Sleep interventions for children with attention deficit hyperactivity disorder (ADHD): A systematic literature review.

OBJECTIVE/BACKGROUND: Healthy sleep is particularly important for children with attention deficit hyperactivity disorder (ADHD), as sleep disturbances might aggravate disease symptoms. This review aims to synthesize and report evidence on the effectiveness of sleep interventions in increasing sleep, quality of life (QoL), and ADHD symptoms among children with ADHD. PATIENTS/METHODS: The systematic literature review follows the Cochrane Collaboration methodology recommendations for literature reviews. Four databases were used based on the population, intervention, control and outcome (PICO) framework. Controlled trials with minimum 20 children in each group, aged 6-18, and published from 2005 and onwards were included. Results from the studies were reported in forest plots and three of the seven review outcomes were synthesized in meta-analyses. RESULTS: The search identified 7710 records; of which 4808 abstracts were screened. After fulltext-screening of 99 papers, eight papers from five studies were included. The studies included behavioral sleep interventions and pharmacological interventions using melatonin and eszopiclone. For six of the seven outcomes, the effect sizes were small to moderate and the certainty of the evidence was low. For one outcome, sleep disturbances, the effect size was a moderate -0.49 standardized mean differences (95% confidence interval -0.65;-0.33), with a moderate certainty of evidence for the behavioral interventions for children aged 5-13 years with ADHD. CONCLUSIONS: This review identified few and heterogeneous studies. A moderate certainty of evidence for a moderate effect size was only obtained for sleep disturbances from the behavioral interventions. A low certainty of the evidence for a moderate effect size was found for the total sleep time from the pharmacological intervention using melatonin and one behavioral intervention, which indicates that these sleep interventions impact sleep quantity and quality among children with ADHD.

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.

BACKGROUND/OBJECTIVES: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. SUBJECTS/METHODS: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. RESULTS: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001). CONCLUSIONS: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance.

Proteasome inhibition and oxidative reactions disrupt cellular homeostasis during heme stress.

Dual control of cellular heme levels by extracellular scavenger proteins and degradation by heme oxygenases is essential in diseases associated with increased heme release. During severe hemolysis or rhabdomyolysis, uncontrolled heme exposure can cause acute kidney injury and endothelial cell damage. The toxicity of heme was primarily attributed to its pro-oxidant effects; however additional mechanisms of heme toxicity have not been studied systematically. In addition to redox reactivity, heme may adversely alter cellular functions by binding to essential proteins and impairing their function. We studied inducible heme oxygenase (Hmox1)-deficient mouse embryo fibroblast cell lines as a model to systematically explore adaptive and disruptive responses that were triggered by intracellular heme levels exceeding the homeostatic range. We extensively characterized the proteome phenotype of the cellular heme stress responses by quantitative mass spectrometry of stable isotope-labeled cells that covered more than 2000 individual proteins. The most significant signals specific to heme toxicity were consistent with oxidative stress and impaired protein degradation by the proteasome. This ultimately led to an activation of the response to unfolded proteins. These observations were explained mechanistically by demonstrating binding of heme to the proteasome that was linked to impaired proteasome function. Oxidative heme reactions and proteasome inhibition could be differentiated as synergistic activities of the porphyrin. Based on the present data a novel model of cellular heme toxicity is proposed, whereby proteasome inhibition by heme sustains a cycle of oxidative stress, protein modification, accumulation of damaged proteins and cell death.

Beneficial metabolic effects of the Malaysian herb Labisia pumila var. alata in a rat model of polycystic ovary syndrome.

AIM OF THE STUDY: New options are needed to prevent and treat metabolic disorders associated with polycystic ovary syndrome (PCOS). Labisia pumila var. alata (LPva)-a Malaysian herb thought to have phytoestrogenic effects-has shown promise in reducing body weight gain in ovariectomized rats. In this study, we investigated the effect of LPva on body composition and metabolic features in female rats treated continuously with dihydrotestosterone, starting before puberty, to induce PCOS. MATERIAL AND METHODS: At 9 weeks of age, the PCOS rats were randomly subdivided into two groups; PCOS LPva and PCOS control. PCOS LPva rats received a daily oral dose of LPva (50mg/kg body weight), dissolved in 1 ml of deionised water, for 4-5 weeks. PCOS controls received 1 ml of deionised water on the same schedule. RESULTS: LPva increased uterine weight (27%) and insulin sensitivity (36%) measured by euglycemic hyperinsulinemic clamp. Plasma resistin levels were increased and lipid profile was improved in LPva rats. In adipose tissue, LPva decreased leptin mRNA expression but did not affect expression of resistin and adiponectin. No effects on body composition, adipocyte size, or plasma leptin levels were observed. CONCLUSION: LPva increases uterine weight, indicating estrogenic effects, and improves insulin sensitivity and lipid profile in PCOS rats without affecting body composition.

Influence of herring (Clupea harengus) and herring fractions on metabolic status in rats fed a high energy diet.

