Use of the hydantoin isostere to produce inhibitors showing selectivity toward the vesicular glutamate transporter versus the obligate exchange transporter system x(c)(-).

Evidence was acquired prior to suggest that the vesicular glutamate transporter (VGLUT) but not other glutamate transporters were inhibited by structures containing a weakly basic α-amino group. To test this hypothesis, a series of analogs using a hydantoin (pK(a)∼9.1) isostere were synthesized and analyzed as inhibitors of VGLUT and the obligate cystine-glutamate transporter (system x(c)(-)). Of the hydantoin analogs tested, a thiophene-5-carboxaldehyde analog 2l and a bis-hydantoin 4b were relatively strong inhibitors of VGLUT reducing uptake to less than 6% of control at 5mM but few inhibited system x(c)(-) greater than 50% of control. The benzene-2,4-disulfonic acid analog 2b and p-diaminobenzene analog 2e were also good hydantoin-based inhibitors of VGLUT reducing uptake by 11% and 23% of control, respectively, but neither analog was effective as a system x(c)(-) inhibitor. In sum, a hydantoin isostere adds the requisite chemical properties needed to produce selective inhibitors of VGLUT.

Binge drinking and insomnia in students from health sciences at one university in Rio de Janeiro, Brazil.

In spite of the many studies examining alcohol consumption, recent reviews have indicated that binge drinking has not been extensively studied. Furthermore, it is becoming increasingly clear that sleep is associated with many physiological functions and to drug addictions. The present study aimed to evaluate the relationship between alcohol binge drinking and insomnia in college students of health sciences. All first-year health sciences students (n=286) were evaluated in a cross-sectional study. Envelopes containing the Insomnia Severity Index (ISI), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and questions capturing sociodemographic data were distributed and collected in classes. It was found that most non-drinkers were female (70.6%), although there were no sex-related differences in the number of binge drinkers (more than 5 drinks on each occasion at least once a week), allowing statistical comparison. The Mann-Whitney U test indicated that the ISI scores were significantly greater in female than male binge drinkers (P=0.014). Moderate or severe insomnia was reported by 23% of the sample, with alcohol being the most frequently associated substance. A specialized intervention was suggested by ASSIST: brief for marijuana (19.2%) and tobacco (23.3%) use, and moderate (31.5%) or intensive (1.4%) for alcohol consumers. The data highlighted the need to pay attention to the habits of college students beyond obtaining scientific information. New data suggesting the influence of genetics on insomnia may be of importance when performing additional studies on the sex differences in alcohol binge drinking.

Conformationally-restricted amino acid analogues bearing a distal sulfonic acid show selective inhibition of system x(c)(-) over the vesicular glutamate transporter.

A panel of amino acid analogs and conformationally-restricted amino acids bearing a sulfonic acid were synthesized and tested for their ability to preferentially inhibit the obligate cysteine-glutamate transporter system x(c)(-) versus the vesicular glutamate transporter (VGLUT). Several promising candidate molecules were identified: R/S-4-[4'-carboxyphenyl]-phenylglycine, a biphenyl substituted analog of 4-carboxyphenylglycine and 2-thiopheneglycine-5-sulfonic acid both of which reduced glutamate uptake at system x(c)(-) by 70-75% while having modest to no effect on glutamate uptake at VGLUT.

Anxiety and cardiovascular symptoms: the modulating role of insomnia.

BACKGROUND: Anxiety and insomnia are associated with cardiovascular (CV) symptoms. We assessed whether the relation between anxiety and CV symptoms is modulated by insomnia. METHODS: Independently living women (n = 1,440; mean age = 59.36 +/- 6.53 years) were recruited by cluster sampling technique. We obtained data on demographic characteristics, health beliefs, access to health care, CV symptoms, sleep, stress and anxiety levels. RESULTS: Overall, 56% of the sample reported insomnia; 46% reported CV symptoms, and 54% were highly anxious. There was a greater likelihood for highly anxious women and those experiencing insomnia to report CV symptoms (r(s) = 0.31* and r(s) = 0.32*, respectively). In logistic regression analysis, the adjusted odds ratios for reporting CV symptoms were 1.39 for patients with insomnia and 2.79 for those with anxiety. With control for insomnia, we observed a 3-fold reduction in the magnitude of the association between anxiety and CV symptoms (r(p) = 0.09*). Stepwise adjustments for sociodemographic factors, CV risk markers, and factors anchoring health beliefs and access to health care showed lesser impact on the relationships. With simultaneous control for those covariates, the correlation was r(p) = 0.13*; * p < 0.01. CONCLUSION: The association of CV symptoms with anxiety is partly accounted for by insomnia.

