The Fictive Characteristics of Effective Educational Leaders

An article discussing the characteristics of effective leaders within education

Noninvasive electrocardiogram imaging of substrate and intramural ventricular tachycardia in infarcted hearts

AbstractObjectivesThe goal of this study was to experimentally evaluate a novel noninvasive electrocardiographic imaging modality during intramural reentrant ventricular tachycardia (VT).BackgroundMyocardial infarction and subsequent remodeling produce abnormal electrophysiologic substrates capable of initiating and maintaining reentrant arrhythmias. Existing noninvasive electrocardiographic methods cannot characterize abnormal electrophysiologic substrates in the heart or the details of associated arrhythmias. A noninvasive method with such capabilities is needed to identify patients at risk of arrhythmias and to guide and evaluate therapy.MethodsA dog heart with a four-day-old infarction was suspended in a human shaped torso-tank. Measured body surface potentials were used to noninvasively compute epicardial potentials, electrograms and isochrones. Accuracy of reconstruction was evaluated by direct comparison to measured data. Reconstructions were performed during right atrial pacing and nine cycles of VT.ResultsNoninvasively reconstructed potential maps, electrograms and isochrones identified: 1) the location of electrophysiologically abnormal infarct substrate; 2) the epicardial activation sequences during the VTs; 3) the locations of epicardial breakthrough sites; and 4) electrophysiologic evidence for activation of the Purkinje system and septum during the reentrant beats.ConclusionsElectrocardiographic imaging can noninvasively reconstruct electrophysiologic information on the epicardium during VT with intramural reentry, provide information about the location of the intramural components of reentry and image abnormal electrophysiologic substrates associated with infarction

Tumor Vasculature in Young and Old Hosts: Scanning Electron Microscopy of Microcorrosion Casts with Microangiography, Light Microscopy and Transmission Electron Microscopy

Tumor growth in vivo is dependent upon new blood vessel formation. When B16-F10 melanoma cells are implanted subcutaneously in young (3 mo) and old (24 mo) C57BL/6 mice the rate of growth is dependent on the age of the mice. This study involved a wide range of histological and microscopic techniques but was limited primarily to the initial phase of tumor growth. Stereological point counting from light microscopy (LM) of standard histological sections has been used to yield data regarding blood content. Tumor-bearing mice were perfused through the aorta with a fixation solution and were infused with a low-viscosity radiopaque gel (Microfil) or resin (Mercox). Soft x-rays of the whole animal were used for identifying the feeding vessels to the tumor. Tumors with Microfil were sliced and used for microangiography and light-microscopic observation while those with resin were used to make corrosion casts for scanning electron microscopy (SEM). The different characteristics of the tumor blood vessels in different aged mice were most obvious through SEM of vascular corrosion casts. In comparison with tumors in young mice those of similar size in old hosts had more necrosis, reduced presence of angiogenic features, decreased vessel density, reduced penetration into the tumor, and enhanced tortuosity of the vessel lumen. Transmission electron microscopy (TEM) revealed incompletely developed wall structure of the vessels regardless of host. The above results are consistent with the hypothesis that retarded angiogenesis may be responsible in part for the limited growth of tumors in old hosts

Age-associated modifications of intestinal permeability and innate immunity in human small intestine

The physical and immunological properties of the human intestinal epithelial barrier in aging are largely unknown. Ileal biopsies from young (7–12 years), adult (20–40 years) and aging (67–77 years) individuals not showing symptoms of gastrointestinal (GI) pathologies were used to assess levels of inflammatory cytokines, barrier integrity and cytokine production in response to microbial challenges. Increased expression of interleukin (IL)-6, but not interferon (IFN)γ, tumour necrosis factor (TNF)-α and IL-1β was observed during aging; further analysis showed that cluster of differentiation (CD)11c+ dendritic cells (DCs) are one of the major sources of IL-6 in the aging gut and expressed higher levels of CD40. Up-regulated production of IL-6 was accompanied by increased expression of claudin-2 leading to reduced transepithelial electric resistance (TEER); TEER could be restored in in vitro and ex vivo cultures by neutralizing anti-IL-6 antibody. In contrast, expression of zonula occludens-1 (ZO-1), occludin and junctional-adhesion molecule-A1 did not vary with age and overall permeability to macromolecules was not affected. Finally, cytokine production in response to different microbial stimuli was assessed in a polarized in vitro organ culture (IVOC). IL-8 production in response to flagellin declined progressively with age although the expression and distribution of toll-like receptor (TLR)-5 on intestinal epithelial cells (IECs) remained unchanged. Also, flagellin-induced production of IL-6 was less pronounced in aging individuals. In contrast, TNF-α production in response to probiotics (VSL#3) did not decline with age; however, in our experimental model probiotics did not down-regulate the production of IL-6 and expression of claudin-2. These data suggested that aging affects properties of the intestinal barrier likely to impact on age-associated disturbances, both locally and systemically

