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Study Objectives: There is mixed evidence regarding associations of sleep duration with academic functioning in adolescents and a lack of research on other sleep dimensions, particularly using objective sleep measures. We examined associations of multiple actigraphic sleep dimensions with academic functioning among adolescents., Methods: Data were from the sleep sub-study of the age 15 wave of the Future of Families and Child Wellbeing Study (n = 774-782; 52% female), a national, diverse sample of teens. Adolescents wore wrist-actigraphs for ~1 week and completed a survey reporting academic performance and school-related behavioral problems. Regression models assessed whether average sleep duration, timing, maintenance efficiency, and SD-variability were associated with self-reported academic functioning in cross-sectional analyses adjusted for demographic characteristics, depressive symptoms, and anxious symptoms., Results: Later sleep timing (hours) and greater sleep variability (SD-hours) were associated with poorer academic outcomes, including sleep onset variability with higher odds of receiving a D or lower (OR = 1.29), sleep onset (β = -.07), sleep offset (β = -.08), and sleep duration variability (β = -.08) with fewer A grades, sleep offset with lower GPA (β = -.07), sleep offset (OR = 1.11), sleep duration variability (OR = 1.31), and sleep onset variability (OR = 1.42) with higher odds of being suspended or expelled in the past 2 years, and sleep duration variability with greater trouble at school (β = .13). Sleep duration, sleep maintenance efficiency, and sleep regularity index were not associated with academic functioning., Conclusions: Later sleep timing and greater sleep variability are risk factors for certain academic problems among adolescents. Promoting sufficient, regular sleep timing across the week may improve adolescent academic functioning., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Most research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants focuses on initial symptomatology with limited longer-term data. We characterized prevalences of prolonged symptoms 3 months post-SARS-CoV-2 infection across 3 variant time-periods (pre-Delta, Delta, and Omicron)., Methods: This multicenter prospective cohort study of adults with acute illness tested for SARS-CoV-2 compared fatigue severity, fatigue symptoms, organ system-based symptoms, and ≥3 symptoms across variants among participants with a positive ("COVID-positive") or negative SARS-CoV-2 test ("COVID-negative") at 3 months after SARS-CoV-2 testing. Variant periods were defined by dates with ≥50% dominant strain. We performed multivariable logistic regression modeling to estimate independent effects of variants adjusting for sociodemographics, baseline health, and vaccine status., Results: The study included 2402 COVID-positive and 821 COVID-negative participants. Among COVID-positives, 463 (19.3%) were pre-Delta, 1198 (49.9%) Delta, and 741 (30.8%) Omicron. The pre-Delta COVID-positive cohort exhibited more prolonged severe fatigue (16.7% vs 11.5% vs 12.3%; P = .017) and presence of ≥3 prolonged symptoms (28.4% vs 21.7% vs 16.0%; P < .001) compared with the Delta and Omicron cohorts. No differences were seen in the COVID-negatives across time-periods. In multivariable models adjusted for vaccination, severe fatigue and odds of having ≥3 symptoms were no longer significant across variants., Conclusions: Prolonged symptoms following SARS-CoV-2 infection were more common among participants infected during pre-Delta than with Delta and Omicron; however, these differences were no longer significant after adjusting for vaccination status, suggesting a beneficial effect of vaccination on risk of long-term symptoms. Clinical Trials Registration. NCT04610515., Competing Interests: Potential conflicts of interest. M. G. reports the following institutional funding: Rush Center for Emerging Infectious Diseases Research Grant, Society for Academic Emergency Medicine Grant, Emergency Medicine Foundation/Council of Residency Directors in Emergency Medicine Education Research Grant, Emergency Medicine: Reviews and Perspectives Medical Education Research Grant, and University of Ottawa Department of Medicine Education Grant. E. S. S. receives grant funding from the National Institute on Minority Health and Health Disparities (U54MD010711-01), the US Food and Drug Administration (FDA) to support projects within the Yale–Mayo Clinic Center of Excellence in Regulatory Science and Innovation (U01FD005938), the National Institute of Biomedical Imaging and Bioengineering (R01 EB028106-01), and the National Heart, Lung, and Blood Institute (R01HL151240); and has received honorarium paid to author for a 1-day educational session from Regeneron. J. G. E. reports serving as Editor in Chief of Adult Primary Care topics for UpToDate. A. V. reports funding for coronavirus disease 2019 (COVID-19)–related studies from the Society of Academic Emergency Medicine Foundation Emerging Infectious Disease and Preparedness Grant, the Agency for Healthcare Research and Quality (R01 HS 28340-01), the FDA (ID: 75F40120C00174), and the Emergency Medicine Health Policy Institute/Emergency Medicine Foundation; grants or contracts from the American Board of Emergency Medicine National Academy of Medicine Fellowship, Centers for Medicare and Medicaid Services, National Institute on Drug Abuse, Moore Foundation, Genentech, and FORE Foundation; consulting fees from Liminal Sciences; payment for expert testimony from Salvi, Shostok & Pritchard; support for attending meetings and/or travel from the American College of Emergency Physician, and stock or stock options with Hyperfine Inc/Liminal Sciences. A. H. I. reports participation on a data and safety monitoring board (DSMB) or advisory board for Stryker, Inc. A. M. C. reports grants or contracts from the CDC, unrelated to this work. L. E. W. reports participation on a DSMB or advisory board for a diabetes project at University of Washington. R. R. reports a grant from the National Institute of Allergy and Infectious Diseases (R01 AI166967-01, all payments made to the University of California, San Francisco). R. A. W. reports consulting fees from UpToDate as a reviewer for infection control sections, and participation as unpaid member of a scientific advisory board for the European Clinical Research Alliance on Infectious Diseases Foundation. S. M. reports an NIH Institutional Training Grant (5KL2TR003981-02), not related to the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Long-term symptoms following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are a major concern, yet their prevalence is poorly understood., Methods: We conducted a prospective cohort study comparing adults with SARS-CoV-2 infection (coronavirus disease-positive [COVID+]) with adults who tested negative (COVID-), enrolled within 28 days of a Food and Drug Administration (FDA)-approved SARS-CoV-2 test result for active symptoms. Sociodemographic characteristics, symptoms of SARS-CoV-2 infection (assessed with the Centers for Disease Control and Prevention [CDC] Person Under Investigation Symptom List), and symptoms of post-infectious syndromes (ie, fatigue, sleep quality, muscle/joint pains, unrefreshing sleep, and dizziness/fainting, assessed with CDC Short Symptom Screener for myalgic encephalomyelitis/chronic fatigue syndrome) were assessed at baseline and 3 months via electronic surveys sent via text or email., Results: Among the first 1000 participants, 722 were COVID+ and 278 were COVID-. Mean age was 41.5 (SD 15.2); 66.3% were female, 13.4% were Black, and 15.3% were Hispanic. At baseline, SARS-CoV-2 symptoms were more common in the COVID+ group than the COVID- group. At 3 months, SARS-CoV-2 symptoms declined in both groups, although were more prevalent in the COVID+ group: upper respiratory symptoms/head/eyes/ears/nose/throat (HEENT; 37.3% vs 20.9%), constitutional (28.8% vs 19.4%), musculoskeletal (19.5% vs 14.7%), pulmonary (17.6% vs 12.2%), cardiovascular (10.0% vs 7.2%), and gastrointestinal (8.7% vs 8.3%); only 50.2% and 73.3% reported no symptoms at all. Symptoms of post-infectious syndromes were similarly prevalent among the COVID+ and COVID- groups at 3 months., Conclusions: Approximately half of COVID+ participants, as compared with one-quarter of COVID- participants, had at least 1 SARS-CoV-2 symptom at 3 months, highlighting the need for future work to distinguish long COVID., Clinical Trials Registration: NCT04610515., Competing Interests: Potential conflicts of interest . All authors: No potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Job discrimination, a social stressor, may lead to sleep health disparities among workers; yet, limited research has examined this relationship and specific sources of job discrimination. We used a US sample of working women (n = 26,085), participants in the Sister Study (2008-2016), to examine the associations of perceived job discrimination due to sex, race, age, health conditions, and/or sexual orientation with sleep health. Cross-sectionally, linear or logistic regression models revealed that each source of job discrimination was independently associated with different sleep problems after controlling for other sources of job discrimination. Longitudinally, among participants without short sleep (<7 hours/night) at time 1 (2012-2014), age-specific job discrimination was associated with 21% increased odds of new-onset short sleep (odds ratio = 1.21, 95% confidence interval: 1.03, 1.43) at time 2 (2014-2016). Among those without insomnia symptoms at time 1, race-specific job discrimination was associated with 37% increased odds of new-onset insomnia symptoms (odds ratio = 1.37, 95% confidence interval: 1.07, 1.75) at time 2. Sex- and health-specific job discrimination also predicted new-onset sleepiness. There were dose-response relationships such that a greater number of sources of job discrimination (≥3) was associated with greater odds of prevalent and incident sleep problems. Perceived job discrimination may contribute to working women's poor sleep health over time, raising concerns about sleep health disparities emanating from the workplace., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Highly pathogenic avian influenza (HPAI) A(H5) viruses belonging to clade 2.3.4.4c of the A/goose/Guangdong/1/96-like (Gs/GD) lineage caused severe global outbreaks in domestic birds from 2014 to 2015, that also represented the first incursions of Gs/GD viruses into Taiwan and the USA. However, few studies have investigated the circulation of clade 2.3.4.4c viruses after 2015. Here, we describe Gs/GD clade 2.3.4.4c and Mexican-like H5N2 viruses that were isolated in Taiwan during active surveillance conducted in chicken farms from February to March 2019. Phylogenetic analysis demonstrated two distinct genome constellations of the clade 2.3.4.4c H5 viruses, with the internal genes of one of the new genotypes closely related to a virus isolated from a pintail ( Anas acuta ) in Taiwan, providing the first direct evidence that migratory birds play a role in importing viruses into Taiwan. Our study also confirmed the co-circulation of Gs/GD clade 2.3.4.4c and Mexican-like H5 lineage viruses in Taiwan, presenting a rare case where Gs/GD viruses developed sustained transmission alongside another enzootic H5 lineage, raising the possibility that homosubtypic immunity may mask virus transmission, potentially frustrating detection, and the implementation of appropriate control measures. To eradicate H5 viruses from poultry in Taiwan, further studies on the effect of co-circulation in poultry of low pathogenic avian influenza and HPAI viruses are needed. Furthermore, only with continued surveillance efforts globally can we fully discern dispersal patterns and risk factors of virus transmission both to and within Taiwan., (© The Author(s) 2020. Published by Oxford University Press.)

