Business-centric data solutions for safeguarding animal agriculture in the United States of America.

Business-centric solutions to data-related problems often yield the greatest positive impacts and improvements for private enterprises but are challenging to design and implement at scale within government agencies. The core mission of the Veterinary Services of the United States Department of Agriculture (USDA) Animal Plant Health Inspection Service is to safeguard animal agriculture in the United States of America, and effective data management underpins these efforts. As this agency works to assist data-driven decision-making in animal health management, it continues to use a blend of best practices from Federal Data Strategy initiatives and the International Data Management Association framework. This paper describes three case studies that focus on strategies to improve animal health data collection, integration, reporting and governance for animal health authorities. These strategies have enhanced the way USDA's Veterinary Services execute their mission and core operational activities for prevention, detection and early response to support disease containment and control.

S'agissant des problèmes en lien avec les données, les solutions centrées sur l'activité sont souvent celles qui génèrent le plus d'effets positifs et d'améliorations pour les entreprises du secteur privé, mais elles sont difficiles à concevoir et à mettre en oeuvre à grande échelle au sein des agences gouvernementales. Les Services vétérinaires du Service d'inspection de la santé animale et végétale du département américain de l'Agriculture (USDA) ont pour mission centrale de préserver les productions animales états-uniennes ; une gestion efficace des données vient soutenir cet effort. Dans leur action d'appui aux processus décisionnels de gestion de la santé animale fondés sur les données, ces Services recourent à une combinaison de bonnes pratiques mises en oeuvre aussi bien par les initiatives de la Stratégie fédérale sur les données que dans le cadre de l'Association internationale de gestion des données. Les auteurs décrivent trois études de cas sur des stratégies visant à améliorer la collecte, l'intégration, la notification et la gouvernance des données de santé animale afin de répondre aux besoins des autorités compétentes dans ce domaine. Ces stratégies ont permis aux Services vétérinaires de l'USDA de mieux s'acquitter de leur mission et d'améliorer leurs activités opérationnelles de prévention, de détection et de réaction rapide afin d'endiguer et contrôler les maladies.

Las soluciones eminentemente empresariales a problemas relacionados con los datos deparan con frecuencia los mejores frutos y resultados a la empresa privada, pero son difíciles de diseñar y aplicar a escala dentro de las administraciones públicas. Los Servicios Veterinarios adscritos al Servicio de Inspección Sanitaria de Animales y Plantas del Departamento de Agricultura de los Estados Unidos (USDA) tienen por principal cometido salvaguardar la producción animal estadounidense, labor que pasa en parte por una eficaz gestión de los datos. En su función de apoyo a la adopción de decisiones de gestión zoosanitaria basadas en los datos, este organismo sigue empleando una combinación de prácticas óptimas tomadas de iniciativas de la Estrategia Federal de Datos y de las pautas marcadas por la Asociación Internacional de Gestión de Datos. Los autores presentan y analizan tres ejemplos de estrategias para mejorar la obtención, integración, notificación y administración de datos zoosanitarios para las autoridades del ramo. Estas estrategias han conferido mayor eficacia a los Servicios Veterinarios del USDA en el cumplimiento de su misión y en la ejecución de sus principales actividades operativas de prevención, detección y pronta respuesta para ayudar a contener y combatir enfermedades.

Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men.

CONTEXT: Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link. OBJECTIVE: Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations. METHODS: Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales. RESULTS: Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol. CONCLUSION: The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.

[Current developments in measuring quality of life with instruments of the European organisation for research and treatment of cancer (EORTC)]. / Aktuelle Entwicklungen bei der Erfassung der Lebensqualität mit Instrumenten der European Organisation for Research and Treatment of Cancer (EORTC).

Since many years, the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group develops and validates measures for the assessment of quality of life in cancer patients, using high standards of methodology. These questionnaires are meant to be used primarily in clinical trials.As treatment strategies are changing and because of some -methodological criticism, the head and neck module EORTC QLQ-H&N35 is currently being revised and updated.In this paper, we will present the current state of work and other recent developments regarding the EORTC Quality of Life questionnaire development.

