A new electrochemical method for the determination of chondroitin sulfate based on its supramolecular interaction with cupferron-lead(II) complex

In this paper, the interaction of cupferron (Cup) and lead (II) complex [Cup-Pb (II)] with chondroitin sulfate (CS) was investigated by linear sweep voltammetric method. In the selected medium of pH 5.5 (acetic acid-hexamine buffer solution), Cup can interact with Pb (II) to form a stable complex of [Cup-Pb(II)], which has a sensitive second order derivative polarographic reductive peak at -0.64V (vs.SCE). After the addition of CS into Cup-Pb (II) complex solution, the reductive peak current decreased without any shift of the peak potential and no new peak appeared, which indicated that an unelectroactive supramolecular complex of CS with [Cup-Pb(II)] was formed. The binding reaction conditions were carefully investigated. Under the optimal conditions, the interaction mechanism was discussed. The decrease of reductive peak current was directly proportional to the CS concentration, thus a new quantitative determination method for CS was established with the linear regression equation as ΔIp″(nA)=36.97 C/mg L-1+12.45 (n=10, γ=0.995). The effects of other substances on the determination were carefully investigated and three synthetic samples were determined with satisfactory results. The binding constant (βs) and the binding number (m) of CS with [Cup-Pb(II)] complex were calculated from the voltammetric data with the results as βs=1.89×1010 and m≈2.5

Associations of sedentary behaviour, physical activity, blood pressure and anthropometric measures with cardiorespiratory fitness in children with cerebral palsy

Background - Children with cerebral palsy (CP) have poor cardiorespiratory fitness in comparison to their peers with typical development, which may be due to low levels of physical activity. Poor cardiorespiratory fitness may contribute to increased cardiometabolic risk. Purpose - The aim of this study was to determine the association between sedentary behaviour, physical activity and cardiorespiratory fitness in children with CP. An objective was to determine the association between cardiorespiratory fitness, anthropometric measures and blood pressure in children with CP. Methods- This study included 55 ambulatory children with CP [mean (SD) age 11.3 (0.2) yr, range 6-17 yr; Gross Motor Function Classification System (GMFCS) levels I and II]. Anthropometric measures (BMI, waist circumference and waist-height ratio) and blood pressure were taken. Cardiorespiratory fitness was measured using a 10 m shuttle run test. Children were classified as low, middle and high fitness according to level achieved on the test using reference curves. Physical activity was measured by accelerometry over 7 days. In addition to total activity, time in sedentary behaviour and light, moderate, vigorous, and sustained moderate-to-vigorous activity (≥10 min bouts) were calculated. Results - Multiple regression analyses revealed that vigorous activity (β = 0.339, p<0.01), sustained moderate-to-vigorous activity (β = 0.250, p<0.05) and total activity (β = 0.238, p<0.05) were associated with level achieved on the shuttle run test after adjustment for age, sex and GMFCS level. Children with high fitness spent more time in vigorous activity than children with middle fitness (p<0.05). Shuttle run test level was negatively associated with BMI (r2 = -0.451, p<0.01), waist circumference (r2 = -0.560, p<0.001), waist-height ratio (r2 = -0.560, p<0.001) and systolic blood pressure (r2 = -0.306, p<0.05) after adjustment for age, sex and GMFCS level. Conclusions - Participation in physical activity, particularly at a vigorous intensity, is associated with high cardiorespiratory fitness in children with CP. Low cardiorespiratory fitness is associated with increased cardiometabolic risk

Feasibility of multi-sector policy measures that create activity-friendly environments for children: results of a Delphi study

<p>Abstract</p> <p>Background</p> <p>Although multi-sector policy is a promising strategy to create environments that stimulate physical activity among children, little is known about the feasibility of such a multi-sector policy approach. The aims of this study were: to identify a set of tangible (multi-sector) policy measures at the local level that address environmental characteristics related to physical activity among children; and to assess the feasibility of these measures, as perceived by local policy makers.</p> <p>Methods</p> <p>In four Dutch municipalities, a Delphi study was conducted among local policy makers of different policy sectors (public health, sports, youth and education, spatial planning/public space, traffic and transportation, and safety). In the first Delphi round, respondents generated a list of possible policy measures addressing three environmental correlates of physical activity among children (social cohesion, accessibility of facilities, and traffic safety). In the second Delphi round, policy makers weighted different feasibility aspects (political feasibility, cultural/community acceptability, technical feasibility, cost feasibility, and legal feasibility) and assessed the feasibility of the policy measures derived from the first round. The third Delphi round was aimed at reaching consensus by feedback of group results. Finally, one overall feasibility score was calculated for each policy measure.</p> <p>Results</p> <p>Cultural/community acceptability, political feasibility, and cost feasibility were considered most important feasibility aspects. The Delphi studies yielded 16 feasible policy measures aimed at physical and social environmental correlates of physical activity among children. Less drastic policy measures were considered more feasible, whereas environmental policy measures were considered less feasible.</p> <p>Conclusions</p> <p>This study showed that the Delphi technique can be a useful tool in reaching consensus about feasible multi-sector policy measures. The study yielded several feasible policy measures aimed at physical and social environmental correlates of physical activity among children and can assist local policy makers in designing multi-sector policies aimed at an activity-friendly environment for children.</p

