The stress system effectively restores the internal balance--or homeostasis--of living organisms in the face of random external or internal changes, the stressors. This highly complex system helps organisms to provide a series of neuroendocrine responses to stressors--the stress response--through coordinated activation of the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus/norepinephrine autonomic nervous systems. In addition to stressors, life is influenced by daily light/dark changes due to the 24-h rotation of Earth. To adjust to these recurrent day/night cycles, the biological clock system employs the heterodimer of transcription factors circadian locomotor output cycle kaput/brain-muscle-arnt-like protein 1 (CLOCK/BMAL1), along with a set of other transcription factors, to regulate the circadian pattern of gene expression. Interestingly, the stress system, through the HPA axis, communicates with the clock system; therefore, any uncoupling or dysregulation could potentially cause several disorders, such as metabolic, autoimmune, and mood disorders. In this review, we discuss the biological function of the two systems, their interactions, and the clinical implications of their dysregulation or uncoupling.
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Approximate methods based on the static pushover are introduced to estimate the seismic performance uncertainty of structures having non‐deterministic modeling parameters. At their basis lies the use of static pushover analysis to approximate Incremental Dynamic Analysis (IDA) and estimate the demand and capacity epistemic uncertainty. As a testbed we use a nine‐storey steel frame having beam hinges with uncertain moment–rotation relationships. Their properties are fully described by six, randomly distributed, parameters. Using Monte Carlo simulation with Latin hypercube sampling, a characteristic ensemble of structures is created. The Static Pushover to IDA (SPO2IDA) software is used to approximate the IDA capacity curve from the appropriately post‐processed results of the static pushover. The approximate IDAs allow the evaluation of the seismic demand and capacity for the full range of limit‐states, even close to global dynamic instability. Moment‐estimating techniques such as Rosenblueth's point estimating method and the first‐order, second‐moment (FOSM) method are adopted as simple alternatives to obtain performance statistics with only a few simulations. The pushover is shown to be a tool that combined with SPO2IDA and moment‐estimating techniques can supply the uncertainty in the seismic performance of first‐mode‐dominated buildings for the full range of limit‐states, thus replacing semi‐empirical or code‐tabulated values (e.g. FEMA‐350), often adopted in performance‐based earthquake engineering. Copyright © 2009 John Wiley & Sons, Ltd.
A plethora of studies show that exposure of living organisms to man-made polarized and coherent electromagnetic fields (EMFs), especially in the Extremely Low Frequency (ELF) and the microwave/Radio Frequency (RF) bands, may lead to oxidative stress (OS) and DNA damage. DNA damage is associated with mutations, cell senescence, cell death, infertility, and other pathologies, including cancer. ELF EMF exposures from high-voltage power lines and complex "RF" EMF exposures from wireless communication (WC) antennas/devices have been associated with increased cancer risk. Almost all man-made microwave/RF EMFs, and especially those employed in WC, are combined with ELF components in the form of modulation, pulsation, and random variability. Thus, in addition to polarization/coherence, the existence of ELFs is a common feature of almost all man-made EMFs. Polarized/coherent ELF EMFs are predicted to induce dysfunction of voltage-gated ion channels (VGICs) in cell membranes through the ion forced oscillation mechanism, and this has been verified by many experimental studies. Dysfunction of VGICs disrupts intracellular concentrations of critical ions, such as calcium, sodium, potassium, etc. This condition initiates biochemical processes leading to OS by reactive oxygen species (ROS) overproduction. Such processes include a) increased calcium signaling, leading to nitric oxide (NO•) overproduction by the nitric oxide synthases (NOS) in various locations in the cell, and superoxide anion (O2•−) overproduction in the mitochondria; b) activation of NADPH/NADH oxidase in the plasma membrane, leading to increased production of O2•−; and c) dysfunction of the Na+/K+ pump (ATPase) in the plasma and internal cell membranes, triggering mitochondrial ROS production. At least these processes may result in excessive OS, leading to DNA damage and related diseases, including infertility and cancer. Thus, it seems that there is a plausible explanation for the genetic damage and related effects found to be induced by man-made EMF exposures as reported by many experimental and epidemiological studies.
