Insomnia with Short Sleep Duration and Mortality: The Penn State Cohort

Study Objectives:

Because insomnia with objective short sleep duration is associated with increased morbidity, we examined the effects of this insomnia subtype on all-cause mortality.

Design:

Longitudinal.

Setting:

Sleep laboratory.

Participants:

1,741 men and women randomly selected from Central Pennsylvania.

Measurements:

Participants were studied in the sleep laboratory and were followed-up for 14 years (men) and 10 years (women). “Insomnia” was defined by a complaint of insomnia with duration ≥ 1 year. “Normal sleeping” was defined as absence of insomnia. Polysomnographic sleep duration was classified into two categories: the “normal sleep duration group” subjects who slept ≥ 6 h and the “short sleep duration group” subjects who slept < 6 h. We adjusted for age, race, education, body mass index, smoking, alcohol, depression, sleep disordered breathing, and sampling weight.

Results:

The mortality rate was 21% for men and 5% for women. In men, mortality risk was significantly increased in insomniacs who slept less than 6 hours compared to the “normal sleep duration, no insomnia” group, (OR = 4.00, CI 1.14-13.99) after adjusting for diabetes, hypertension, and other confounders. Furthermore, there was a marginally significant trend (P = 0.15) towards higher mortality risk from insomnia and short sleep in patients with diabetes or hypertension (OR = 7.17, 95% CI 1.41-36.62) than in those without these comorbid conditions (OR = 1.45, 95% CI 0.13-16.14). In women, mortality was not associated with insomnia and short sleep duration.

Conclusions:

Insomnia with objective short sleep duration in men is associated with increased mortality, a risk that has been underestimated.

Citation:

Vgontzas AN; Liao D; Pejovic S; Calhoun S; Karataraki M; Basta M; Fernández-Mendoza J; Bixler EO. Insomnia with short sleep duration and mortality: the Penn State Cohort. SLEEP 2010;33(9):1159-1164.     

A double missense variation of the BUB1 gene and a defective mitotic spindle checkpoint in the pancreatic cancer cell line Hs766T

To determine sequence variations of the BUB1 and BUB1B genes in pancreatic cancer, the entire coding regions of the BUB1 and BUB1B genes were sequenced in pancreatic cancer cell lines and xenografts. Although only polymorphic alterations were found in the BUB1B gene, the aneuploid pancreatic cell line Hs766T had two novel missense variants (p.[Y259C;H265N]) in the BUB1 gene. These mutations were on the same allele, accompanied by a wild-type BUB1 allele. This change was not found in other samples, the literature, or 110 additional chromosomes from a reference population. Compared to two cell lines having microsatellite instability (MIN), the TP53 wild-type pancreatic cell line Hs766T had a defective mitotic spindle checkpoint, indicative of a cell line with chromosomal instability (CIN). Evidence that this checkpoint pathway can be abrogated by mutations in the BUB1 gene (Cahill et al., 1998) supports the suggestion the missense mutations of the BUB1 gene in the Hs766T cell line may contribute to its observed mitotic checkpoint defect.     

Dissection of the hyperadhesive phenotype of airway eosinophils in asthma

Asthma is characterized by appearance of eosinophils in the airway. Eosinophils purified from the airway 48 h after segmental antigen challenge are described as exhibiting greater adhesion to albumin-coated surfaces via an unidentified beta2 integrin and increased expression of alphaMbeta2 (CD11b/18) compared with purified blood eosinophils. We have investigated the determinants of this hyperadhesive phenotype. Airway eosinophils exhibited increased reactivity with the CBRM1/5 anti-alphaM activation-sensitive antibody as well as enhanced adhesion to VCAM-1 (CD106) and diverse ligands, including albumin, ICAM-1 (CD54), fibrinogen, and vitronectin. Purified blood eosinophils did not adhere to the latter diverse ligands. Enhanced adhesion of airway eosinophils was blocked by anti-alphaMbeta2. Podosomes, structures implicated in cell movement and proteolysis of matrix proteins, were larger and more common on airway eosinophils adherent to VCAM-1 when compared with blood eosinophils. Incubation of blood eosinophils with IL-5 replicated the phenotype of airway eosinophils. That is, IL-5 enhanced recognition of alphaM by CBRM1/5; stimulated alphaMbeta2-mediated adhesion to VCAM-1, albumin, ICAM-1, fibrinogen, and vitronectin; and increased podosome formation on VCAM-1. Thus, the hyperadhesion of airway eosinophils after antigen challenge is mediated by upregulated and activated alphaMbeta2.     