Study Objectives: High school start times (SSTs) directly impact adolescents' sleep timing and duration. This study investigated the associations between SSTs and actigraphically-measured 24-hour sleep duration, sleep onset, sleep offset and sleep quality., Methods: This study included 383 adolescents (Mage = 15.5, SDage = 0.6 years) participating in the age 15 wave of the Fragile Families & Child Wellbeing Study, a national birth cohort study sampling from 20 large US cities. Multilevel models used daily observations (N = 1116 school days, Mdays = 2.9, SDdays = 1.4 per adolescent) of sleep and SSTs from concordant daily diary and actigraphy., Results: A diverse range of SSTs were included in our analyses (MSST = 08:08, SDSST = 39 minutes, RangeSST = 06:00-11:05), and are presented in the following categories for ease of interpretation: before 07:30, 07:30-07:59, 08:00-08:29, and 08:30 or later. Adolescents starting school at 08:30 or later exhibited significantly longer actigraphically-assessed 24-hour sleep duration (by 21-34 minutes, p < .05) and later sleep offset (by 32-64 minutes, p < .001) when compared with the adolescents grouped by earlier SSTs. SSTs were also analyzed continuously for comparison with existing literature, and results indicated that every 1-hour delay in SST was significantly associated with 21 minutes longer 24-hour sleep duration (p < .001), 16 minutes later sleep onset (p < .01), and 39 minutes later sleep offset (p < .001). All models controlled for covariates including socioeconomic status., Conclusion: These findings support pediatric and public health expert recommendations for SSTs after 08:30. In our diverse national urban sample, adolescents with SSTs at 08:30 or later, compared with adolescents with earlier SSTs, had significantly longer actigraphy-measured sleep.

