Dose-response associations between screen time and overweight among youth

Objective. To examine dose-response associations between screen time and overweight, independent of physical activity and dietary intake.

Methods. Participants were 580 Dutch youth (13 years; 48% boys). Body mass index, waist circumference and skinfold thickness at four sites determined weight status. Questionnaires examined television viewing and computer use, participation in organized sport and high caloric snack and sugar-containing beverage consumption.

Results. There were no significant associations among boys. Compared with girls spending less than two hours/day in screen time, those who spent three to four hours/day were more likely to be classified as overweight by waist circumference (odds ratio [OR]=3.4; 95% confidence intervals [CI]=1.1-10.7; p=0.03), and this likelihood increased substantially among those spending more than four hours/day (OR=5.5; 95% CI=2.1-14.1; p≤0.0001).

Conclusions. Girls who spend three or more hours/day in screen time are at increased risk of being classified as overweight by waist circumference.

Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet

The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-α, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-β, and PPAR-γ) and BT (C/EBP-β), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-γ genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.

Gut health immunomodulatory and anti-inflammatory functions of gut enzyme digested high protein micro-nutrient dietary supplement-Enprocal

Background: Enprocal is a high-protein micro-nutrient rich formulated supplementary food designed to meet the nutritional needs of the frail elderly and be delivered to them in every day foods. We studied the potential of Enprocal to improve gut and immune health using simple and robust bioassays for gut cell proliferation, intestinal integrity/permeability, immunomodulatory, anti-inflammatory and anti-oxidative activities. Effects of Enprocal were compared with whey protein concentrate 80 (WPC), heat treated skim milk powder, and other commercially available milk derived products.

Results: Enprocal (undigested) and digested (Enprocal D) selectively enhanced cell proliferation in normal human intestinal epithelial cells (FHs74-Int) and showed no cytotoxicity. In a dose dependent manner Enprocal induced cell death in Caco-2 cells (human colon adencarcinoma epithelial cells). Digested Enprocal (Enprocal D: gut enzyme cocktail treated) maintained the intestinal integrity in transepithelial resistance (TEER) assay, increased the permeability of horseradish peroxidase (HRP) and did not induce oxidative stress to the gut epithelial cells. Enprocal D upregulated the surface expression of co-stimulatory (CD40, CD86, CD80), MHC I and MHC II molecules on PMA differentiated THP-1 macrophages in coculture transwell model, and inhibited the monocyte/lymphocyte (THP-1/Jurkat E6-1 cells)-epithelial cell adhesion. In cytokine secretion analyses, Enprocal D down-regulated the secretion of proinflammatory cytokines (IL-1β and TNF-α) and up-regulated IFN-γ, IL-2 and IL-10.

Conclusion: Our results indicate that Enprocal creates neither oxidative injury nor cytotoxicity, stimulates normal gut cell proliferation, up regulates immune cell activation markers and may aid in the production of antibodies. Furthermore, through downregulation of proinflammatory cytokines, Enprocal appears to be beneficial in reducing the effects of chronic gut inflammatory diseases such as inflammatory bowel disease (IBD). Stimulation of normal human fetal intestinal cell proliferation without cell cytotoxicity indicates it may also be given as infant food particularly for premature babies.

Determination of intracellular glutathione and glutathione disulfide using high performance liquid chromatography with acidic potassium permanganate chemiluminescence detection

Measurement of glutathione (GSH) and glutathione disulfide (GSSG) is a crucial tool to assess cellular redox state. Herein we report a direct approach to determine intracellular GSH based on a rapid chromatographic separation coupled with acidic potassium permanganate chemiluminescence detection, which was extended to GSSG by incorporating thiol blocking and disulfide bond reduction. Importantly, this simple procedure avoids derivatisation of GSH (thus minimising auto-oxidation) and overcomes problems encountered when deriving the concentration of GSSG from ‘total GSH’. The linear range and limit of detection for both analytes were 7.5 × 10−7 to 1 × 10−5 M, and 5 × 10−7 M, respectively. GSH and GSSG were determined in cultured muscle cells treated for 24 h with glucose oxidase (0, 15, 30, 100, 250 and 500 mU mL−1), which exposed them to a continuous source of reactive oxygen species (ROS). Both analyte concentrations were greater in myotubes treated with 100 or 250 mU mL−1 glucose oxidase (compared to untreated controls), but were significantly lower in myotubes treated with 500 mU mL−1 (p < 0.05), which was rationalised by considering measurements of H2O2 and cell viability. However, the GSH/GSSG ratio in myotubes treated with 100, 250 and 500 mU mL−1 glucose oxidase exhibited a dose-dependent decrease that reflected the increase in intracellular ROS.