AIM: Few dietary studies have looked beyond fish oil to explain the beneficial metabolic effects of a fish-containing diet. Our aim was to study whether addition of herring, or sub-fractions of herring, could counteract negative metabolic effects known to be induced by a high-fat, high-sugar diet. METHODS: Rats were given six different diets: standard pellets; high energy diet with chicken mince (HiE control); high energy diet with herring mince (HiE herring); and high energy diet with chicken mince and either herring oil (HiE herring oil), herring press juice, PJ (HiE PJ) or herring low molecular weight PJ (HiE LMW-PJ). Factors associated with the metabolic syndrome were measured. RESULTS: There were no differences in energy intake or body weight between the groups, but animals fed high energy diets had a higher body fat content compared with the pellet group, although not statistically significant in all groups. Mesenteric adipocyte size was smaller in the HiE herring oil group compared with the HiE control. Glucose clamp studies showed that, compared with the pellet group, the HiE control and HiE herring diets, but not the HiE herring oil diet, induced insulin resistance. Addition of herring or herring oil to the high energy diet decreased total cholesterol levels, triacylglycerols and the atherogenic index compared with the HiE control group. CONCLUSIONS: The results suggest that addition of herring or herring oil counteracts negative effects on blood lipids induced by a high energy diet. The lipid component of herring thus seems to be responsible for these beneficial effects.

Local-scale genetic structure in the peatmoss Sphagnum fuscum.

Sphagnum (peatmoss) dominates huge areas of the Northern Hemisphere and acts as a significant carbon sink on a global scale, yet little is known about the genetic structure of Sphagnum populations. We investigated genetic structure within a population of the common peatmoss Sphagnum fuscum, to assess local patterns of genetic diversity and the spatial extent of clones. One hundred seventeen shoots were sampled from five transects in Fuglmyra, central Norway, and sequenced for three anonymous DNA regions. Five neighbourhood patches were marked along each transect, and from each patch, five stems were sampled for molecular analyses. Seventeen haplotypes could be distinguished and two major groups of haplotypes differed by 12 mutational steps. The two major haplotype groups differed significantly in microhabitat association along the distance to groundwater table and the pH gradients, indicating microhabitat differentiation. The haplotypes within these groups were all genetically similar, differing by one or two mutations. The most common haplotype occurred in four transects separated by 250-m distance. Most of the molecular variation in the population was found among transects, and within patches. Large dominating clones within each transect resulted in low variation explained by the among-patch-within-transect component of spatial structure. Mutation appears to account for a larger proportion of the population variation than recombination. Within the population, vegetative growth and asexual reproduction from gametophyte fragments dominate as the main reproductive mode.

Thiol redox control via thioredoxin and glutaredoxin systems.

The Trx (thioredoxin) and Grx (glutaredoxin) systems control cellular redox potential, keeping a reducing thiol-rich intracellular state, which on generation of reactive oxygen species signals through thiol redox control mechanisms. Here, we give a brief overview of the human Trx and Grx systems. The main part focuses on our current knowledge about mitochondrial Grx2, which facilitates mitochondrial redox homoeostasis during oxidative stress-induced apoptosis.

Genetic differentiation and habitat preference of flowering-time variants within Gymnadenia conopsea.

Using fast-evolving microsatellites, more slowly evolving ITS markers and performing habitat analyses, we demonstrated a drastic genetic divergence and significant habitat differentiation between early- and late-flowering variants of plants morphologically belonging to Gymnadenia conopsea ssp conopsea. The two phenological variants can either be found in separate or in mixed populations. Information from microsatellite markers and ITS sequences indicated the occurrence of an early historical split between the two flowering-time variants, a split that has been maintained until the present time even within sympatric populations. Early-flowering variants were also far more genetically diverse, had more alleles per microsatellite locus and a wider habitat amplitude than late-flowering variants. As a comparison, we included G. odoratissima in the sequencing study. We found G. odoratissima to be most closely related to the early-flowering type. This indicates a more ancient divergence event between the two flowering-time variants within G. conopsea ssp conopsea than between the two different species G. odoratissima and the early-flowering variant of G. conopsea. Possible explanations to the results arrived at and possible mechanisms maintaining the genetic separation are discussed.

ABH isoantigens, histology and DNA ploidy in 36 consecutive patients with transitional cell bladder cancer. Status of tumor and biopsies taken from visually normal urothelium.

Tumors and biopsies from visibly normal urothelium in 36 consecutive patients with transitional cell bladder carcinoma were analysed for histological pathology, DNA ploidy and ABH isoantigens. Tumor isoantigen deletion correlated strongly with malignant histology (p = 0.016) and aneuploidy (p = 0.005). In 4/12 patients with ABH isoantigens present on the tumor, and in 6/8 with isoantigens absent, isoantigen changes were found in normal looking urothelium, usually with normal histology and ploidy. It was concluded that the ABH isoantigen change was an early event in bladder carcinoma.

Long-term effects of papillotomy.

Forty-three patients who were papillotomied according to Doubilet were followed up for 20-25 years after the papillotomy in an attempt to predict the long-term effects of endoscopic papillotomy (EPT). The indications for the initial papillotomy was common bile duct stones in 20 patients, and elevated serum amylase in 23. The papillotomy was performed in conjunction with a cholecystectomy. No negative effects were found at follow-up, and this study therefore seems to show that the long-term risks of EPT are minimal.