Perceived insomnia, anxiety, and depression among older Russian immigrants.

There are few data on the relationships of anxiety and depression to insomnia among immigrants in the United States. Observations of high rates of symptoms of these associated conditions among older Russians indicate the need to focus clinical attention on this population. Relationships of self-reported depression and anxiety to insomnia complaints were investigated in a community-based sample of older Russian immigrants. Volunteers (N=307) were urban community-residing Russians (ages 50 to 95 years; 54% women). Surveys were conducted in a semistructured environment by bilingual educators in various community centers. 93% reported a major health problem, 83% experienced pain, and 62% had problems engaging in daily activities. Of the sample, 61% reported an insomnia complaint, and 43% considered depression and/or anxiety to be a major impairment. Logistic regression analysis showed that insomnia was the most important predictor of perceived anxiety and depression; the corresponding multivariate-adjusted odds ratio was 4.37. Insomnia complaints and perceptions of depression and anxiety among older Russians may have a synergistic effect. Both patients and primary-care physicians should be better educated regarding the recognition of barriers limiting access to adequate health care among older Russians.

Obstructive sleep apnea, cognition and Alzheimer's disease: A systematic review integrating three decades of multidisciplinary research.

Increasing evidence links cognitive-decline and Alzheimer's disease (AD) to various sleep disorders, including obstructive sleep apnea (OSA). With increasing age, there are substantial differences in OSA's prevalence, associated comorbidities and phenotypic presentation. An important question for sleep and AD researchers is whether OSA's heterogeneity results in varying cognitive-outcomes in older-adults compared to middle-aged adults. In this review, we systematically integrated research examining OSA and cognition, mild cognitive-impairment (MCI) and AD/AD biomarkers; including the effects of continuous positive airway pressure (CPAP) treatment, particularly focusing on characterizing the heterogeneity of OSA and its cognitive-outcomes. Broadly, in middle-aged adults, OSA is often associated with mild impairment in attention, memory and executive function. In older-adults, OSA is not associated with any particular pattern of cognitive-impairment at cross-section; however, OSA is associated with the development of MCI or AD with symptomatic patients who have a higher likelihood of associated disturbed sleep/cognitive-impairment driving these findings. CPAP treatment may be effective in improving cognition in OSA patients with AD. Recent trends demonstrate links between OSA and AD-biomarkers of neurodegeneration across all age-groups. These distinct patterns provide the foundation for envisioning better characterization of OSA and the need for more sensitive/novel sleep-dependent cognitive assessments to assess OSA-related cognitive-impairment.

Unexpected Formation of Highly Functionalized Dihydropyrans via Addition-Cyclization Reactions Between Dimethyl Oxoglutaconate and α,ß-Unsaturated Hydrazones.

The condensation between dienophiles and α,ß-unsaturated hydrazone azadienes was previously reported to afford piperidines. During an attempt to adapt this reaction to the preparation of piperidine-based conformationally-restricted analogs of glutamate, it was discovered that the electrophile, dimethyl oxoglutaconate (DOG) led to highly substituted dihydropyrans in 20-50% yield. The unexpected pyran product likely results from an initial 1,4-addition of the hydrazone to the oxoglutaconate followed by intramolecular cyclization of the resultant enolate oxygen to the α,ß-unsaturated iminium ion. Further manipulations afford substituted tetrahydropyran 6-methamino-2,4-dicarboxylic acids.

Obstructive sleep apnea and cardiovascular disease: evidence and underlying mechanisms.

A body of epidemiologic and clinical evidence dating back to the early 1960s establishes the relationships between sleep apnea and cardiovascular disease (CVD). Individuals with obstructive sleep apnea, the most common type of sleep-disordered breathing, are at increased risk for coronary artery disease, congestive heart failure, and stroke. Evidence that treatment of sleep apnea with continuous positive airway pressure reduces blood pressure, improves left ventricular systolic function, and diminishes platelet activation further supports linkage between obstructive sleep apnea and CVD. Notwithstanding, complex associations between these two conditions remain largely unexplained due to dearth of systematic experimental studies. Arguably, several intermediary mechanisms including sustained sympathetic activation, intrathoracic pressure changes, and oxidative stress might be involved. Other abnormalities such as dysfunctions in coagulation factors, endothelial damage, platelet activation, and increased systemic inflammation might also play a fundamental role. This review examines evidence for the associations between obstructive sleep apnea and CVD and suggested underlying anatomical and physiological mechanisms. Specific issues pertaining to definition, prevalence, diagnosis, and treatment of sleep apnea are also discussed. Consistent with rising interest in the potential role of the metabolic syndrome, this review explores the hypothesized mediating effects of each of the components of the metabolic syndrome.

