Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.     

Comparison of Turkish Disability Policy,the United Nations Convention on the Rights of Persons with Disabilities,and the core concepts of U.S. disability policy

This article compares Turkey's Constitution and its Disabled Persons Act with the United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) and the core concepts of United States (U.S.) disability policy. Conclusions are that Turkey's Constitution and statutes are remarkably congruent with the UNCRPD and the core concepts. They are not, however, identical. This fact suggests that Turkey can still improve its statutes to reflect more closely the UNCRPD and core concepts. The review of these policy documents suggests that there are other steps Turkey can take to improve disability policy and its implementation. They are to amend Turkey's laws, determine the status of individuals and families affected by disability, and pursue vigorous implementation of their rights.     

Integration or specialization? Similarities and differences between Sweden and the United States in gerontology education and training

ABSTRACT

This article examines the similarities and differences in the education and training of gerontologists and others who work with older people in Sweden and the United States. It outlines the aging trends in both countries and assesses the level of training for those who provide care in a variety of fields. Both countries are aging, but the programs for gerontological training are quite different in the two countries, reflecting underlying cultural values. Sweden’s education is generally more oriented toward the integration of some aging education in more disciplinary fields, such as nursing and social work and thus could benefit from more specialized, aging-specific courses. The United States is highly specialized, with multiple programs in various subfields of aging (e.g., geropsychology; aging services administration) and could benefit from integrating more aging knowledge into courses in other disciplines. The authors challenge professionals to consider if there is a basic but global curriculum and/or set of competencies in gerontology that could be agreed upon. As an increasingly global village, the ability to share and learn is more easily achievable. Sweden and the United States have much to learn from each other in terms of appropriately educating and training those who support our older people.     

Testing for changing volatility

In this paper, we propose a consistent U‐statistic test with good sampling properties to detect changes in volatility. We show that the test has a limiting standard normal distribution under the null hypothesis, and that it is powerful compared with various alternatives. A Monte Carlo experiment is conducted to highlight the merits of the proposed test relative to other popular tests for structural changes in volatility. An empirical example is examined to demonstrate the practical application of the proposed testing method.     

MR‐detectable metabolic consequences of mitogen‐activated protein kinase kinase (MEK) inhibition

Metabolic reprogramming is increasingly being viewed as a hallmark of cancer. Accordingly, metabolic readouts can serve as biomarkers of response to therapy. The goal of this study was to investigate some of the MRS‐detectable metabolic consequences of mitogen‐activated protein kinase kinase (MEK) inhibition. We investigated PC3 prostate cancer, MCF‐7 breast cancer and A375 melanoma cells, and determined that, consistent with previous studies, MRS‐detectable levels of phosphocholine decreased significantly in all cell lines (to 63%, 50% and 18% of the control, respectively) following MEK inhibition with U0126. This effect was mediated by a decrease in the expression of choline kinase α, the enzyme that catalyzes the phosphorylation of choline. In contrast, the impact of MEK inhibition on glycolysis was cell line dependent. A375 cells, which express mutant BRAF, demonstrated significant decreases in glucose uptake (to 36% of control) and lactate production (to 42% of control) in line with positron emission tomography data. In contrast, in PC3 and MCF‐7 cells, increases in glucose uptake (to 198% and 192% of control, respectively) and lactate production (to 177% and 212% of control, respectively) were observed, in line with a previous hyperpolarized ¹³C MRS study. This effect is probably mediated by the activation of the phosphoinositide 3‐kinase pathway and AMP‐activated protein kinase. Our findings demonstrate the value of translatable non‐invasive MRS methods for the provision of information on cellular metabolism as an indication of the activation of potential feedback loops following MEK inhibition. Copyright © 2014 John Wiley & Sons, Ltd.     

Nitric Oxide: Biphasic Dose Responses

The capacity of nitric oxide (NO) to affect biphasic dose responses in pharmacological and toxicological systems was assessed. Numerous examples of such biphasic responses were documented, including osteoclast differentiation, various vascular responses, neutrophil migration, superoxide anion formation, exploratory behavior in rodents, vitamin D₃ levels in macrophages, human sperm motility and mobility, myocardial contraction, and other functions. The quantitative features of the dose response indicated a maximum stimulatory response usually less than twofold greater than the controls. While the stimulatory range was variable, ranging from ～2.5 to 500-fold, the majority was ≤10-fold. These findings indicate that biphasic dose-response relationships are common manifestations of the NO-induced effects.