Study Objectives: Short and long sleep durations are linked to reduced kidney function, but little research has examined how sleep is associated with hydration status. Our aim was to assess the relationship between sleep duration and urinary hydration biomarkers among adults in a cross-cultural context., Methods: Three samples of adults aged ≥20 years were analyzed: 2007-2008 National Health and Nutrition Examination Survey (NHANES; n = 4680), 2009-2012 NHANES (n = 9559), and 2012 cross-sectional wave of the Chinese Kailuan Study (n = 11903), excluding pregnant women and adults with failing kidneys. We estimated multiple linear regression models between self-reported usual night-time sleep duration (<6, 6, 7, 8 (reference), and ≥9 hr/day) and urine specific gravity (Usg) and urine osmolality (Uosm) as continuous variables and logistic regression models dichotomized as inadequate hydration (>1.020 g/mL; >831 mOsm/kg). In primary analyses, we estimated models excluding diabetes and diuretic medications for healthier subpopulations (NHANES, n = 11353; Kailuan, n = 8766)., Results: In the healthier NHANES subset, 6 hr was associated with significantly higher Usg and odds of inadequate hydration (adjusted OR: 1.59, 95% CI: 1.25, 2.03) compared with 8 hr. Regression results were mixed using Uosm, but in the same direction as Usg. Among Chinese adults, short sleep duration (<6 and 6 hr) was associated with Usg and higher likelihood of inadequate hydration (6 hr adjusted OR: 1.42, 95% CI: 1.26, 1.60). No consistent association was found with sleeping ≥9 hr., Conclusions: Short sleep duration was associated with higher odds of inadequate hydration in US and Chinese adults relative to sleeping 8 hr.