The brain H3-receptor as a novel therapeutic target for vigilance and sleep-wake disorders.

Brain histaminergic neurons play a prominent role in arousal and maintenance of wakefulness (W). H(3)-receptors control the activity of histaminergic neurons through presynaptic autoinhibition. The role of H(3)-receptor antagonists/inverse agonists (H(3)R-antagonists) in the potential therapy of vigilance deficiency and sleep-wake disorders were studied by assessing their effects on the mouse cortical EEG and sleep-wake cycle in comparison to modafinil and classical psychostimulants. The H(3)R-antagonists, thioperamide and ciproxifan increased W and cortical EEG fast rhythms and, like modafinil, but unlike amphetamine and caffeine, their waking effects were not accompanied by sleep rebound. Conversely, imetit (H(3)R-agonist) enhanced slow wave sleep and dose-dependently attenuated ciproxifan-induced W, indicating that the effects of both ligands involve H(3)-receptor mechanisms. Additional studies using knockout (KO) mice confirmed the essential role of H(3)-receptors and histamine-mediated transmission in the wake properties of H(3)R-antagonists. Thus ciproxifan produced no increase in W in either histidine-decarboxylase (HDC, histamine-synthesizing enzyme) or H(1)- or H(3)-receptor KO-mice whereas its waking effects persisted in H(2)-receptor KO-mice. These data validate the hypothesis that H(3)R-antagonists, through disinhibition of H(3)-autoreceptors, enhancing synaptic histamine that in turn activates postsynaptic H(1)-receptors promoting W. Interestingly amphetamine and modafinil, despite their potent arousal effects, appear unlikely to depend on histaminergic mechanism as their effects still occurred in HDC KO-mice. The present study thus distinguishes two classes of wake-improving agents: the first acting through non-histaminergic mechanisms and the second acting via histamine and supports brain H(3)-receptors as potentially novel therapeutic targets for vigilance and sleep-wake disorders.

[Impact of sleep debt on physiological rhythms]. / Impact d'une dette de sommeil sur les rythmes physiologiques.

Sleep loss due to voluntary bedtime curtailment has become a hallmark of modern society. Even though sleep deprivation in rodents has been shown to result in death, it was until a few years ago thought that sleep loss results in increased sleepiness and decreased cognitive performance but has little or no adverse effects on human health. We measured sleep and 24-hour hormonal profiles in 11 healthy young males after 6 days of sleep restriction (4-hour bedtime) and after 6 days of sleep recovery (12-hour bedtime). At the end of sleep restriction, we observed reduced amounts of slow wave sleep (SWS) and rapid eye movement (REM) sleep and an alteration in the temporal distribution of these sleep stages, i.e. an increased pressure for REM sleep at the beginning of the sleep period and a decrease in the amount of slow wave activity (SWA) during the first sleep cycle. These later abnormalities are usually observed in depression. In addition, numerous alterations in the 24-hour hormonal profiles were observed in the state of sleep debt. The amount of melatonin secreted was reduced because of a delay in the onset of the nocturnal secretion and a reduction in the value of the acrophase. If the overall 24-hour cortisol profile was preserved, sleep restriction was associated with increased cortisol levels in late afternoon and evening hours and the duration of the quiescent period was reduced. The 24-hour mean TSH levels were reduced and the nocturnal TSH elevation was markedly dampened, most likely as a result of elevated levels of thyroid hormones. The acrophase of the 24-hour leptin profile occurred earlier, the amplitude of the rhythm and the overall mean levels were reduced. The nocturnal elevation of prolactin levels was abrupt but of short duration and the 24-hour mean levels were decreased. A pulse of growth hormone occurred prior to sleep onset, therefore affecting SWA distribution at the beginning of the sleep period. Since these alterations are qualitatively and quantitatively similar to those observed during aging and sometimes during depression, a state of sleep debt, as is experienced by a substantial fragment of the population in modern societies, is likely to increase the severity of depression and widespread age-related chronic conditions such as obesity, diabetes and hypertension.

