Prenatal Origins of Poor Sleep in Children

Study Objectives:

We examined whether small body size at birth and prenatal tobacco or alcohol exposure predict poor sleep and more sleep disturbances in children.

Design:

An epidemiologic cohort study of 289 eight-year-old children born at term.

Measurements and results:

Sleep duration and efficiency were measured by actigraphy for 7 consecutive nights (mean = 7.1, SD = 1.2). We used both continuous measures of poor sleep and binary variables of short sleep and low sleep efficiency ( ≤ 10^th percentiles). Parents completed the Sleep Disturbance Scale for Children. Lower birth weight and shorter length at birth were associated with lower sleep efficiency. For every 1-SD decrease in weight and length at birth, the odds for low sleep efficiency increased by 1.7 fold (95% confidence interval [CI]: 1.1 to 2.7) and 2.2 fold (95% CI: 1.3 to 3.7), respectively. For every 1-SD decrease in ponderal index at birth, the risk of parent-reported sleep disorders increased by 1.4 fold (95% CI: 1.0 to 2.0). Moreover, children exposed prenatally to alcohol had a 2.9-fold (95% CI: 1.1 to 7.6) and 3.6-fold (95% CI: 1.3 to 10.0) increased risk for having short sleep and low sleep efficiency, respectively. The associations were not confounded by sex, gestational length, prenatal and perinatal complications, body mass index at 8 years, asthma, allergies, or parental socioeconomic status.

Conclusions:

Poor sleep in children may have prenatal origins. Possible mechanisms include alcohol consumption during pregnancy and other conditions associated with small body size at birth.

Citation:

Pesonen AK; Röaikköonen K; Matthews K; Heinonen K; Paavonen JE; Lahti J; Komsi N; Lemola S; Jöarvenpöaöa AL; Kajantie E; Strandberg T. Prenatal origins of poor sleep in children. SLEEP 2009;32(8):1086-1092.     

Comparison of Diagnostic Methods for Asperger Syndrome

Several different diagnostic sets of criteria exist for Asperger syndrome (AS), but there is no agreement on a gold standard. The aim of this study was to compare four diagnostic sets of criteria for AS: the ICD-10, the DSM-IV, the Gillberg & Gillberg, and the Szatmari criteria. The series consists of 36 children who had been referred to two centers with a tentative diagnosis of AS. The best agreement was between the ICD-10 and the DSM-IV criteria (Kappa coefficient 0.48), and the lowest between the Gillberg & Gillberg and Szatmari criteria (Kappa coefficient -0.21). The poor agreement between these sets of diagnostic criteria compromises the comparability of studies on AS.     

Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in diabetes

OBJECTIVE—Activation of the receptor for advanced glycation end products (RAGE) in diabetic vasculature is considered to be a key mediator of atherogenesis. This study examines the effects of deletion of RAGE on the development of atherosclerosis in the diabetic apoE^−/− model of accelerated atherosclerosis.RESEARCH DESIGN AND METHODS—ApoE^−/− and RAGE^−/−/apoE^−/− double knockout mice were rendered diabetic with streptozotocin and followed for 20 weeks, at which time plaque accumulation was assessed by en face analysis.RESULTS—Although diabetic apoE^−/− mice showed increased plaque accumulation (14.9 ± 1.7%), diabetic RAGE^−/−/apoE^−/− mice had significantly reduced atherosclerotic plaque area (4.9 ± 0.4%) to levels not significantly different from control apoE^−/− mice (4.3 ± 0.4%). These beneficial effects on the vasculature were associated with attenuation of leukocyte recruitment; decreased expression of proinflammatory mediators, including the nuclear factor-κB subunit p65, VCAM-1, and MCP-1; and reduced oxidative stress, as reflected by staining for nitrotyrosine and reduced expression of various NADPH oxidase subunits, gp91phox, p47phox, and rac-1. Both RAGE and RAGE ligands, including S100A8/A9, high mobility group box 1 (HMGB1), and the advanced glycation end product (AGE) carboxymethyllysine were increased in plaques from diabetic apoE^−/− mice. Furthermore, the accumulation of AGEs and other ligands to RAGE was reduced in diabetic RAGE^−/−/apoE^−/− mice.CONCLUSIONS—This study provides evidence for RAGE playing a central role in the development of accelerated atherosclerosis associated with diabetes. These findings emphasize the potential utility of strategies targeting RAGE activation in the prevention and treatment of diabetic macrovascular complications.The receptor for advanced glycation end products (RAGE) is a multiligand cell surface molecule belonging to the immunoglobulin superfamily (1). It is expressed as full-length, N-truncated, and C-truncated isoforms, generated in humans by alternative splicing (2). Activation of the full-length RAGE receptor has been implicated in a range of chronic diseases, including various diabetic complications and atherosclerosis (1). In particular, studies in RAGE^−/− mice that carry the dominant-negative form of the receptor (2–6) and in RAGE-overexpressing mice (7) have confirmed an important role of RAGE activation in the development of diabetic nephropathy, neuropathy, and impaired angiogenesis. RAGE activation has also been implicated in the acceleration of atherosclerotic lesion formation as well as in the maintenance of proinflammatory and prothrombotic mechanisms, characteristic of diabetes-accelerated atherosclerosis (8,9). RAGE also represents an important mediator of oxidative stress in diabetes. Activation of RAGE in vitro leads to increased NADPH oxidase expression, mitochondrial oxidase activity, and downregulation of endogenous antioxidant activity (10,11). RAGE^−/− mice have a suppression of neointimal proliferation after externally induced arterial injury in the absence of diabetes (12). Moreover, blockade of RAGE-dependent signaling by soluble RAGE (sRAGE) has been shown to inhibit the progression of atherosclerotic changes (8,9) and kidney disease (3) in diabetic mice, possibly by suppressing the activation of nuclear factor-κB (NF-κB) activation and inflammatory cytokine expression. The present study examined the role of RAGE in the development of diabetes-accelerated atherosclerosis in a model of insulin deficiency, the streptozotocin-induced diabetic RAGE^−/−/apoE^−/− mouse. Our aim was to determine the effect of global RAGE deficiency, which includes absence of both the full-length receptor and endogenous sRAGE on the development of vascular lesions in the presence and absence of diabetes. Furthermore, key mediators of the atherosclerotic process in diabetes were examined, and the effects on these pathways were assessed in these RAGE-deficient mice.     

Type 1 cytokine response and treatment outcome of genital HPV lesions.

OBJECTIVES: To determine the role of type 1 cytokines as predictors of response to treatment of genital HPV lesions with laser ablation with or without adjuvant systemic interferon alpha 2b (IFN-alpha). METHODS: Measurement of serum interleukin 2 (IL-2), IL-2 soluble receptor alpha (sIL-2 alpha), interferon gamma, and human papilloma virus (HPV) DNA in patients undergoing treatment of genital HPV lesions with carbon dioxide laser and systemic IFN-alpha. A randomised, placebo controlled study of 92 cases with 6 months of follow up. RESULTS: High IL-2/sIL-2 alpha was associated with 60% to 70% protection against recurrences both in the IFN-alpha and placebo groups (OR = 0.4, 90%, CI 0.1-2.5; OR = 0.3, 90% CI 0.0-1.8, respectively). Diagnostic phase serum IL-2 predicted favourable outcome (OR = 0.2, 90% CI 0.0-1.0) in women with high load of HPV DNA or HPV 16/18 DNA regardless of the adjuvant therapy. CONCLUSIONS: Serum IL-2 determinations may identify women with good prognosis following laser ablation of genital HPV lesions.     

A nationwide sentinel clinic survey of chlamydia trachomatis infection in Finland