Variation in the gene coding for the M5 muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction : evidence from a prospective population based cohort study of young adults

Background: The mesolimbic structures of the brain are important in the anticipation and perception of reward. Moreover, many drugs of addiction elicit their response in these structures. The M5 muscarinic receptor (M5R) is expressed in dopamine-containing neurones of the substantia nigra pars compacta and ventral tegmental area, and regulates the release of mesolimbic dopamine. Mice lacking M5R show a substantial reduction in both reward and withdrawal responses to morphine and cocaine. The CHRM5, the gene that codes for the M5R, is a strong biological candidate for a role in human addiction. We screened the coding and core promoter sequences of CHRM5 using denaturing high performance liquid chromatography to identify common polymorphisms. Additional polymorphisms within the coding and core promoter regions that were identified through dbSNP were validated in the test population. We investigated whether these polymorphisms influence substance dependence and dose in a cohort of 1947 young Australians.

Results: Analysis was performed on 815 participants of European ancestry who were interviewed at wave 8 of the cohort study and provided DNA. We observed a 26.8% increase in cigarette consumption in carriers of the rs7162140 T-allele, equating to 20.1 cigarettes per week (p=0.01). Carriers of the rs7162140 T-allele were also found to have nearly a 3-fold increased risk of developing cannabis dependence (OR=2.9 (95%CI 1.1-7.4); p=0.03).

Conclusion: Our data suggest that variation within the CHRM5 locus may play an important role in tobacco and cannabis but not alcohol addiction in European ancestry populations. This is the first study to show an association between CHRM5 and substance use in humans. These data support the further investigation of this gene as a risk factor in substance use and dependence.

The high prevalence of vitamin D insufficiency across Australian populations is only partly explained by season and latitude

Background Inadequate sun exposure and dietary vitamin D intake can result in vitamin D insufficiency. However, limited data are available on actual vitamin D status and predictors in healthy individuals in different regions and by season.

Methods We compared vitamin D status [25-hydroxyvitamin D; 25(OH)D] in people < 60 years of age using data from cross-sectional studies of three regions across Australia: southeast Queensland (27°S; 167 females and 211 males), Geelong region (38°S; 561 females), and Tasmania (43°S; 432 females and 298 males).

Results The prevalence of vitamin D insufficiency (≤ 50 nmol/L) in women in winter/spring was 40.5% in southeast Queensland, 37.4% in the Geelong region, and 67.3% in Tasmania. Season, simulated maximum daily duration of vitamin D synthesis, and vitamin D effective daily dose each explained around 14% of the variation in 25(OH)D. Although latitude explained only 3.9% of the variation, a decrease in average 25(OH)D of 1.0 (95% confidence interval, 0.7–1.3) nmol/L for every degree increase in latitude may be clinically relevant. In some months, we found a high insufficiency or even deficiency when sun exposure protection would be recommended on the basis of the simulated ultraviolet index.

Conclusion Vitamin D insufficiency is common over a wide latitude range in Australia. Season appears to be more important than latitude, but both accounted for less than one-fifth of the variation in serum 25(OH)D levels, highlighting the importance of behavioral factors. Current sun exposure guidelines do not seem to fully prevent vitamin D insufficiency, and consideration should be given to their modification or to pursuing other means to achieve vitamin D adequacy.

Dose-dependent increases in heart rate variability and arterial compliance in overweight and obese adults with DHA-rich fish oil supplementation

Heart rate (HR) variability and large arterial compliance can be improved using fish oils. DHA, a component of fish oil, has cardiovascular health benefits, but its effect on HR variability (HRV) and arterial compliance is yet to be quantified. Sixty-seven overweight or obese adults (thirty-six males and thirty-one females; 53 (sem 2) year; BMI 31·7 (sem 1·1) kg/m²) were randomly allocated to consume either 6 g/d sunola oil (control; n 17), fish oil (260 mg DHA+60 mg EPA per g) at doses of 2 g/d (n 16), 4 g/d (n 17) or 6 g/d (n 17). Blood pressure, HR and compliance of large and small arteries were measured while supine at baseline and after 12 weeks in all participants, and HRV was assessed in a subgroup of forty-six participants. There was no effect of fish oil on blood pressure, small artery compliance or HR. However, the low frequency:high frequency ratio of HRV decreased with increasing doses of fish oil (r − 0·34, P = 0·02), while large artery compliance increased (r 0·34, P = 0·006). Moreover, the changes in these biomarkers were significantly correlated (r − 0·31, P = 0·04) and may reflect fish oil-induced improvements in arterial function and cardiac autonomic regulation.