Analysis of fatty acid ethyl esters in hair as possible markers of chronically elevated alcohol consumption by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS).

Fatty acid ethyl esters (FAEE) are products of the nonoxidative ethanol metabolism, which are known to be detectable in blood only about 24h after the last alcohol intake. After deposition in hair they should be suitable long-term markers of chronically elevated alcohol consumption. Therefore, a method for the analysis of ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate from hair was developed based on the extraction of the hair sample by a dimethylsulphoxide (DMSO)/n-hexane mixture, separation and evaporation of the n-hexane phase and application of headspace solid-phase microextraction (HS-SPME) in combination with gas chromatography-mass spectrometry (GC-MS) to the extract. For use as internal standards, the corresponding D(5)-ethyl esters were prepared. The HS-SPME/GC-MS measurements were automatically performed using a multi-purpose sampler. The detection limits of the FAEE were between 0.01 and 0.04ng/mg and the reproducibility was between 3.5 and 16%. By application of the method to hair samples of 21 fatalities with known heavy alcohol abuse 0.045-2.4ng/mg ethyl myristate, 0.35-13.5ng/mg ethyl palmitate, 0.25-7.7ng/mg ethyl oleate and 0.05-3.85ng/mg ethyl stearate were measured. For social drinkers (30-60g ethanol per week), the concentrations were about one order of magnitude smaller. For 10 teetotalers negative results or traces of ethyl palmitate were found. It was shown by supplementary investigations in single cases that FAEE are also present in sebum, that there is no strong difference in their concentrations between pubic, chest and scalp hair, and that they are detectable in hair segments after a 2 months period of abstinence. From the results follows that the measurement of FAEE concentrations in hair is a useful way for a retrospective detection of alcohol abuse.

On the similarity of properties in solution or in the crystalline state: a molecular dynamics study of hen lysozyme.

As protein crystals generally possess a high water content, it is assumed that the behaviour of a protein in solution and in crystal environment is very similar. This assumption can be investigated by molecular dynamics (MD) simulation of proteins in the different environments. Two 2ns simulations of hen egg white lysozyme (HEWL) in crystal and solution environment are compared to one another and to experimental data derived from both X-ray and NMR experiments, such as crystallographic B-factors, NOE atom-atom distance bounds, 3J(H N alpha)-coupling constants, and 1H-15N bond vector order parameters. Both MD simulations give very similar results. The crystal simulation reproduces X-ray and NMR data slightly better than the solution simulation.

Adaptation of the 24-h growth hormone profile to a state of sleep debt.

In normal men, the majority of GH secretion occurs in a single large postsleep onset pulse that is suppressed during total sleep deprivation. We examined the impact of semichronic partial sleep loss, a highly prevalent condition, on the 24-h growth hormone profile. Eleven young men were studied after six nights of restricted bedtimes (0100-0500) and after 7 nights of extended bedtimes (2100-0900). Slow-wave sleep (SWS) was estimated as the duration of stages III and IV. Slow-wave activity (SWA) was calculated as electroencephalogram power density in the 0.5- to 3-Hz frequency range. During the state of sleep debt, the GH secretory pattern was biphasic, with both a presleep onset "circadian" pulse and a postsleep onset pulse. Postsleep onset GH secretion was negatively related to presleep onset secretion and tended to be positively correlated with the amount of concomitant SWA. When sleep was restricted, both SWS and SWA were increased during early sleep. Unexpectedly, the increase in SWA affected the second, rather than the first, SWA cycle, suggesting that presleep onset GH secretion may have limited SWA in the first cycle, possibly via an inhibition of central GH-releasing hormone activity. Thus neither the GH profile nor the distribution of SWA conformed with predictions from acute sleep deprivation studies, indicating that adaptation mechanisms are operative during chronic partial sleep loss.

