Age-related changes in the hippocampus (loss of synaptophysin and glial-synaptic interaction) are modified by systemic treatment with an NCAM-derived peptide, FGL

Altered synaptic morphology, progressive loss of synapses and glial (astrocyte and microglial) cell activation are considered as characteristic hallmarks of aging. Recent evidence suggests that there is a concomitant age-related decrease in expression of the presynaptic protein, synaptophysin, and the neuronal glycoprotein CD200, which, by interacting with its receptor, plays a role in maintaining microglia in a quiescent state. These age-related changes may be indicative of reduced neuroglial support of synapses. FG Loop (FGL) peptide synthesized from the second fibronectin type III module of neural cell adhesion molecule (NCAM), has previously been shown to attenuate age-related glial cell activation, and to 'restore' cognitive function in aged rats. The mechanisms by which FGL exerts these neuroprotective effects remain unclear, but could involve regulation of CD200, modifying glial-synaptic interactions (affecting neuroglial 'support' at synapses), or impacting directly on synaptic function. Light and electron microscopic (EM) analyses were undertaken to investigate whether systemic treatment with FGL (i) alters CD200, synaptophysin (presynaptic) and PSD-95 (postsynaptic) immunohistochemical expression levels, (ii) affects synaptic number, or (iii) exerts any effects on glial-synaptic interactions within young (4 month-old) and aged (22 month-old) rat hippocampus. Treatment with FGL attenuated the age-related loss of synaptophysin immunoreactivity (-ir) within CA3 and hilus (with no major effect on PSD-95-ir), and of CD200-ir specifically in the CA3 region. Ultrastructural morphometric analyses showed that FGL treatment (i) prevented age-related loss in astrocyte-synaptic contacts, (ii) reduced microglia-synaptic contacts in the CA3 stratum radiatum, but (iii) had no effect on the mean number of synapses in this region. These data suggest that FGL mediates its neuroprotective effects by regulating glial-synaptic interaction.     

Late breaking trials of 2015 in coronary artery disease: Commentary covering ACC,EuroPCR, SCAI,TCT, ESC,and AHA

The SCAI Publications Committee and Emerging Leadership Mentorship (ELM) Fellows concisely summarize and provide context on the most important coronary trials presented at large international meetings in 2015, including the MATRIX, ABSORB, and TOTAL trials. The intent is to allow quick assimilation of trial results into interventional practice, and enable busy interventional cardiologists to stay up to date. © 2016 Wiley Periodicals, Inc.     

Detecting Important Risk Factors of Survival Time of Lung Cancer Patients Using Censored Quintile Regression

Objective: Lung cancer is the most frequently diagnosed cancer and the most leading cause of death due to cancerworldwide. This study aimed to use censored quintile regression model to estimate the effect of potential risk factorson survival of lung cancer patients. Methods: In this study we used a dataset of a retrospective cohort study conductedin West Azerbaijan (during 2007 and 2014). Demographic variables included age, and gender and biological variablesincluded Eastern Cooperative Oncology Group, smoking, tumor type, stage, metastasis, and treatment were investigatedas risk factors of survival of lung cancer patients by using censored quintile regression. Result: The mean (± standarddeviation) age of the 347 lung cancer patients was 63.48 (± 13.55) years. The survival time ranges from 11 to 91. Atotal of 240 (67.6%) experienced death by the end of the study. The impact of Eastern Cooperative Oncology Group(IV), smoking and treatment were significant for most of quintiles (p<0.05). Stage of cancer and metastasis are the otheraffective risk factors on the survival of lung cancer patients(p<0.05). It was shown that Eastern Cooperative Oncology,smoking habit and treatment were significantly associated with a shorter time-to-death progression. Conclusion: Ascensored quintile regression could consider time-varying effects and the interpretation of its regression coefficients areeasy it could be an adequate choice for analyzing survival data.     

Intravascular T‐cell lymphoma: A rare,poorly characterized entity with cytotoxic phenotype

Intravascular T‐cell lymphomas are rare, poorly characterized lesions. We discuss the clinical, radiologic and especially the laboratory characteristics of a lesion which presented in a 62‐year‐old woman with a history of progressive CNS abnormalities. Throughout the course of the disease, radiologic findings consisted mainly of multifocal mixed areas of ischemia and vasogenic edema involving cortical and subcortical regions. A brain biopsy identified an abnormal T‐cell population confined to lumens of vessels. These T‐cells were abnormal cytotoxic cells, positive for CD3, CD8, and negative for CD2, CD4, CD5, CD7 and CD30. While flow cytometry and immunohistochemistry failed to identify a similar population in the blood or bone marrow, molecular studies showed a clonal T‐cell population in both the brain and the bone marrow. No other organs were involved. In spite of aggressive treatment, the patient's medical condition continued to progress and she passed away. In conclusion, this abnormal population of cytotoxic T‐cells with intravascular localization probably represents a specific type of T‐cell lymphoma with specific clinical, radiologic, molecular and immunophenotypic characteristics.     

A novel miniaturized multimodal bioreactor for continuous in situ assessment of bioartificial cardiac tissue during stimulation and maturation

Stem cell-based cardiac tissue engineering is a promising approach for regenerative therapy of the injured heart. At present, the small number of stem cell-derived cardiomyocytes that can be obtained using current culture and enrichment techniques represents one of the key limitations for the development of functional bioartificial cardiac tissue (BCT). We have addressed this problem by construction of a novel bioreactor with functional features of larger systems that enables the generation and in situ monitoring of miniaturized BCTs. BCTs were generated from rat cardiomyocytes to demonstrate advantages and usefulness of the bioreactor. Tissues showed spontaneous, synchronized contractions with cell orientation along the axis of strain. Cyclic stretch induced cardiomyocyte hypertrophy, demonstrated by a shift of myosin heavy chain expression from the alpha to beta isoform, together with elevated levels of atrial natriuretic factor. Stretch led to a moderate increase in systolic force (1.42?±?0.09?mN vs. 0.96?±?0.09?mN in controls), with significantly higher forces observed after β-adrenergic stimulation with noradrenalin (2.54?±?0.11?mN). Combined mechanical and β-adrenergic stimulation had no synergistic effect. This study demonstrates for the first time that mechanical stimulation and direct real-time contraction force measurement can be combined into a single multimodal bioreactor system, including electrical stimulation of excitable tissue, perfusion of the culture chamber, and the possibility of (fluorescence) microscopic assessment during continuous cultivation. Thus, this bioreactor represents a valuable tool for monitoring tissue development and, ultimately, the optimization of stem cell-based tissue replacement strategies in regenerative medicine.