Uncontrolled blood pressure and risk of sleep apnea among blacks: findings from the Metabolic Syndrome Outcome (MetSO) study.

Uncontrolled blood pressure (BP) is linked to increased risk of obstructive sleep apnea (OSA). However, few studies have assessed the impact of this relationship among blacks with metabolic syndrome (MetS). Data for this study were collected from 1035 blacks (mean age=62±13 years) enrolled in the Metabolic Syndrome Outcome study. Patients with a score ⩾6 on the Apnea Risk Evaluation System were considered at risk for OSA. Of the sample, 77.1% were low-to-high OSA risk and 92.3% were hypertensive, of which 16.8% had uncontrolled BP levels. Analysis also showed that 60.4% were diabetic, 8.9% had a stroke history, 74.3% had dyslipidemia, 69.8% were obese and 30.9% had a history of heart disease. Logistic regression analyses were employed to investigate associations between uncontrolled BP and OSA risk, while adjusting for known covariates. Findings showed that uncontrolled BP independently increased the odds of OSA risk twofold (odds ratio=2.02, 95% confidence interval=1.18-3.48, P<0.05). In conclusion, our findings show that uncontrolled BP was associated with a twofold greater risk of OSA among blacks, suggesting that those with MetS and who have uncontrolled BP should be screened for the presence of OSA.

I sleep, because we sleep: a synthesis on the role of culture in sleep behavior research.

AIM: The aim of this study was to synthesize the literature on the cultural aspects of sleep and their relevance to behavioral sleep research. METHODS: A narrative synthesis of the existing literature on sleep was conducted with a focus on its biological, sociological, political, and anthropological aspects. This synthesis was guided by the PEN-3 cultural model, developed by the primary author. RESULTS: The findings highlight the cross-cultural contexts within which people sleep and the role of varied sleeping arrangements in influencing sleep behavior and perspectives. Furthermore, the contexts in which sleep occurs, coupled with the influence of the family, and the positive aspects of sleep helped illustrate why cultural aspects of sleep are vital for a broader understanding of sleep. DISCUSSION: The authors conclude by highlighting the need to integrate studies on the biological, sociological, and political aspects of sleep. Our examination of the literature strongly suggests that careful assessment of epidemiological and clinical sleep data should consider the cultural aspects of sleep as well as the context in which sleep occurs, the role of the family, and positive aspects of sleep.

Predictors of Adherence to Nicotine Replacement Therapy (Nicotine Patch) Among Homeless Persons Enrolled in a Randomized Controlled Trial Targeting Smoking Cessation.

INTRODUCTION: Adherence to smoking cessation treatment is generally low, especially among socio-economically disadvantaged groups including individuals experiencing homelessness and those with mental illnesses. Despite the high smoking rates in homeless populations (~70%) no study to date has systematically examined predictors of adherence to nicotine replacement therapy (NRT) in this population. OBJECTIVE: The aim of this secondary analysis was to identify predictors of adherence to NRT in a smoking cessation trial conducted among homeless smokers. METHODS: Secondary analysis of data from a randomized controlled trial enrolling 430 persons who were homeless and current cigarette smokers. Participants were assigned to one of the two study conditions to enhance smoking cessation: Motivational Interviewing (MI; 6 sessions of MI + 8 weeks of NRT) or Standard Care (Brief advice to quit+ 8 weeks of NRT). The primary outcome for the current analysis was adherence to NRT at end of treatment (8 weeks following randomization). Adherence was defined as a total score of zero on a modified Morisky adherence scale). Demographic and baseline psychosocial, tobacco-related, and substance abuse measures were compared between those who did and did not adhere to NRT. RESULTS: After adjusting for confounders, smokers who were depressed at baseline (OR=0.58, 95% CI, 0.38-0.87, p=0.01), had lower confidence to quit (OR=1.10, 95% CI, 1.01-1.19, p=0.04), were less motivated to adhere (OR=1.04, 95% CI, 1.00-1.07, p=0.04), and were less likely to be adherent to NRT. Further, age of initial smoking was positively associated with adherence status (OR= 0.83, 95% CI, 0.69-0.99, p=0.04). CONCLUSION: These results suggest that smoking cessation programs conducted in this population may target increased adherence to NRT by addressing both depression and motivation to quit. TRIAL REGISTRATION: clinicaltrials.gov: NCT00786149.