Doxepin toxicity in a child following topical administration.

OBJECTIVE: To describe a case of a child with altered mental status following the topical administration of doxepin. CASE SUMMARY: A five-year-old Hispanic girl was brought to the emergency department because she was difficult to arouse at school. She had recently developed a generalized eczematous rash for which she was prescribed doxepin hydrochloride 5% cream. An entire tube (30 g) of doxepin cream was applied in the 24 hours prior to presentation. The patient was responsive only to noxious stimuli, with no focal neurologic abnormalities. She was decontaminated and observed in a pediatric intensive care unit. By 18 hours after presentation, she had fully recovered and was discharged. CONCLUSIONS: Topical doxepin, available as a 5% cream, is indicated for the treatment of pruritus secondary to eczematous dermatoses in adults. Diminished skin integrity and the application of a massive quantity of doxepin 5% cream to a large body surface area contributed to the toxicity in this child. Since the safety and efficacy of doxepin cream has not been established in children younger than 12 years, it should be used with caution in this population.

The role of complement in Alzheimer's disease pathology.

Complement proteins are integral components of amyloid plaques and cerebral vascular amyloid in Alzheimer brains. They can be found at the earliest stages of amyloid deposition and their activation coincides with the clinical expression of Alzheimer's dementia. This review will examine the origins of complement in the brain and the role of beta-amyloid peptide (Abeta) in complement activation in Alzheimer's disease, an event that might serve as a nidus of chronic inflammation. Pharmacology therapies that may serve to inhibit Abeta-mediated complement activation will also be discussed.

Traumatic brain injury elevates the Alzheimer's amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury.

The increased risk for Alzheimer's Disease (AD) associated with traumatic brain injury (TBI) suggests that environmental insults may influence the development of this age-related dementia. Recently, we have shown that the levels of the beta-amyloid peptide (A beta 1-42) increase in the cerebrospinal fluid (CSF) of patients after severe brain injury and remain elevated for some time after the initial event. The relationships of elevated A beta with markers of blood-brain barrier (BBB) disruption, inflammation, and nerve cell or axonal injury were evaluated in CSF samples taken daily from TBI patients. This analysis reveals that the rise in A beta 1-42 is best correlated with possible markers of neuronal or axonal injury, the cytoskeletal protein tau, neuron-specific enolase (NSE), and apolipoprotein E (ApoE). Similar or better correlations were observed between A beta 1-40 and the three aforementioned markers. These results imply that the degree of brain injury may play a decisive role in determining the levels of A beta 1-42 and A beta 1-40 in the CSF of TBI patients. Inflammation and alterations in BBB may play lesser, but nonetheless significant, roles in determining the A beta level in CSF after brain injury.

CI-1017, a functionally M1-selective muscarinic agonist: design, synthesis, and preclinical pharmacology.

The five muscarinic receptor subtypes (M1-M5) are characterized by seven helices that define a transmembrane cavity which serves as the binding pocket for agonists and antagonists. The five cavities appear to be topographically different enough to permit subtype selectivity among antagonists but not among classical agonists which tend to be smaller in size than antagonists. It was reasoned that synthesis of muscarinic agonists longer/larger than their classical counterparts might result in subtype selectivity. M1 subtype selectivity was found in a class of 1-azabicyclo[2.2.1]heptan-3-one, O-(3-aryl-2-propynyl) oximes. One of these, CI-1017, improved spatial memory of hippocampally deficient mice and nbM-lesioned rats at doses of 1.0-3.2 and 0.1-0.3 mg/kg, respectively, while producing parasympathetic side effects only at very high doses (100-178 mg/kg). Additionally, CI-1017 inhibited production of amyloidogenic A beta and increased secretion of soluble APP. Thus, CI-1017, besides treating AD symptomatically, may also retard its progression. CI-1017 has recently completed phase I clinical trials.