Identification of unprecedented anticancer properties of high molecular weight biomacromolecular complex containing bovine lactoferrin (HMW-bLf)

With the successful clinical trials, multifunctional glycoprotein bovine lactoferrin is gaining attention as a safe nutraceutical and biologic drug targeting cancer, chronic-inflammatory, viral and microbial diseases. Interestingly, recent findings that human lactoferrin oligomerizes under simulated physiological conditions signify the possible role of oligomerization in the multifunctional activities of lactoferrin molecule during infections and in disease targeting signaling pathways. Here we report the purification and physicochemical characterization of high molecular weight biomacromolecular complex containing bovine lactoferrin (≥250 kDa), from bovine colostrum, a naturally enriched source of lactoferrin. It showed structural similarities to native monomeric iron free (Apo) lactoferrin (∼78-80 kDa), retained anti-bovine lactoferrin antibody specific binding and displayed potential receptor binding properties when tested for cellular internalization. It further displayed higher thermal stability and better resistance to gut enzyme digestion than native bLf monomer. High molecular weight bovine lactoferrin was functionally bioactive and inhibited significantly the cell proliferation (p<0.01) of human breast and colon carcinoma derived cells. It induced significantly higher cancer cell death (apoptosis) and cytotoxicity in a dose-dependent manner in cancer cells than the normal intestinal cells. Upon cellular internalization, it led to the up-regulation of caspase-3 expression and degradation of actin. In order to identify the cutting edge future potential of this bio-macromolecule in medicine over the monomer, its in-depth structural and functional properties need to be investigated further.

Effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system in individuals at ultra-high risk of psychosis

BACKGROUND: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). METHOD: In 64 help-seeking UHR-individuals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. RESULTS: In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. CONCLUSION: Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness.

Increased hypoxic dose after training at low altitude with 9h per night at 3000m normobaric hypoxia

This study examined effects of low altitude training and a live-high: train-low protocol (combining both natural and simulated modalities) on haemoglobin mass (Hbmass), maximum oxygen consumption (VO2max), time to exhaustion, and submaximal exercise measures. Eighteen elite-level race-walkers were assigned to one of two experimental groups; lowHH (low Hypobaric Hypoxia: continuous exposure to 1380 m for 21 consecutive days; n = 10) or a combined low altitude training and nightly Normobaric Hypoxia (lowHH+NHnight: living and training at 1380 m, plus 9 h.night-1 at a simulated altitude of 3000 m using hypoxic tents; n = 8). A control group (CON; n = 10) lived and trained at 600 m. Measurement of Hbmass, time to exhaustion and VO2max was performed before and after the training intervention. Paired samples t-tests were used to assess absolute and percentage change pre and post-test differences within groups, and differences between groups were assessed using a one-way ANOVA with least significant difference post-hoc testing. Statistical significance was tested at p < 0.05. There was a 3.7% increase in Hbmass in lowHH+NHnight compared with CON (p = 0.02). In comparison to baseline, Hbmass increased by 1.2% (±1.4%) in the lowHH group, 2.6% (±1.8%) in lowHH+NHnight, and there was a decrease of 0.9% (±4.9%) in CON. VO2max increased by ~4% within both experimental conditions but was not significantly greater than the 1% increase in CON. There was a ~9% difference in pre and post-intervention values in time to exhaustion after lowHH+NH-night (p = 0.03) and a ~8% pre to post-intervention difference (p = 0.006) after lowHH only. We recommend low altitude (1380 m) combined with sleeping in altitude tents (3000 m) as one effective alternative to traditional altitude training methods, which can improve Hbmass.