Binge drinking and insomnia in students from health sciences at one university in Rio de Janeiro, Brazil

In spite of the many studies examining alcohol consumption, recent reviews have indicated that binge drinking has not been extensively studied. Furthermore, it is becoming increasingly clear that sleep is associated with many physiological functions and to drug addictions. The present study aimed to evaluate the relationship between alcohol binge drinking and insomnia in college students of health sciences. All first-year health sciences students (n=286) were evaluated in a cross-sectional study. Envelopes containing the Insomnia Severity Index (ISI), the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and questions capturing sociodemographic data were distributed and collected in classes. It was found that most non-drinkers were female (70.6%), although there were no sex-related differences in the number of binge drinkers (more than 5 drinks on each occasion at least once a week), allowing statistical comparison. The Mann-Whitney U test indicated that the ISI scores were significantly greater in female than male binge drinkers (P=0.014). Moderate or severe insomnia was reported by 23% of the sample, with alcohol being the most frequently associated substance. A specialized intervention was suggested by ASSIST: brief for marijuana (19.2%) and tobacco (23.3%) use, and moderate (31.5%) or intensive (1.4%) for alcohol consumers. The data highlighted the need to pay attention to the habits of college students beyond obtaining scientific information. New data suggesting the influence of genetics on insomnia may be of importance when performing additional studies on the sex differences in alcohol binge drinking.

Sleep-disordered breathing and hypertension among African Americans.

This study investigated differences in sleep-disordered breathing (SDB) between hypertensives without a family history of hypertension and hypertensives with a family history. Furthermore, it examined whether these two groups differed in the severity of SDB. Patients were African Americans (n=162, mean age=51.19+/-13.77 years; mean body mass index (BMI)=37.85+/-9.51 kg/m2, male=57%), who were referred to the clinic because of a sleep complaint. Sleep was recorded in the laboratory using standard physiological parameters; all parameters were analysed by a trained scorer. Altogether, 91% of the patients received an SDB diagnosis. Of these patients, 25% were hypertensives without a family history, 20% were hypertensives with a family history, and 55% were normotensives. We found a significant difference between these patient groups regarding the severity of SDB (F14,158=1.823, P<0.05), but no significant group difference was observed in the rate of SDB. Increasing weight was accompanied by increasing severity of SDB. The finding that hypertensive patients with or without a positive family history showed worse oxygenation and respiratory characteristics than did normotensives is consistent with previous research. Of note, hypertensives reporting a family history were characterized by a greater number of oxygen desaturations and apnoea hypopnoea index than those typified only by a current diagnosis of hypertension. Hypertensives with a family history are likely to show a profile of greater blood pressure, higher BMI, and more severe SDB, which by all accounts are more common among African Americans.

Associations of ambient illumination with mood: contribution of ophthalmic dysfunctions.

Evidence suggests that ocular pathology could reduce light-stimulated neuronal signaling to the suprachiasmatic nuclei. This study investigated associations of ambient illumination with moods, while considering the contribution of ophthalmic dysfunctions. Seventy Black (59%) and White (41%) Americans participated in the study. Their average age was 68.27+/-5.97 years; 73% were women. Baseline data included: physical health, mood, and sociodemographics. Ophthalmic factors including visual acuity, visual field defects, intraocular pressure, vertical and horizontal cup-to-disk ratios, and nerve-fiber-layer thickness were assessed at SUNY Downstate's eye clinic. The following week, participants wore the Actiwatch-L at home to monitor ambient illumination and sleep. Cosine analyses were performed on the logarithm of measured illumination, yielding the mesor and acrophase of daily illumination exposure. Sleep was estimated with an automatic scoring algorithm. Of the sample, 25% reported visual impairment and 85% reported good to excellent health; 27% were visually impaired according to American criteria. Partial correlation analyses showed an inverse correlation of daily illumination levels to depressed mood [r(p)=-0.33, P<0.05], when age, sex, ethnicity, income, BMI, diabetes, hypertension, respiratory disease, and habitual sleep duration were controlled. With further control for ophthalmic factors, the magnitude and significance of the correlation diminished [r(p)=-0.26, NS]. Individuals receiving daily illumination later in the day reported more depressed moods [r(p)=0.36, P<0.01]; of note, this correlation was not significant after control for the covariates [r(p)=0.18, NS]. Regression analysis indicated that the ophthalmic factors explained 13% of the variance in depression. Our results show that both the level and timing of ambient illumination are associated with mood. Furthermore, they suggest that visual impairment has a mediating effect on the associations of ambient illumination with depression, supporting the notion that ocular pathology lessens the efficacy of daily illumination in promoting positive moods.