Mechanisms of Unexplained Anemia in the Nursing Home

To characterize anemia in elderly nursing home residents. Design : Prospective multiinstitutional cohort study. Setting : Five nursing homes. Participants : From retrospective analysis, residents found to be anemic using chart review were prospectively randomized. Of the 81 residents enrolled, 60 were anemic. Measurements : Chart review for medical history and factors related to treatment or history of anemia, extensive laboratory evaluation for causes of anemia, and classification of anemia by two hematologists. Results : Among the 60 anemic residents, the causes of anemia were idiopathic (n=27), iron-deficiency (n=14), anemia associated with chronic disease (n=8), anemia of renal insufficiency (n=6), and other (n=5). The eryrthropoietin (EPO) response to anemia was lower in residents with idiopathic anemia (IA) than in those with iron-deficiency anemia, and this correlated with renal function as estimated using calculated creatinine clearance. In this elderly population, advancing age was not correlated with lower EPO response. Conclusion : IA is common in nursing home residents. A lower EPO response contributes to the high prevalence of anemia in this setting and may be due, in part, to occult renal dysfunction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65745/1/j.1532-5415.2004.52116.x.pd

Immunogenetics of Aging’: report on the activities of the 15th International HLA and Immunogenetics Working Group and 15th International HLA and Immunogenetics Workshop

‘Immunogenetics of Aging’ is a component that was first included in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th Workshop. The aim of this component was to assess the impact of human leukocyte antigen (HLA) genes, cytokine genes, and some innate immunity genes such as killer-cell immunoglobulin-like receptors (KIRs) and mannose-binding lectin 2 (MBL2) in successful aging and their contribution to the better understanding of immune dysfunction in old age. Within the 15th IHIWS new populations were included in the analysis. Additional cytokine gene polymorphisms were assessed and innate immunity genes were analyzed for possible relevance in longevity. The results showed that longevity might be associated with anti-inflammatory cytokine gene profiles, decreased frequency of interleukin-10 (IL-10) and transforming growth factor-B1 haplotypes associated with a low level of gene expression, and increased frequency of haplotypes determining a high level of expression. Extended tumor necrosis factor-A and IL-12B genotypes were also likely relevant to longevity. Data also showed that innate immunity genes are associated with susceptibility to infections in the elderly and showed that these genes might be an important genetic marker in aging. Decreased frequencies of KIR2DS5 and A1B10 haplotypes, and an increased proportion of MBL2-deficient haplotypes were found in the group with higher cytomegalovirus-specific IgG antibody levels. Together, these studies emphasize the relevance of genes regulating immune functions in maintaining human longevity and stress the importance of further clarifying their impact on successful aging

Systemic inflammation in the genesis of frailty and sarcopenia: An overview of the preventative and therapeutic role of exercise and the potential for drug treatments