Study Objectives: Having a regular, age-appropriate bedtime and sufficient sleep from early childhood may be important for healthy weight in adolescence. This study aimed to (1) identify heterogeneous groups of children by bedtime and sleep routines and (2) test longitudinal associations of childhood bedtime and sleep routine groups with adolescent body mass index (BMI)., Methods: We analyzed longitudinal data from the Fragile Families and Child Wellbeing Study, a national birth cohort from 20 US cities (N = 2196). Childhood bedtime and sleep routines were assessed by mothers' reports of their children's presence and timing of bedtimes, adherence to bedtimes, and habitual sleep duration at ages 5 and 9. At age 15, these adolescents reported their height and weight, which were used to calculate BMI z-score., Results: Latent Class Analysis revealed four groups of childhood bedtime and sleep routines: No Bedtime Routine Age 5 (Group 1), No Bedtime Routine Age 9 (Group 2), Borderline Bedtimes Ages 5 and 9 (Group 3), and Age-Appropriate Bedtime and Sleep Routines Ages 5 and 9 (Group 4, reference). Compared with adolescents in the reference group, those in the No Bedtime Routine Age 9 (Group 2) had +0.38 SD greater BMI (95% CI = [0.13 to 0.63]), above the level for overweight (1.02 SD BMI/85th percentile). Associations persisted after adjusting for age 3 BMI and sociodemographic characteristics., Conclusions: Results demonstrate heterogeneity in childhood bedtime routine groups and their associations with adolescent BMI. Future studies should focus on whether childhood sleep behavior interventions promote healthier sleep and weight in later life course stages.

Study Objectives: Light can induce an acute alerting response in humans; however, it is unknown whether the magnitude of this response is simply a function of the absolute illuminance of the light itself, or whether it depends on illuminance history preceding the stimulus. Here, we compared the effects of illuminance history on the alerting response to a subsequent light stimulus., Design: A randomized, crossover design was used to compare the effect of two illuminance histories (1 lux vs. 90 lux) on the alerting response to a 6.5-h 90-lux light stimulus during the biological night., Setting: Intensive Physiologic Monitoring Unit, Brigham and Women's Hospital, Boston, MA., Participants: Fourteen healthy young adults (6 F; 23.5 ± 2.9 years)., Interventions: Participants were administered two 6.5-h light exposures (LE) of 90 lux during the biological night. For 3 days prior to each LE, participants were exposed to either 1 lux or 90 lux during the wake episode., Measurements and Results: The alerting response to light was assessed using subjective sleepiness ratings, lapses of attention, and reaction times as measured with an auditory psychomotor vigilance task, as well as power density in the delta/theta range of the waking EEG. The alerting response to light was greater and lasted longer when the LE followed exposure to 1 lux compared to 90 lux light., Conclusion: The magnitude and duration of the alerting effect of light at night depends on the illuminance history and appears to be subject to sensitization and adaptation.

