A pilot study of inexpensive sleep-assessment devices

Polysomnography (PSG), the gold standard sleep-assessment methodology, is impractical for many applications. Although alternative assessment methodologies are available, it is not clear which most correlates with PSG measures. This study compared sleep log (SL), actigraphy (ACT), and the REMview (RV) device for estimating PSG sleep measures. Thirty-three participants with various sleep-disorder diagnoses underwent 1 night of monitoring with PSG, RV, ACT, and SL. RV provided accurate estimates of most sleep variables. The accuracy of ACT and SL estimates depended on the sleep variable. These findings indicate that the selection of an alternative methodology should consider the sleep measure of interest in addition to the relative merits and drawbacks of each device.     

Clinical application of genetic risk assessment strategies for coronary artery disease: genotypes, phenotypes, and family history

Individuals with genetic predisposition to atherosclerosis have an increased risk for developing coronary artery disease (CAD), especially at young ages. They may derive the greatest benefit from traditional preventive strategies and strategies targeting novel,emerging risk factors. Because CAD is a complex, multifactorial disorder, global risk assessment has been recognized as an effective approach in preventing CAD and its manifestations. The systematic collection and interpretation of family history information is currently the most appropriate screening approach to identify individuals with genetic susceptibility to CAD. Much of the familial aggregation of CAD might be explained by familial aggregation of established risk factors and emerging CAD risk factors. Tests to assess genetic risk for CAD are primarily biochemical analyses that measure the different pathways involved in development and progression of disease. Some of these can guide and explain responses to treatment.     

NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdala

We examined the contribution of N-methyl-D-aspartate (NMDA) receptors (NMDARs) to the acquisition and expression of amygdaloid plasticity and Pavlovian fear conditioning using single-unit recording techniques in behaving rats. We demonstrate that NMDARs are essential for the acquisition of both behavioral and neuronal correlates of conditional fear, but play a comparatively limited role in their expression. Administration of the competitive NMDAR antagonist +/--3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) prior to auditory fear conditioning completely abolished the acquisition of conditional freezing and conditional single-unit activity in the lateral amygdala (LA). In contrast, CPP given prior to extinction testing did not affect the expression of conditional single-unit activity in LA, despite producing deficits in conditional freezing. Administration of CPP also blocked the induction of long-term potentiation in the amygdala. Together, these data suggest that NMDARs are essential for the acquisition of conditioning-related plasticity in the amygdala, and that NMDARs are more critical for regulating synaptic plasticity and learning than routine synaptic transmission in the circuitry supporting fear conditioning.     

Stem cell-mediated tolerance inducing strategies in organ transplantation

The scope of possible tools to modulate the recipients immune response towards tolerance induction basically includes deletional and non deletional mechanisms, which are currently targeted by various strategies including monoclonal antibodies, cytokine deviation, chimerism induction and the support of regulating T-cells. Here we summarize the main findings in the field derived from experimental animal studies and currently performed clinical studies. This review focuses to give a clinically relevant overview over relevant tolerance inducing concepts, taking into consideration risk profiles and clinical efficacy associated with specific immunosuppressive regiments currently applied in the clinical setting of transplantation.     

Tolerance-inducing strategies in transplantation surgery—current status and perspectives