Pathophysiology of human circadian rhythms.

The 24 h profiles of hormonal secretions represent a good model for the study of the human circadian system. Diurnal hormonal variations generally reflect the modulation of ultradian or pulsatile release at 1-2 h intervals by signals occurring at nearly 24 h periods and result from the interaction of an internal timekeeping system--or circadian clock--with the sleep-wake homeostasis and various environmental factors, including the light-dark cycle, periodic changes in activity levels and the meal schedule. This temporal organization is altered in many pathophysiological conditions, including ageing, sleep loss, night or shift work, jet lag, affective disorders and endocrine diseases. Both photic and non-photic stimuli may affect the regulation of the circadian pacemaker and, therefore, the diurnal pattern of hormonal secretions. Appropriately timed stimuli may induce either a phase-advance or a phase-delay of the circadian clock, according to the timing of administration. Phase-shifting effects have been shown in humans for light and for dark pulses, physical exercise, melatonin and melatonin agonists, and benzodiazepine hypnotics. These results open new perspectives for the treatment of a variety of disorders involving dysregulation of the circadian rhythmicity.

The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease.

Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Abeta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Abeta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.

Are there possibilities for the detection of chronically elevated alcohol consumption by hair analysis? A report about the state of investigation.

The analysis of suitable ethanol markers in hair would be an advantageous tool for chronic alcohol abuse control because of the wide diagnostic window allowed by this specimen and the possibility of segmental investigation. Between the markers practically used or thoroughly investigated in blood or urine, ethylglucuronide, fatty acid ethylesters, phosphatidylethanol, acetaldehyde adducts to protein and 5-hydroxytryptophol can be regarded as possible candidates also in hair, but preliminary data were found in the literature only for ethylglucuronide and acetaldehyde modified proteins. By using headspace gas chromatography and headspace solid phase microextraction in combination with gas chromatography-mass spectrometry (SPME-GC/MS), in alkaline hydrolysates of hair it was possible to determine between 17 and 135 ng/mg of ethanol beside acetone and several other volatile compounds with slightly higher ethanol values for alcoholics than for social drinkers and teetotalers. A part of this is ethanol only absorbed in the hair matrix from the surrounding environment and consequently is not applicable as a diagnostic criterion. By extraction with aqueous buffer, methanol or a methanol/chloroform mixture and subsequent alkaline hydrolysis it was found that another part is generated from ethylesters, which are preferentially deposited in the lipid fraction of hair. In a specific search for ethylesters of 17 carboxylic acids by GC/MS-SIM in most cases ethyl 4-hydroxybenzoate (0.1 to 5.9 ng/mg, a preservative in hair cosmetics) and in four cases traces of indolylacetic acid ethylester were found. Furthermore, diethyl phthalate (a softening agent, present also in many cosmetic products) was identified in the hair of alcoholics as well as of children. As potential markers of alcohol intake, ethyl palmitate, ethyl stearate and ethyl oleate were detected in hair samples of alcoholics by headspace SPME-GC/MS of the chloroform/methanol extracts.

Impact of sleep debt on metabolic and endocrine function.

BACKGROUND: Chronic sleep debt is becoming increasingly common and affects millions of people in more-developed countries. Sleep debt is currently believed to have no adverse effect on health. We investigated the effect of sleep debt on metabolic and endocrine functions. METHODS: We assessed carbohydrate metabolism, thyrotropic function, activity of the hypothalamo-pituitary-adrenal axis, and sympathovagal balance in 11 young men after time in bed had been restricted to 4 h per night for 6 nights. We compared the sleep-debt condition with measurements taken at the end of a sleep-recovery period when participants were allowed 12 h in bed per night for 6 nights. FINDINGS: Glucose tolerance was lower in the sleep-debt condition than in the fully rested condition (p<0.02), as were thyrotropin concentrations (p<0.01). Evening cortisol concentrations were raised (p=0.0001) and activity of the sympathetic nervous system was increased in the sleep-debt condition (p<0.02). INTERPRETATION: Sleep debt has a harmful impact on carbohydrate metabolism and endocrine function. The effects are similar to those seen in normal ageing and, therefore, sleep debt may increase the severity of age-related chronic disorders.