© 2017 by the author. The clinical, pathological and biological characteristics of frailty and sarcopenia are becoming better understood and defined, including the role of systemic inflammation. It is increasingly apparent that in older adults there is a tendency for the innate immune network to shift toward a pro-inflammatory setting, often due to the presence of chronic inflammatory diseases but also associated with age alone in some individuals. Furthermore, acute inflammation tends to resolve more slowly and less completely in many elderly people. Inflammation contributes to the pathogenesis of sarcopenia and other components of the frailty syndrome. Blood levels of inflammatory cytokines and acute phase proteins, are reduced by exercise, and there is a growing body of epidemiological, observational and intervention research that indicates that regular moderate exercise improves strength, function, morbidity and mortality in middle-aged and elderly adults. There is also an increasing awareness of the potential role of drugs to ameliorate inflammation in the context of frail old age, which might be particularly useful for people who are unable to take part in exercise programs, or as adjunctive treatment for those who can. Drugs that shift the innate immune biochemical network toward an anti-inflammatory setting, such as methyl-xanthines and 4-amino quinolones, could be of value. For example, theophylline has been shown to induce a 20 percent fall in pro-inflammatory tumor necrosis factor (TNF) and 180 percent rise in anti-inflammatory interleukin-10 production by peripheral blood monocytes, and a fall of 45 percent in interferon-gamma (IF-gamma) release. Such properties could be of therapeutic benefit, particularly to re-establish a less inflamed baseline after acute episodes such as sepsis and trauma

Sirt3, Mitochondrial ROS, Ageing, and Carcinogenesis

One fundamental observation in cancer etiology is that the rate of malignancies in any mammalian population increases exponentially as a function of age, suggesting a mechanistic link between the cellular processes governing longevity and carcinogenesis. In addition, it is well established that aberrations in mitochondrial metabolism, as measured by increased reactive oxygen species (ROS), are observed in both aging and cancer. In this regard, genes that impact upon longevity have recently been characterized in S. cerevisiae and C. elegans, and the human homologs include the Sirtuin family of protein deacetylases. Interestingly, three of the seven sirtuin proteins are localized into the mitochondria suggesting a connection between the mitochondrial sirtuins, the free radical theory of aging, and carcinogenesis. Based on these results it has been hypothesized that Sirt3 functions as a mitochondrial fidelity protein whose function governs both aging and carcinogenesis by modulating ROS metabolism. Sirt3 has also now been identified as a genomically expressed, mitochondrial localized tumor suppressor and this review will outline potential relationships between mitochondrial ROS/superoxide levels, aging, and cell phenotypes permissive for estrogen and progesterone receptor positive breast carcinogenesis

Oxidative Stress And Frailty: A Systematic Review And Best Evidence Synthesis

Objective: Oxidative stress (OS) is associated with accelerated aging. Previous studies have suggested a possible relationship between OS and frailty but this association remains unclear. We conducted a systematic review to investigate potential interactions between OS and frailty. Methods: A systematic literature search of original reports providing data on ‘OS and antioxidant’ parameters and frailty was carried out across major electronic databases from inception until May 2016. Cross-sectional/case control and longitudinal studies reporting data on the association between frailty and anti-oxidants-OS biomarkers were considered for inclusion. Results were summarized with a best-evidence based synthesis. Results: From 1,856 hits, 8 studies (cross-sectional/case control) were included (N = 6,349; mean age of 75 ± 12 years; 56.4% females). Overall, there were 588 (=9.3%) frail, 3,036 pre-frail (=47.8%), 40 (=0.6%) pre-frail/robust, and 2,685 (=42.3%) robust subjects. Six cross-sectional/case control studies demonstrated that frailty was associated with an increase in peripheral OS biomarkers including lipoprotein phospholipase A2 (studies = 1), isoprostanes (studies = 2), Malonaldehyde (studies = 2), 8-hydroxy-20-deoxyguanosine (studies = 2), derivate of reactive oxygen metabolites (studies = 2), oxidized Glutathione/Glutathione (studies = 1), 4-hydroxy-2,3-nonenal (studies = 1), and protein carbonylation levels (study = 1). In addition, preliminary evidence points to lower anti-oxidant parameters (vitamin C, E, α-tocopherol, biological anti-oxidant potential, total thiol levels) in frailty. Conclusion: Frailty and pre-frailty appear to be associated with higher OS and possibly lower anti-oxidant parameters. However, due to the cross sectional design, it is not possible to disentangle the directionality of the relationships observed. Thus, future high quality and in particular longitudinal research is required to confirm/refute these relationships and to further elucidate pathophysiological mechanisms