Background: The biological role(s) of glomerular parietal epithelial cells (PECs) is not fully understood in health or disease. Given its location, PECs are constantly exposed to low levels of filtered albumin, which is increased in nephrotic states. We tested the hypothesis that PECs internalize albumin and increased uptake results in apoptosis., Methods: Confocal microscopy of immunofluorescent staining and immunohistochemistry were used to demonstrate albumin internalization in PECs and to quantitate albumin uptake in normal mice and rats as well as experimental models of membranous nephropathy, minimal change disease/focal segmental glomerulosclerosis and protein overload nephropathy. Fluorescence-activated cell sorting analysis was performed on immortalized cultured PECs exposed to fluorescein isothiocyanate (FITC)-labeled albumin in the presence of an endosomal inhibitor or vehicle. Apoptosis was measured by Hoechst staining in cultured PECs exposed to bovine serum albumin. Levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) were restored by retroviral infection of mitogen-activated protein kinase (MEK) 1/2 and reduced by U0126 in PECs exposed to high albumin levels in culture and apoptosis measured by Hoechst staining., Results: PECs internalized albumin normally, and this was markedly increased in all of the experimental disease models (P<0.05 versus controls). Cultured immortalized PECs also internalize FITC-labeled albumin, which was reduced by endosomal inhibition. A consequence of increased albumin internalization was PEC apoptosis in vitro and in vivo. Candidate signaling pathways underlying these events were examined. Data showed markedly reduced levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) in PECs exposed to high albumin levels in nephropathy and in culture. A role for ERK1/2 in limiting albumin-induced apoptosis was shown by restoring p-ERK1/2 by retroviral infection, which reduced apoptosis in cultured PECs, while a forced decrease of p-ERK1/2 through inhibition of MEK 1/2 significantly increased albumin-induced PEC apoptosis., Conclusions: A normal role of PECs is to take up filtered albumin. However, this is increased in proteinuric glomerular diseases, leading to apoptosis through changes in ERK1/2.

Objectives: Performance on many cognitive tasks varies with time awake and with circadian phase, and the forced desynchrony (FD) protocol can be used to separate these influences on performance. Some performance tasks show practice effects, whereas the Psychomotor Vigilance Task (PVT) has been reported not to show such effects. We aimed to compare performance on the PVT and on an addition test (ADD) across a 6-week FD study, to determine whether practice effects were present and to analyze the circadian and wake-dependent modulation of the 2 measures., Design and Setting: A 47-day FD study conducted at the Brigham and Women's Hospital General Clinical Research Center., Participants: Eleven healthy adults (mean age: 24.4 years, 2 women)., Measurements and Results: For 2 baseline days and across 6 weeks of FD, we gave a test battery (ADD, PVT, self-rating of effort and performance) every 2 hours. During FD, there was a significant (P < 0.0001) improvement in ADD performance (more correct calculations completed), whereas PVT performance (mean reaction time, fastest 10% reaction times, lapses) significantly (P < 0.0001) declined week by week. Subjective ratings of PVT performance indicated that subjects felt their performance improved across the study (P < 0.0001), but their rating of whether they could have performed better with greater effort did not change across the study (P > 0.05)., Conclusions: The decline in PVT performance suggests a cumulative effect of sleep loss across the 6-week study. Subjects did not accurately detect their declining PVT performance, and a motivational factor could not explain this decline.

Background: There is a high prevalence of diabetes and impaired glucose tolerance (IGT) in the older population. Normal aging is associated with insulin resistance and impaired insulin secretion, with greater defects in people with IGT. Short-term exercise has been found to increase insulin sensitivity, but little is known about acute exercise effects on beta-cell function in older people with IGT., Methods: We assessed the effects of 7 consecutive days of supervised aerobic exercise (1 h/d at 60-70% heart rate reserve) in 12 sedentary older people with IGT. Screening included oral glucose tolerance test, stress/maximal O(2) uptake test, and dual-energy x-ray absorptiometry scan. Participants had a frequently sampled iv glucose tolerance test at baseline and 15-20 h after the seventh exercise session. Insulin sensitivity (S(I)), glucose disappearance constant (Kg, a measure of iv glucose tolerance), acute insulin response to glucose (AIRg), and disposition index (AIRg x S(I)), a measure of beta-cell function in relation to insulin resistance, were calculated., Results: Exercise was well tolerated. Body weight, fasting glucose, fasting insulin, and iv glucose tolerance were unchanged with exercise. S(I) increased by 59%, AIRg decreased by 12%, and disposition index increased by 31%. There was no significant change in fasting lipid, catecholamine, leptin, or adiponectin levels., Conclusions: Short-term exercise not only improved insulin resistance but also significantly enhanced beta-cell function in older people with IGT. These effects of short-term exercise on beta-cell function cannot be explained by changes in body weight or circulating levels of lipids, leptin, adiponectin, or catecholamines.