No melatonin suppression by illumination of popliteal fossae or eyelids.

A recent report that popliteal illumination shifted the circadian rhythms of body temperature and melatonin challenged the longstanding belief that light phase-shifting the circadian system in mammals is mediated only through the retina. The authors tested effects of popliteal illumination and illumination provided through the eyelids on melatonin suppression. In randomized, counterbalanced orders, healthy volunteers received three treatments from midnight until 2:00 AM, one on each of three visits to the laboratory. Treatments included (1) no illumination from light pads applied to the popliteal fossae, with light mask maintained at < 3 lux (control); (2) light mask illuminated at 1700 lux, with popliteal light pads extinguished; and (3) popliteal light pads illuminated (13,000 lux) and light mask at < 3 lux (control). Saliva specimens were sampled at midnight, at 1:00 AM, and at 2:00 AM. Mean salivary melatonin concentrations rose from an average of 30.8 (3.9) pg/ml at midnight (baseline), to 33.2 (4.0) pg/ml at 1:00 AM, and to 37.2 (3.8) pg/ml at 2:00 AM in all three conditions, but no statistical differences were found using repeated-measures ANOVA. No evidence of melatonin suppression by either popliteal or closed eyelid light stimulation was found. These data suggest that bright retinal illumination is necessary for suppression of melatonin mediated through the suprachiasmatic nuclei.

Predictors of Obstructive Sleep Apnea Risk among Blacks with Metabolic Syndrome.

INTRODUCTION: Identification of risk factors for obstructive sleep apnea (OSA) is important to enable comprehensive intervention to reduce OSA-related cardiovascular disease (CVD). The metabolic syndrome outcome study (MetSO) provides a unique opportunity to address these factors. This study investigated risk of OSA among blacks with metabolic syndrome. METHODS: The present study utilized data from MetSO, an NIH-funded cohort study of blacks with metabolic syndrome. A total of 1,035 patients provided data for the analysis. These included sociodemographic factors, health risks, and medical history. Physician-diagnosed conditions were obtained using an electronic medical record system (Allscripts, Sunrise Enterprise). Patients were diagnosed with metabolic syndrome using criteria articulated in the joint interim statement for harmonizing the metabolic syndrome. Patients with a score ≥6 on the Apnea Risk Evaluation System (ARES) questionnaire were considered at risk for OSA. Obesity is defined by body mass index (BMI ≥ 30 kg/m2). RESULTS: Of the 1,035 patients screened in the MetSO cohort, 48.9% were at high risk for OSA. Using multivariate-adjusted logistic regression analysis, we observed that obesity was the strongest predictor of OSA risk (OR=1.59, 95%CI=1.24-2.04, p<0.0001). This finding remained significant even after adjustment for known covariates including blood pressure, low-density lipoprotein, high-density lipoprotein, and glucose levels (OR=1.44, 95%CI=1.11-1.86, p<0.001). CONCLUSION: Blacks in the MetSO cohort are at greater OSA risk, relative to the adult population in developed countries. Consistent with previous observations, obesity proved the strongest independent predictor of OSA risk among blacks with metabolic syndrome.

METABOLIC EFFECTS OF MARIJUANA USE AMONG BLACKS.