Detection of 6-acetylmorphine in vitreous humor and cerebrospinal fluid--comparison with urinary analysis for proving heroin administration in opiate fatalities.

The concentrations of morphine and 6-acetylmorphine (6-AM) in urine, cerebrospinal fluid (CSF), and vitreous humor (VH) and the morphine concentrations in blood were determined by gas chromatography-mass spectrometry for 29 fatalities after abuse of heroin either alone or in combination with alcohol and other drugs. 6-AM was found above a quantitation limit of 1 ng/mL in urine in 89% of the cases, in CSF in 68% of the cases, and in VH in 75% of the cases. The 6-AM concentrations in CSF (mean, 10 ng/mL) and VH (mean, 17 ng/mL) were in general much smaller than in urine (mean, 170 ng/mL); therefore, the different pharmacokinetic behavior of the fluids is discussed. There is no uniformity between the three fluids with respect to the presence or absence of 6-AM. Therefore, CSF or VH may be used as complementary or alternative materials to urine in order to prove heroin uptake in opiate fatalities.

Lactoferrin increases the output of neutrophil precursors and attenuates the spontaneous production of TNF-alpha and IL-6 by peripheral blood cells.

The aim of this report was to investigate the effects of bovine lactoferrin (BLF) taken orally (per os) by healthy individuals, on selected immune parameters. Three groups of volunteers (7 persons per group) were taken daily for 7 days, one capsule containing 2, 10 or 50 mg of BLF. A control group has taken placebo only. Venous blood was taken for tests a few hours before the first dose of BLF, one day and 14 days after the last dose of the preparation. For the evaluation of BLF action on the immune response system we have chosen 3 parameters: content of neutrophil precursors in the peripheral blood (in percentage), spontaneous production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) by unstimulated blood cell cultures. We found that oral treatment of volunteers with BLF caused a transient (one day after last dose) increase of immature forms of neutrophils in the circulating blood. That increase was more than 2-fold in the case of 10 mg dose. However, statistically significant increases in the percentage of neutrophil precursors were also registered at doses of 2 and 50 mg of BLF. No change in the immature cell content was observed in the placebo group. The treatment with BLF also resulted in a profound decrease of the spontaneous production of IL-6 and TNF-alpha by cultures of peripheral blood cells. This decrease was significant (10 mg/dose) one day following the last dose of BLF and persisted for additional 14 days. These results confirmed our earlier data on the effects of per os treatment with a nutritional preparation containing BLF. Furthermore, we were able to closer establish the optimal dose of BLF affecting selected immune indices.

Sleep as a mediator of the relationship between socioeconomic status and health: a hypothesis.

This article discusses the hypothesis that the adverse impact of low socioeconomic status (SES) on health may be partly mediated by decrements in sleep duration and quality. Low SES is frequently associated with a diminished opportunity to obtain sufficient sleep or with environmental conditions that compromise sleep quality. In a recent study, we examined carbohydrate metabolism, endocrine function, and sympatho-vagal balance in young, healthy adults studied after restricting sleep to four hours per night for six nights as compared to a fully rested condition obtained by extending the bed-time period to 12 hours per night for six nights. The state of sleep debt was associated with decreased glucose tolerance, elevated evening cortisol levels, and increased sympathetic activity. The alterations in glucose tolerance and hypothalamo-pituitary-adrenal function were qualitatively and quantitatively similar to those observed in normal aging. These results indicate that sleep loss can increase the "allostatic load" and facilitate the development of chronic conditions, such as obesity, diabetes, and hypertension, which have an increased prevalence in low SES groups.