▪ Abstract The diagnosis of endogenous Cushing's syndrome requires demonstration of an increased cortisol secretion rate, best achieved by urinary free cortisol excretion determinations. In borderline or confusing cases, loss of diurnal cortisol rhythmicity, a combined dexamethasone/corticotropin releasing hormone (CRH) test, or close monitoring of the patient for a few months will be helpful in ruling out pseudo- Cushing's. Primary adrenal Cushing's syndrome can be ruled out on the basis of a normal or elevated basal and/or CRH-stimulated plasma adrenocorticotropin (ACTH) and a negative adrenal computed tomography. ACTH-dependent Cushing's syndrome can then be differentiated on the basis of a CRH test and imaging procedures. A discrete pituitary lesion on magnetic resonance imaging and a standard CRH test with results consistent with such a lesion are sufficient to proceed to transsphenoidal surgery. If no discrete pituitary lesion is present, or if the CRH test is equivocal, bilateral simultaneous inferior petrosal sinus sampling with CRH administration is necessary to distinguish between a pituitary and an ectopic source. Surgery is the treatment of choice for all types of Cushing's syndrome. In the few cases in which transsphenoidal surgery fails or the disease recurs, repeat transsphenoidal surgery, or radiation therapy in association with mitotane treatment, is a reasonable alternative. Bilateral adrenalectomy effectively cures hypercortisolism if resection of the ACTH-secreting tumor is unsuccessful and radiation/medical therapy fails.
The objective of this study is to investigate whether the additional damage to building components caused by vertical ground shaking and its impact on estimated monetary losses warrants the extra computational effort needed to include this feature for standard risk assessment applications. As a case study, we consider a 2D model of a modern nine‐story steel frame building located at a high seismic hazard site in California. The structural and nonstructural demands are assessed via nonlinear dynamic analysis carried out using hazard‐consistent bi‐directional (horizontal & vertical) ground motion records. We estimated the seismic losses with and without the vertical ground motion using a component‐based loss estimation approach based on FEMA‐P58. We also explored the sensitivity of the loss estimates to the characteristics of the input vertical acceleration fragility curves. Analysis results indicate a modest increase in the average annual losses (AAL) when the vertical component is included, consistent with the relatively small fraction of the total building replacement cost assigned to components sensitive to vertical motion. We also investigate the sensitivity of the loss estimates to the conditioning ground motion intensity measure adopted in the risk assessment procedure. Considerable discrepancies are observed in the loss estimates on an intensity basis and, to a lesser degree, on a risk basis. Among the tested intensity measures, average spectral acceleration performs better than single‐period spectral accelerations in two regards: it provides higher efficiency, and it maintains good consistency of the selected records with the site hazard while using lower levels of ground motion amplitude scaling. Whereas single‐period spectral ordinates that will approximate these advantages may exist, finding them requires some investigation.
Through several pathological mechanisms, chronic stress contributes to the development of “osteosarcopenic obesity”, a clinical syndrome that includes impairments in the structure and function of a patient’s bones, skeletal muscles, and adipose tissue. This syndrome, which could be alternatively called “chronic stress and inflammation syndrome”, has its genesis in early life and, by the age of 50–60 years, affects up to two-thirds of Western populations. Chronic psycho-socioeconomic stress and lifestyle factors, such as a sedentary life, poor quality nutrition, irregular daily schedules, and inadequate sleep, which all act on a genetic and epigenetic predisposition background, play essential pathogenic roles in the development of this widespread syndrome. Key pathogenic mediators are those of the stress system and inflammatory reaction. Lifestyle changes, in combination with stress management, can prevent, arrest, or reverse this debilitating syndrome.