BACKGROUND: Increased legalization of marijuana has resulted in renewed interest in its effects on body weight and cardiometabolic risk. Conflicting data exist regarding marijuana effects on body weight, waist circumference as well as lipid profiles, blood pressure and cardiovascular disease. Furthermore, there is a dearth of data available on this effect in the black population. OBJECTIVE: To assess the metabolic profile and cardiovascular risk factors as well as body weight and waist circumference among urban black marijuana users. METHODS: A cross sectional study design involving 100 patients seen in a Family Practice clinic at University hospital of Brooklyn, NY, USA, over a period of 3 months from January 2014 to March 2014. Participants were administered a questionnaire regarding marijuana use, and other associated behaviors. Socio-demographic, laboratory, and clinical data were collected. We report measures of central tendencies, and dispersion for continuous variables and the frequency of distribution for categorical variables. RESULTS: Of the 100 patients surveyed, 57% were females. The mean (±SEM) age of the entire cohort was 46.3 years±1.5; range, 19-78 years. The mean body mass index (BMI) was 29.6 kg/m2±0.73; SBP=128.0 mmHg±1.69; DBP=76.1 mmHg±1.17. Current marijuana users had the lowest waist circumference compared to former or never users respectively (32.9±0.66 vs. 35.9±0.88 vs. 33.4±0.74), p<0.01. Diastolic blood pressure in mmHg was significantly higher among former marijuana users compared to current or never users, (80.0±2.1 vs. 73.3±2.3 vs. 73.4±1.6), p<0.01. Current marijuana users showed a tendency (not statistically significant) towards lower total cholesterol, Triglycerides (TG), High Density Lipoprotein (HDL)-cholesterol, Low Density Lipoprotein (LDL)-cholesterol, body mass index (BMI) and systolic blood pressure, compared to former users or never users. CONCLUSION: Current marijuana use is associated with significantly lower waist circumference, compared to former users and never users. Except for diastolic BP that was significantly lower among current users, other metabolic parameters showed tendency towards favorable profile. Further studies are needed to characterize the metabolic effects and to elucidate mechanisms of actions of marijuana in view of its rapid rate of utilization in the USA and around the world.

Sleep duration, illumination, and activity patterns in a population sample: effects of gender and ethnicity.

BACKGROUND: Current knowledge of the population's sleep durations emanates primarily from questionnaires and laboratory studies. Using Actillumes, we investigated whether self-reported sleep durations were indicative of a population decline in sleep duration. We also explored illumination and activity patterns. METHODS: San Diego adults (n = 273, age range: 40-64) were recruited through random telephone calls and were monitored at home while engaging in usual daily routines. RESULTS: Volunteers slept an average of 6.22 hours and received an average of 554 lux (environmental illumination). The timing of sleep, illumination, and activity occurred at 2:44, 12:57, and 13:43, respectively. Irrespective of ethnicity, age, and time reference, men received greater illumination than did women, but this gender effect was not independent of work status. Women and men exhibited a similar circadian activity profile; however, women exhibited better sleep-wake patterns. Interactions between gender and ethnicity suggested worse sleep-wake patterns among minority men. An age-related decline in activity was found, but no age trend in sleep duration or illumination patterns was observed. CONCLUSIONS: This study showed an objective population decline in sleep duration. Sociodemographic effects should be considered in analyses of sleep-wake patterns and illumination exposures.

Sleep and quality of well-being.

BACKGROUND: It is commonly believed that sleep duration in the population has been declining gradually. Whereas sleep restriction in the laboratory induces sleepiness and mood disturbances, it is not certain whether a short sleep duration impairs the quality of everyday life. METHODS: Using population-based data, we explored whether greater habitual sleep duration is a predictor of better health-related quality of life, measured by the Quality of Well-Being (QWB) scale. The relationships between QWB and several potential correlates were examined in a stepwise linear regression analysis. RESULTS: Neither subjective nor actigraphic sleep duration were associated with QWB. Greater quality of well-being was associated with greater sleep satisfaction, younger age, less obesity, non-Hispanic White ethnicity, and greater experienced illumination. CONCLUSION: These data suggest that increasing sleep duration may not directly improve quality of life, despite evidence that curtailment of nocturnal sleep is associated with fatigue.

Determination of sleep and wakefulness with the actigraph data analysis software (ADAS).

Current evidence has shown that, overall, actigraphy is an excellent tool for unobtrusive documentation of sleep/wake activity in normal individuals. However, a number of methodological issues remain to be resolved to warrant its use in clinical research. In this paper, we report the results of a study aimed at the development of a new scoring software that can accurately identify sleep and wakefulness. Using total sleep time as an index of comparison, the software was optimized on a calibration sample and prospectively tested on a validation sample. A strong correlation coefficient (r = 0.93, p < 0.008), with an average discrepancy value of 10 minutes, was observed for the calibration sample. The application of the optimal software to the validation sample revealed an even higher correlation coefficient (r = 0.97, p < 0.0001), with an average discrepancy value of 12 minutes.