Midazolam for sedation before procedures

BACKGROUND: Midazolam is used for sedation before diagnostic and therapeutic medical procedures. It is an imidazole benzodiazepine that has depressant effects on the central nervous system (CNS) with rapid onset of action and few adverse effects. The drug can be administered by several routes including oral, intravenous, intranasal and intramuscular. OBJECTIVES: To determine the evidence on the effectiveness of midazolam for sedation when administered before a procedure (diagnostic or therapeutic). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL to January 2016), MEDLINE in Ovid (1966 to January 2016) and Ovid EMBASE (1980 to January 2016). We imposed no language restrictions. SELECTION CRITERIA: Randomized controlled trials in which midazolam, administered to participants of any age, by any route, at any dose or any time before any procedure (apart from dental procedures), was compared with placebo or other medications including sedatives and analgesics. DATA COLLECTION AND ANALYSIS: Two authors extracted data and assessed risk of bias for each included study. We performed a separate analysis for each different drug comparison. MAIN RESULTS: We included 30 trials (2319 participants) of midazolam for gastrointestinal endoscopy (16 trials), bronchoscopy (3), diagnostic imaging (5), cardioversion (1), minor plastic surgery (1), lumbar puncture (1), suturing (2) and Kirschner wire removal (1). Comparisons were: intravenous diazepam (14), placebo (5) etomidate (1) fentanyl (1), flunitrazepam (1) and propofol (1); oral chloral hydrate (4), diazepam (2), diazepam and clonidine (1); ketamine (1) and placebo (3); and intranasal placebo (2). There was a high risk of bias due to inadequate reporting about randomization (75% of trials). Effect estimates were imprecise due to small sample sizes. None of the trials reported on allergic or anaphylactoid reactions. Intravenous midazolam versus diazepam (14 trials; 1069 participants)There was no difference in anxiety (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.39 to 1.62; 175 participants; 2 trials) or discomfort/pain (RR 0.60, 95% CI 0.24 to 1.49; 415 participants; 5 trials; I² = 67%). Midazolam produced greater anterograde amnesia (RR 0.45; 95% CI 0.30 to 0.66; 587 participants; 9 trials; low-quality evidence). Intravenous midazolam versus placebo (5 trials; 493 participants)One trial reported that fewer participants who received midazolam were anxious (3/47 versus 15/35; low-quality evidence). There was no difference in discomfort/pain identified in a further trial (3/85 in midazolam group; 4/82 in placebo group; P = 0.876; very low-quality evidence). Oral midazolam versus chloral hydrate (4 trials; 268 participants)Midazolam increased the risk of incomplete procedures (RR 4.01; 95% CI 1.92 to 8.40; moderate-quality evidence). Oral midazolam versus placebo (3 trials; 176 participants)Midazolam reduced pain (midazolam mean 2.56 (standard deviation (SD) 0.49); placebo mean 4.62 (SD 1.49); P < 0.005) and anxiety (midazolam mean 1.52 (SD 0.3); placebo mean 3.97 (SD 0.44); P < 0.0001) in one trial with 99 participants. Two other trials did not find a difference in numerical rating of anxiety (mean 1.7 (SD 2.4) for 20 participants randomized to midazolam; mean 2.6 (SD 2.9) for 22 participants randomized to placebo; P = 0.216; mean Spielberger's Trait Anxiety Inventory score 47.56 (SD 11.68) in the midazolam group; mean 52.78 (SD 9.61) in placebo group; P > 0.05). Intranasal midazolam versus placebo (2 trials; 149 participants)Midazolam induced sedation (midazolam mean 3.15 (SD 0.36); placebo mean 2.56 (SD 0.64); P < 0.001) and reduced the numerical rating of anxiety in one trial with 54 participants (midazolam mean 17.3 (SD 18.58); placebo mean 49.3 (SD 29.46); P < 0.001). There was no difference in meta-analysis of results from both trials for risk of incomplete procedures (RR 0.14, 95% CI 0.02 to 1.12; downgraded to low-quality evidence). AUTHORS' CONCLUSIONS: We found no high-quality evidence to determine if midazolam, when administered as the sole sedative agent prior to a procedure, produces more or less effective sedation than placebo or other medications. There is low-quality evidence that intravenous midazolam reduced anxiety when compared with placebo. There is inconsistent evidence that oral midazolam decreased anxiety during procedures compared with placebo. Intranasal midazolam did not reduce the risk of incomplete procedures, although anxiolysis and sedation were observed. There is moderate-quality evidence suggesting that oral midazolam produces less effective sedation than chloral hydrate for completion of procedures for children undergoing non-invasive diagnostic procedures.

Patient-controlled intranasal fentanyl analgesia: a pilot study to assess practicality and tolerability during childbirth

Background: Intranasal administration of fentanyl is a non-invasive method of analgesic delivery which has been shown to be effective. This pilot study aimed to assess the practicality and tolerability of patient-controlled intranasal fentanyl for relieving pain during childbirth. Methods: This prospective, non-randomised, clinical trial recruited women with a singleton pregnancy during November 2009 to October 2011. Exclusion criteria included respiratory disease, gestation <37 weeks and pregnancy complications. The device administered fentanyl 54 lg per spray, incorporating a 3-min lock-out. Data collected included demographics, dose, additional analgesia, adverse events, pain relief and delivery outcomes. Follow-up data were obtained within 48 h regarding tolerability of the device. Results: The final sample included 32 women: mean age was 28.7 years and gestation 39.8 weeks. Mean fentanyl dose was 734 lg and duration of use was 3.5 h. Most women (78.2%) reported satisfactory to excellent pain relief using the nasal device. Four neonates (12.5%) required bag-mask ventilation at birth: three had adequate respiration within 5 min and one required short-term observation in the special-care nursery. For all items, there was a trend towards an adverse outcome, including neonatal respiratory support, as the dose of fentanyl increased. On follow-up, 84.4% reported they would use intranasal fentanyl for their next childbirth experience. Conclusions: Patient-controlled intranasal fentanyl provides an acceptable level of analgesia during childbirth. It may, however, increase the risk of neonatal respiratory depression. Future, randomised studies should evaluate the safety and efficacy of patient-controlled intranasal fentanyl compared with existing analgesia options.