Background Life-long immunosuppressive medication has to be administered to the majority of solid-organ recipients after transplantation of genetically mismatched organs in order to circumvent acute graft loss due to alloreactive rejection responses triggered by the host's immune system. However, life-long suppression of the immune system implicitly limits the host's ability to respond appropriately to infectious, fungal and carcinogenic threats. Simultaneously non-targeted inhibition of immunological defense mechanisms coincides with substantial morbidity and mortality for the host. Thus, for the past five decades research in the field of transplantation medicine has focused on innovative strategies to induce graft tolerance to donor alloantigens, a state in which the recipient's lymphocytes have learned to accept the foreign organ or tissue as "self" or "non-dangerous" without the need of chronic immunosuppression. Achieving that specific goal of donor-specific tolerance would not only minimize the risk of the recipient to suffer from serious side effects resulting from continuous immunosuppressive therapy, but would also prevent loss of long-term graft function caused by chronic rejection processes. Recently, numerous insights into the dynamic interrelationships of host immune responses elicited by donor antigen-presentation, either on the graft itself or on specialized antigen-presenting cells, have substantially broadened our understanding of the cascade of events that result in the acquisition of tolerance.Method We highlight areas of research that are currently particularly helpful not only to set up new strategies to induce donor-specific tolerance or long-term graft acceptance, but also to identify and describe parameters which serve to characterize those patients who have acquired a state of tolerance and are safe to be weaned off from their immunosuppressive regimen.     

Oral glucose before venepuncture relieves neonates of pain, but stress is still evidenced by increase in oxygen consumption, energy expenditure, and heart rate

Oral glucose was recommended as pain therapy during venepuncture in neonates. It is unclear whether this intervention reduces excess oxygen consumption (o(2)), energy loss, or cardiovascular destabilization associated with venepuncture, and whether <2 mL glucose solution is effective. We tested the hypothesis that oral glucose solution attenuates the increases in neonatal oxygen consumption, energy expenditure (EE), and heart rate associated with venepuncture for two different volumes of glucose solution (2 and 0.4 mL). In this prospective, randomized, controlled, double-blind trial, 58 neonates (gestational age, 31-42 wk; postnatal age, 1-7 d) were randomized to 2 mL glucose 30%, 0.4 mL glucose 30%, or 2 mL water by mouth before venepuncture. The videotaped behavioral pain reactions were scored with the Premature Infant Pain Profile. Cry duration, o(2), EE (indirect calorimetry), and heart rate were measured. The 2 mL glucose solution reduced pain score and crying after venepuncture compared with controls [median pain score, 5.5 (interquartile range, 4-9) versus 11 (7-12), p = 0.01; median duration of first cry, 0 s (0-43 s) versus 13 s (2-47 s), p < 0.05, respectively]. The 0.4 mL glucose solution had no effect. The 2 mL glucose solution did not attenuate the o(2) increase during venepuncture (1.5 +/- 0.2 mL/kg min (water) versus 1.7 +/- 0.5 (0.4 mL glucose) versus 1.1 +/- 0.2 (2 mL glucose) (mean +/- SEM) nor EE nor heart rate. We conclude that oral administration of 2 mL glucose 30% before venepuncture reduced pain expression and crying, but did not prevent the rise in o(2), EE, or heart rate. Alternative therapies against the stress of nonpainful handling during venepuncture should be explored.     

Auditory fear conditioning increases CS-elicited spike firing in lateral amygdala neurons even after extensive overtraining

We examined the influence of extensive overtraining (75 trials) of auditory fear conditioning on the expression of conditional stimulus (CS)-elicited spike firing in lateral amygdala (LA) neurons. Single units were recorded from chronic multichannel electrodes implanted in the LA of conscious and freely moving rats. In sequential training sessions, the rats received either five or 70 fear conditioning trials, which consisted of a white-noise CS and a coterminating footshock unconditional stimulus (US). Unpaired (sensitization) controls received the same number of trials, but the CS and US were explicitly unpaired. Paired CS-US presentations yielded robust increases in CS-elicited spike firing in LA neurons after both five and 70 conditioning trials, and the magnitude of the spike firing increases was correlated with the expression of conditional freezing to the CS. After 75 training trials, maximal conditioning-related increases in LA firing were exhibited within 20 ms of CS onset, indicating that this increase is mediated by direct thalamo-amygdala projections. There was no significant increase in CS-elicited spike firing or freezing behaviour in the unpaired group. These results complement amygdala lesion studies [e.g. Maren, S. (1999a) J. Neurosci., 19, 8696-8703] and support the view that the basolateral complex of the amygdala is involved in the encoding and storage of fear memories even after extensive overtraining.