Age-related spatial learning impairment is unrelated to spinophilin immunoreactive spine number and protein levels in rat hippocampus

Age-related impairments in hippocampus-dependent learning and memory tasks are not associated with a loss of hippocampal neurons, but may be related to alterations in synaptic integrity. Here we used stereological techniques to estimate spine number in hippocampal subfields using immunostaining for the spine-associated protein, spinophilin, as a marker. Quantification of the immunoreactive profiles was performed using the optical disector/fractionator technique. Aging was associated with a modest increase in spine number in the molecular layer of the dentate gyrus and CA1 stratum lacunosum-moleculare. By comparison, spinophilin protein levels in the hippocampus, measured by Western blot analysis, failed to differ as a function of age. Neither the morphological nor the protein level data were correlated with spatial learning ability across individual aged rats. The results extend current evidence on synaptic integrity in the aged brain, indicating that a substantial loss of dendritic spines and spinophilin protein in the hippocampus are unlikely to contribute to age-related impairment in spatial learning.     

The relationship between mental disorders, quality of life, and pregnancy: findings from a nationally representative sample

BACKGROUND: The present study examined health-related quality of life (HRQOL) and the prevalence of mental disorders in pregnant and past-year pregnant women compared to non-pregnant women. METHOD: Data came from the National Epidemiologic Survey on Alcohol and Related Conditions. Three groups of women (ages 18-44) were compared: currently pregnant (n=451), past-year pregnant (n=1061), and not pregnant (n=10,544). Past-year mood, anxiety and substance use disorders were assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version. HRQOL was measured by the Medical Outcomes Study Short Form (SF-12). All analyses included sociodemographics as covariates. RESULTS: Multiple logistic regression analyses showed that pregnant women were less likely than non-pregnant women to have depression and alcohol abuse or dependence; and less likely than past-year pregnant women to have depression and mania. Past-year pregnant women were less likely than non-pregnant women to have social phobia and alcohol dependence or abuse. Multiple linear regression analyses demonstrated that pregnant and non-pregnant women had higher mental component scores than past-year pregnant women. Physical component scores were lower in pregnant women than in non-pregnant and past-year pregnant groups. LIMITATIONS: This was a cross-sectional survey and the causality of relationships cannot be inferred. CONCLUSIONS: Results suggest that pregnant women have a lower likelihood of mental disorder than both non-pregnant and past-year pregnant women.     

Abnormal intestinal histology in neonates with congenital anomalies of the gastrointestinal tract

In animal models, when swallowing is experimentally prevented in utero, bowel length and weight are reduced, and villus height, crypt depth, and villus function are retarded. Little is known about the intestinal histology in infants with gastrointestinal (GI) tract anomalies. We examined the histological architecture of the intestine in neonates with GI anomalies in comparison to that of normal fetuses. Villus height, area, and length and crypt depth of normal fetuses were quantified in the proximal small bowel (n = 11) and measurements compared to those of surgical specimens of neonates with congenital anomalies of the GI tract (n = 16). Villus height and area and lamina propria height and area increased linearly from 8 to 24 weeks of gestation. In infants with anomalies of the GI tract, the villi were blunted and lacked normal histological architecture, the crypts were disorganized, and the crypt depth was significantly decreased (p = 0.004). Enterocyte height and area were significantly greater in neonates with congenital anomalies of the GI tract. The intestinal histology in neonates with congenital anomalies of the GI tract differs significantly from that of normal fetuses.     

Biographical Sketch: Royal Whitman, 1857–1946

This biographical sketch of Royal Whitman corresponds to the historic text, The Classic: A Study of the Weak Foot, with Reference to its Causes, its Diagnosis, and its Cure; with an Analysis of a Thousand Cases of So-Called Flat-Foot, available at DOI .