Upregulation of CRABP1 in human neuroblastoma cells overproducing the Alzheimer-typical Aβ42 reduces their differentiation potential

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is characterized by neurodegeneration and changes in cellular processes, including neurogenesis. Proteolytic processing of the amyloid precursor protein (APP) plays a central role in AD. Owing to varying APP processing, several β-amyloid peptides (Aβ) are generated. In contrast to the form with 40 amino acids (Aβ₄₀), the variant with 42 amino acids (Aβ₄₂) is thought to be the pathogenic form triggering the pathological cascade in AD. While total-Aβ effects have been studied extensively, little is known about specific genome-wide effects triggered by Aβ₄₂or Aβ₄₀derived from their direct precursor C99.</p> <p>Methods</p> <p>A combined transcriptomics/proteomics analysis was performed to measure the effects of intracellularly generated Aβ peptides in human neuroblastoma cells. Data was validated by real-time polymerase chain reaction (real-time PCR) and a functional validation was carried out using RNA interference.</p> <p>Results</p> <p>Here we studied the transcriptomic and proteomic responses to increased or decreased Aβ₄₂and Aβ₄₀levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix) and proteomic approaches were combined to analyze the cellular response to the changed Aβ₄₂- and Aβ₄₀-levels. The cells responded to this challenge with significant changes in their expression pattern. We identified several dysregulated genes and proteins, but only the cellular retinoic acid binding protein 1 (CRABP1) was up-regulated exclusively in cells expressing an increased Aβ₄₂/Aβ₄₀ratio. This consequently reduced all-trans retinoic acid (RA)-induced differentiation, validated by CRABP1 knock down, which led to recovery of the cellular response to RA treatment and cellular sprouting under physiological RA concentrations. Importantly, this effect was specific to the AD typical increase in the Aβ₄₂/Aβ₄₀ratio, whereas a decreased ratio did not result in up-regulation of CRABP1.</p> <p>Conclusion</p> <p>We conclude that increasing the Aβ₄₂/Aβ₄₀ratio up-regulates CRABP1, which in turn reduces the differentiation potential of the human neuroblastoma cell line SH-SY5Y, but increases cell proliferation. This work might contribute to the better understanding of AD neurogenesis, currently a controversial topic.</p

Factors associated with low fitness in adolescents – A mixed methods study

Background: Fitness and physical activity are important for cardiovascular and mental health but activity and fitness levels are declining especially in adolescents and among girls. This study examines clustering of factors associated with low fitness in adolescents in order to best target public health interventions for young people. Methods: 1147 children were assessed for fitness, had blood samples, anthropometric measures and all data were linked with routine electronic data to examine educational achievement, deprivation and health service usage. Factors associated with fitness were examined using logistic regression, conditional trees and data mining cluster analysis. Focus groups were conducted with children in a deprived school to examine barriers and facilitators to activity for children in a deprived community. Results: Unfit adolescents are more likely to be deprived, female, have obesity in the family and not achieve in education. There were 3 main clusters for risk of future heart disease/diabetes (high cholesterol/insulin); children at low risk (not obese, fit, achieving in education), children ‘visibly at risk’ (overweight, unfit, many hospital/GP visits) and ‘invisibly at risk’ (unfit but not overweight, failing in academic achievement). Qualitative findings show barriers to physical activity include cost, poor access to activity, lack of core physical literacy skills and limited family support. Conclusions: Low fitness in the non-obese child can reveal a hidden group who have high risk factors for heart disease and diabetes but may not be identified as they are normal weight. In deprived communities low fitness is associated with non-achievement in education but in non-deprived communities low fitness is associated with female gender. Interventions need to target deprived families and schools in deprived areas with community wide campaigns

GBR 12909 administration as a mouse model of bipolar disorder mania: mimicking quantitative assessment of manic behavior