BACKGROUND: Chlamydia trachomatis has been recognized as a major sexually transmitted infection in North America and Western Europe during the past two decades. The incidence of C trachomatis in Finland has been continuously high throughout the 1990s. OBJECTIVES: As the epidemic of C trachomatis infection continues in Finland, there is a need to obtain up-to-date information on the prevalence and patient profiles in the planning of preventive strategies. METHODS: A nationwide sentinel clinic network consisting of seven sexually transmitted disease (STD) and five general student health clinics was established in 1995. Data were collected during a 3-year period (1995-1997) from 3,686 patients with and 32,230 patients without C trachomatis using a self-administered questionnaire. RESULTS: The prevalence of chlamydia was 8.4% in the STD clinics and 5.3% in the general clinics; 90% of the infections were endemic. The prevalence was highest in the youngest age group (15-19 years; 16% in females, 14% in males). The patients with chlamydia were significantly younger (mean age: men 26.6 years, women 23.7 years) than those without chlamydia. Women with chlamydia used oral contraceptives or intrauterine devices (IUD) significantly more often (59%) than women without chlamydia (42%). A high number of sex partners and a history of previous chlamydia during the preceding 12 months were also risk factors. Men contracted chlamydia frequently from a casual partner (61%) but rarely from a commercial sex worker (2%). For women, the source partner was most often a regular one (61%). The median time from exposure to attendance was 34 days, and was highest when the source partner was a spouse. One third of the patients could have spread chlamydia to a new partner before the diagnosis. CONCLUSIONS: C trachomatis infection is spread all over Finland, and the risk factors include younger age, high number of sex partners, and use of oral contraceptives or IUDs. Source partner analysis focused attention on the importance of transmission from regular partners, especially in women. The time from transmission to diagnosis was long, and any effort to shorten this period would be an effective preventive strategy.     

Characterization of androgen-regulated expression of CYP3A5 in human prostate

Testosterone is needed for the growth and development of the prostate. Androgen deprivation therapy is used for the treatment of prostate cancer. CYP3A5 is a human drug-metabolizing cytochrome P450 enzyme that metabolizes testosterone to the inactive 6beta-hydroxylated metabolite. We identified CYP3A5 as a novel androgen-regulated gene in human prostate by GeneChip analysis of human prostate tissues obtained from patients 3 days after therapeutic castration and from control patients. We further showed androgen induction of CYP3A5 messenger RNA (mRNA) in LNCaP prostate cancer cell line. Immunoblotting studies revealed CYP3A5 protein expression in all prostate samples studied. Immunohistochemistry and in situ hybridization was used for localization of CYP3A5 expression in prostate tissue. CYP3A5 was detected both in luminal and in basal epithelial cells of human prostate. Androgen response element was identified in the CYP3A5 proximal promoter and in electrophoretic mobility shift assay androgen receptor was found to bind this element. Androgen induction was abolished by mutation of the response element. We suggest that CYP3A5 is a part of an autoregulatory feedback loop controlling prostate cell exposure to androgens.     

Heat shock preconditioning modulates proliferation and apoptosis after superficial injury in isolated guinea pig gastric mucosa via an eicosanoid and protein synthesis-dependent mechanism

AIM: In restitution after superficial injury of the gastric mucosa, the epithelial continuity is restored by cellular migration. We have shown that heat shock preconditioning inhibits restitution after superficial injury. This study investigates the effect of heat shock preconditioning on tissue proliferation and apoptosis. EXPERIMENTAL DESIGN: Paired guinea pig gastric mucosae were mounted and perfused in Ussing chambers (37 degrees C). After heat shock preconditioning (42 degrees C) (30 min) and normothermic recovery (37 degrees C) (150 min) or normothermic perfusion, a superficial injury was induced by luminal exposure to 1.25 mol/L NaCl (5 min) followed by a 3 h restitution. During perfusion, the mucosa was exposed to 30 micromol/L arachidonic acid (AA) to enhance heat shock response, to 50 micromol/L quercetin (Q) to inhibit the metabolism of arachidonic acid via lipoxygenases, to 50 micromol/L indomethacin (In) to inhibit the metabolism of arachidonic acid via cyclo-oxygenases, or to 150 micromol/L cycloheximide (CHX) to inhibit de novo protein synthesis. After the experiment the mucosa was prepared for immunohistochemical analysis of the expression of Mib-1 proliferation antigen and pro-apoptotic protein Bax. RESULTS: Heat shock decreased Mib-1/Bax ratio and this effect was maintained after superficial injury and exposure to Q, to AA+CHX or to In+CHX. Exposure to CHX, to AA, to In+Q, to In+AA, In+AA+Q or to In+AA+CHX, however, blocked the effect of heat shock preconditioning. The decreasing effect of heat shock preconditioning on Mib-1/Bax ratio could be reversed by exposure to AA+Q or to In. CONCLUSION: The heat-preconditioning-induced effects on the mucosa are reversible and sensitive to exogenous pharmacological modulation. Heat shock preconditioning inhibits proliferation of superficially injured isolated gastric mucosa by a mechanism involving eicosanoid pathways and de novo protein synthesis.     