Context: Glucose tolerance declines with age and may involve impaired beta-cell sensitivity to glucose and beta-cell compensation for insulin resistance., Objective: We investigated beta-cell sensitivity to glucose and beta-cell compensation for nicotinic acid-induced insulin resistance in young (age <35 yr) people with normal glucose tolerance (NGT) and old (age >60 yr) people with NGT and impaired glucose tolerance (IGT). DESIGN/PATIENTS/SETTING/INTERVENTION: Fifteen young NGT, 16 old NGT, and 14 old IGT were randomized to 2-wk treatment with nicotinic acid or placebo in a double-blind, crossover study in a university medical setting. At the end of each treatment period, participants had a frequently sampled iv glucose tolerance test and ramp clamp, in which insulin secretion rates (ISR) were determined in response to a matched 5-10 mm glucose stimulus., Main Outcome Measures: Insulin sensitivity (S(I)), acute insulin response to iv glucose (AIRg), and disposition index (AIRg x S(I), or beta-cell compensation for insulin resistance) from frequently sampled iv glucose tolerance testing, and ISR area under the curve (or beta-cell sensitivity to glucose) from ramp clamp were determined., Results: Progressive impairments in insulin secretion as assessed by AIRg, disposition index, and ISR area under the curve were identified in older people with NGT, with more marked defects in older people with IGT. Nicotinic acid treatment significantly reduced S(I) in all groups. beta-Cell compensation for nicotinic acid-induced insulin resistance was incomplete in all three groups, with greater defects in the two older groups., Conclusions: Human aging is associated with impaired beta-cell sensitivity to glucose and impaired beta-cell compensation to insulin resistance.

Context: Studies in older people have shown inconsistent agreement between homeostasis model assessment of insulin resistance (HOMA-IR) and dynamic measures of insulin action and have not evaluated HOMA beta-cell., Objective: We compared measures of insulin sensitivity and beta-cell function from the frequently sampled iv glucose tolerance test (FSIGT) to HOMA models. DESIGN/PATIENTS/SETTING/INTERVENTION: Two hundred fourteen young and old with normal glucose tolerance (NGT) and old with impaired glucose tolerance (IGT) participated in a retrospective analysis of FSIGT data in a university medical setting., Main Outcome Measure: Sensitivity to insulin (S(I)) and acute insulin response to glucose (AIRg) from FSIGT were compared with HOMA models., Results: S(I) and HOMA-IR measures identified similar patterns of increasing insulin resistance in the two older groups, compared with younger people with NGT, with the greatest degree of insulin resistance in older people with IGT (P < 0.05 vs. young and old NGT for both S(I) and HOMA-IR). Agreement between HOMA-IR and S(I) was moderate (weighted kappa = 0.51). AIRg was similar in young and old NGT but was markedly decreased in old IGT (P < 0.05 vs. young and old NGT). HOMA-beta-cell was similar in the three groups. Agreement between HOMA beta-cell and AIRg was weak (weighted kappa = 0.35)., Conclusions: HOMA-IR may detect age-related insulin resistance when comparing large populations of older people. However, dynamic testing appears to be necessary to quantitate diminished insulin secretion in older people.

