯为关节形成表面 ,随着人工关节置换的广泛开展 ,聚乙烯磨损问题越来越引起人们的关注。聚乙烯磨损及其产生的碎屑和磨损颗粒所引发的生物学反应及导致的骨吸收、骨溶解 ,是造成假体松动、人工关节翻修的主要原因[1,2 ] 。与人工髋关节的球洞几何形态相比 ,人工膝关节的几何形态要不吻合的多 ,胫骨假体表面常承受较大的接触应力 ,较易产生磨损[2 ,3 ] ,理论上关节形成表面越吻合 ,聚乙烯磨损越少 ,不同的胫股关节吻合性 ,对假体磨损产…     

State of the art and recommendationsKangaroo mother care: application in a high‐tech environment

Since Kangaroo Mother Care (KMC) was developed in Colombia in the 1970s, two trends in clinical application emerged. In low income settings, the original KMC model is implemented. This consists of continuous (24 h/day, 7 days/week) and prolonged mother/parent–infant skin‐to‐skin contact; early discharge with the infant in the kangaroo position; (ideally) exclusive breastfeeding; and, adequate follow‐up. In affluent settings, intermittent KMC with sessions of one or a few hours skin‐to‐skin contact for a limited period is common. As a result of the increasing evidence of the benefits of KMC for both infants and families in all intensive care settings, KMC in a high‐tech environment was chosen as the topic for the first European Conference on KMC, and the clinical implementation of the KMC model in all types of settings was discussed at the 7th International Workshop on KMC. Kangaroo Mother Care protocols in high‐tech Neonatal Intensive Care Units (NICU) should specify criteria for initiation, kangaroo position, transfer to/from KMC, transport in kangaroo position, kangaroo nutrition, parents’ role, modification of the NICU environment, performance of care in KMC, and KMC in case of infant instability. Conclusion: Implementation of the original KMC method, with continuous skin‐to‐skin contact whenever possible, is recommended for application in high‐tech environments, although scientific evaluation should continue.     

6种液煤馏分的分离及其元素分析

采用柱层析法将６种不同地区的液煤馏分进行了分离并对其中两种液煤馏分的分离产物进行了元素分析。     

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.