Prepregnancy risk factors for placental abruption

BACKGROUND: To define the prepregnancy risk factors for placental abruption. METHODS: One hundred and ninety-eight women with placental abruption and 396 control women without placental abruption were retrospectively identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Relevant historical and clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors. RESULTS: The overall incidence of placental abruption was 0.42%. Placental abruption recurred in 8.8% of the cases. The independent risk factors were smoking (OR 1.7; 95% CI 1.1, 2.7), uterine malformation (OR 8.1; 1.7, 40), previous cesarean section (OR 1.7; 1.1, 2.8), and history of placental abruption (OR 4.5; 1.1, 18). CONCLUSIONS: Although univariate analysis identified many risk factors, only smoking, uterine malformation, previous cesarean section, and history of placental abruption remained significant after multivariate analysis, increasing the risk of placental abruption in subsequent pregnancy. It may be possible to approximate the risk for placental abruption based on these simple prepregnancy risk factors.     

T1ρ dispersion imaging of head and neck tumors: A comparison to spin lock and magnetization transfer techniques

The potential of T1ρ dispersion, spin lock (SL), and magnetization transfer (MT) techniques to differentiate benign and malignant head and neck tumors was evaluated. Twenty-four patients with pathologically verified head and neck tumors were studied with a .1-T MR imager. T1ρ dispersion effect was defined as 1 — (intensity with lower locking field amplitude/intensity with higher locking field amplitude). T1ρ dispersion effects were higher for malignant than benign tumors (P = .001). With T1ρ dispersion effect .14 as the threshold, sensitivity for detecting a malignant tumor was 91%, specificity was 77%, and accuracy was 83%. A strong correlation between T1ρ dispersion effects and SL effects and between T1ρ dispersion effects and MT effects in the head and neck tumors was found (r = .87, P < .001 and r = .90, P < .001, respectively). High T1ρ dispersion effects are not specific indicators of malignancy, because chronic infections, some benign tumors, and malignancies may overlap. Low T1ρ dispersion effect values are characteristic of a benign tumor.     

Chronic rejection of rat renal allograft

Chronic allograft rejection is both a clinical and a histopathological diagnosis. Until recently, the histological definition of chronic renal allograft rejection was based on clinical diagnostic biopsies, where the evidence was partially obscured by recurrence of the original renal disease, and/or by administration of immunosuppressive drugs. In this communication, we present an experimental rat model for chronic renal allograft rejection, devoid of recurrence of the original disease. By comparing allografts to similarly immunosuppressed syngeneic transplants, we define which histological features should be attributed to chronic rejection and which to cyclosporin nephrotoxicity. Rat renal transplants were performed from DA (Ag-B4, RT1^av1) to WF strain (Ag-B2, RT1^u) or, for control, to DA strain, and immunosuppressed for 2 or 3 weeks with cyclosporin using a variety of different dosages. The animals were monitored weekly for serum creatinine levels and for blood cyclosporin concentrations, and core needle biopsies were performed on the grafts at regular intervals. At 3 months post-transplantation the animals were sacrificed and a complete histopathological evaluation was performed. Thirty-one histological variables were scored blindly by two investigators and separately for the graft interstitium, glomeruli, tubuli, and the graft vasculature. The following histological alterations were significantly more prominent in allografts than in similarly immunosuppressed syngeneic transplants: the intensity of interstitial inflammation, particularly the degree of pyroninophilia within the inflammatory cell population; the extent of glomerular mesangial matrix increase, basement membrane thickening, and glomerular sclerosis; the increase in the vascular intimal thickness affecting in particular the first and second order branches of the renal artery; and the obliteration of the graft vasculature. These alterations were considered as being primarily due to chronic rejection. In contrast, the extent of interstitial fibrosis and the extent of tubular changes, including tubular epithelial vacuolation, epithelial atrophy, and tubular basement membrane changes, were not significantly different in the allografts as compared to the syngeneic controls. These alterations were attributed primarily to cyclosporin nephrotoxicity. Serial monitoring of the grafts by needle biopsies clarified the sequence of events in the development of the chronic alterations in the transplant. The first event, as expected, was tubulointerstitial pyroninophilic inflammation, resembling that of acute episodes of rejection. This was significantly stronger and appeared earlier in allografts immunosuppressed for 2 rather than for 3 weeks. Vascular alterations developed next. The last to develop were the glomerular lesions.