Background: Recently, much interest has been generated on the fetomaternal transfer of nucleated cells and plasma DNA. However, there has been no systematic quantitative comparison of these two directions and two modalities of trafficking within the same study population., Methods: The fetus-to-mother transfer of nucleated cells and plasma DNA in pregnant women carrying male babies was studied using a real-time quantitative PCR assay for the S:RY gene. For mother-to-fetus transfer, real-time quantitative PCR assays for the insertion/deletion polymorphisms involving the glutathione S:-transferase M1 and angiotensin-converting enzyme genes were used., Results: Of the 50 informative mother-baby pairs, maternal DNA was detected in the cellular fraction of umbilical cord blood in 24% of cases (12 of 50), at a median fractional concentration of 2.6 x 10(-4) (interquartile range, 1.7 x 10(-4) to 3.6 x 10(-4)). In the plasma fraction of cord blood, maternal DNA was detected in 30% (15 of 50) of cases at a median fractional concentration of 3 x 10(-3) (interquartile range, 1 x 10(-3) to 1.6 x 10(-2)). For the other direction of trafficking, fetus-to-mother transfer of nucleated cells was detected in 26% of cases (13 of 50) at a median fractional concentration of 3.2 x 10(-4) (interquartile range, 0.6 x 10(-4) to 7.6 x 10(-4)). In the plasma fraction, fetal DNA was detected in 100% of maternal plasma (50 of 50) at a median fractional concentration of 3 x 10(-2) (interquartile range, 1.4 x 10(-2) to 5. 3 x 10(-2))., Conclusions: This study indicated that significantly more fetal DNA is present in the plasma of pregnant women compared with DNA from the cellular fraction of maternal blood. In addition, maternal DNA was demonstrated in both the cellular and plasma fractions of cord blood after delivery. This study has therefore determined the fundamental quantitative values for the bidirectional fetomaternal cellular and plasma DNA traffic.

An education program was developed and evaluated to determine its efficacy in increasing knowledge and decreasing the severity of symptoms of premenstrual syndrome (PMS). Participants from a sample of 94 schoolgirls aged between 14 and 18 years from four secondary schools in Hong Kong were assigned to either the experimental or control group. Immediately following the education program, the schoolgirls in the experimental group had significantly increased knowledge scores as measured by the Premenstrual Syndrome Knowledge Questionnaire. Three months following the education program, schoolgirls in the experimental group reported having a significant reduction in total PMS scores and three of the subscale scores as measured by a translated version of Abraham's Menstrual Symptom Questionnaire. In addition, no significant differences were found for the control group on pre-test and post-test PMS scores suggesting that the education program could have been the source of the reduction in PMS symptoms of the experimental group of young adolescents girls.

Background: The recent discovery of the presence of circulating cell-free fetal DNA in maternal plasma opens up new prenatal diagnostic applications and provides new avenues for clinical investigation. It is of research and potential diagnostic interest to determine whether fetal trisomy 21 may be associated with quantitative abnormalities of circulating fetal DNA in maternal plasma., Methods: Maternal plasma samples were prospectively collected from two centers situated in Hong Kong and Boston. Samples collected from Boston consisted of 7 women carrying male trisomy 21 fetuses, 19 carrying euploid male fetuses, and 13 carrying female fetuses. Samples collected from Hong Kong consisted of 6 women carrying male trisomy 21 fetuses, 18 carrying euploid male fetuses, and 10 carrying female fetuses. Male fetal DNA in maternal plasma was measured using real-time quantitative Y-chromosomal PCR., Results: For patients recruited from Boston, the median circulating fetal DNA concentrations in women carrying trisomy 21 and euploid male fetuses were 46.0 genome-equivalents/mL and 23.3 genome-equivalents/mL, respectively (P = 0.028). For patients recruited from Hong Kong, the median circulating fetal DNA concentrations in women carrying trisomy 21 and euploid male fetuses were 48.2 genome-equivalents/mL and 16.3 genome-equivalents/mL, respectively (P = 0.026). None of the samples from women carrying female fetuses had detectable Y-chromosomal signals., Conclusions: Abnormally high concentrations of circulating fetal DNA are found in a proportion of women carrying fetuses with trisomy 21. The robustness and reproducibility of real-time PCR analysis of maternal plasma makes it a valuable tool for cross-institutional collaboration involving centers located in different parts of the world.

Clock is a semidominant mutation identified from an N-ethyl-N-nitrosourea mutagenesis screen in mice. Mice carrying the Clock mutation exhibit abnormalities of circadian behavior, including lengthening of endogenous period and loss of rhythmicity. To identify the gene affected by this mutation, we have generated a high-resolution genetic map (> 1800 meioses) of the Clock locus. We report that Clock is 0.7 cM distal of Kit on mouse chromosome 5. Mapping shows that Clock lies within the W19H deletion. Complementation analysis of different Clock and W19H compound genotypes indicates that the Clock mutation behaves as an antimorph. This antimorphic behavior of Clock strongly argues that Clock defines a gene centrally involved in the mammalian circadian system.