Mania is a core feature of bipolar disorder (BD) that traditionally is assessed using rating scales. Studies using a new human behavioral pattern monitor (BPM) recently demonstrated that manic BD patients exhibit a specific profile of behavior that differs from schizophrenia and is characterized by increased motor activity, increased specific exploration, and perseverative locomotor patterns as assessed by spatial d. It was hypothesized that disrupting dopaminergic homeostasis by inhibiting dopamine transporter (DAT) function would produce a BD mania-like phenotype in mice as assessed by the mouse BPM. We compared the spontaneous locomotor and exploratory behavior of C57BL/6J mice treated with the catecholamine transporter inhibitor amphetamine or the selective DAT inhibitor GBR 12909 in the mouse BPM. We also assessed the duration of the effect of GBR 12909 by testing mice in the BPM for 3 h and its potential strain dependency by testing 129/SvJ mice. Amphetamine produced hyperactivity and increased perseverative patterns of locomotion as reflected in reduced spatial d values but reduced exploratory activity in contrast to the increased exploration observed in BD patients. GBR 12909 increased activity and reduced spatial d in combination with increased exploratory behavior, irrespective of inbred strain. These effects persisted for at least 3 h. Thus, selectively inhibiting the DAT produced a long-lasting cross-strain behavioral profile in mice that was consistent with that observed in manic BD patients. These findings support the use of selective DAT inhibition in animal models of the impaired dopaminergic homeostasis putatively involved in the pathophysiology of BD mania

The PLANES study: a protocol for a randomised controlled feasibility study of the placental growth factor (PlGF) blood test-informed care versus standard care alone for women with a small for gestational age fetus at or after 32 + 0 weeks' gestation.

BackgroundStillbirth remains a major concern across the globe and in some high-resource countries, such as the UK; efforts to reduce the rate have achieved only modest reductions. One third of stillborn babies are small for gestational age (SGA), and these pregnancies are also at risk of neonatal adverse outcomes and lifelong health problems, especially when delivered preterm. Current UK clinical guidance advocates regular monitoring and early term delivery of the SGA fetus; however, the most appropriate regimen for surveillance of these babies remains unclear and often leads to increased intervention for a large number of these women. This pilot trial will determine the feasibility of a large-scale trial refining the risk of adverse pregnancy outcome in SGA pregnancies using biomarkers of placental function sFlt-1/PlGF, identifying and intervening in only those deemed at highest risk of stillbirth.MethodsPLANES is a randomised controlled feasibility study of women with an SGA fetus that will be conducted at two tertiary care hospitals in the UK. Once identified on ultrasound, women will be randomised into two groups in a 3:1 ratio in favour of sFlt-1/PlGF ratio led management vs standard care. Women with an SGA fetus and a normal sFlt-1/PlGF ratio will have a repeat ultrasound and sFlt-1/PlGF ratio every 2 weeks with planned birth delayed until 40 weeks. In those women with an SGA fetus and an abnormal sFlt-1/PlGF ratio, we will offer birth from 37 weeks or sooner if there are other concerning features on ultrasound. Women assigned to standard care will have an sFlt-1/PlGF ratio taken, but the results will be concealed from the clinical team, and the woman's pregnancy will be managed as per the local NHS hospital policy. This integrated mixed method study will also involve a health economic analysis and a perspective work package exploring trial feasibility through interviews and questionnaires with participants, their partners, and clinicians.DiscussionOur aim is to determine feasibility through the assessment of our ability to recruit and retain participants to the study. Results from this pilot study will inform the design of a future large randomised controlled trial that will be adequately powered for adverse pregnancy outcome. Such a study would provide the evidence needed to guide future management of the SGA fetus.Trial registrationISRCTN58254381 . Registered on 4 July 2019

Maternal plasma levels of oxytocin during physiological childbirth - a systematic review with implications for uterine contractions and central actions of oxytocin

Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levels of oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in the included studies. An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, and PsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n = 4039), 69 articles were examined in full-text and 20 papers met inclusion criteria. As the articles differed in design and methodology used for analysis of oxytocin levels, a narrative synthesis was created and the material was categorised according to effects. Basal levels of oxytocin increased 3-4-fold during pregnancy. Pulses of oxytocin occurred with increasing frequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 min towards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred in the third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in time with individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levels were also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well as into the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum. Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels in physiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin. Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages of labour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin in the circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiology and behaviour during birth. Oxytocin given as an infusion does not cross into the mother's brain because of the blood brain barrier and does not influence brain function in the same way as oxytocin during normal labour does