Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: −0.4, −0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.

Caught in the eye of the storm: a qualitative study of views and experiences of planned drug holidays from methylphenidate in child and adolescent ADHD treatment

Background: Attention deficit hyperactivity disorder (ADHD) can be treated with stimulant medication such as methylphenidate. Although effective, methylphenidate can cause serious side-effects, including suppressed appetite, growth retardation and sleep problems. A drug holiday is a deliberate interruption of pharmacotherapy for a defined period of time and for a specific clinical purpose, for example for appeasing side-effects. Whilst some international guidelines recommend introducing drug holidays in ADHD treatment, this is not practised routinely. Our aim was to examine the views and experiences of planned drug holidays from methylphenidate with adults who have responsibility for treatment decisions in children and adolescents with ADHD. Method: In-depth interviews were carried out. Child and Adolescent Mental Health Services (CAMHS) practitioners (n=8), General Practitioners (n=8), teachers (n=5), and mothers of children with ADHD (n=4) were interviewed in a UK setting. Interview transcripts were analysed using grounded theory. Results: Methylphenidate eases the experience of the child amid problems at home and at school and once started is mostly continued long-term. Some families do practise short-term drug holidays at weekends and longer-term ones during school holidays. The decision to introduce drug holidays is influenced by the child’s academic progress, the parents’ ability to cope with the child, as well as medication beliefs. Trialling a drug holiday is thought to allow older children to self-assess their ability to manage without medication when they show signs of wanting to discontinue treatment prematurely. Conclusions: Planned drug holidays could address premature treatment cessation by enabling adolescents to assess repercussions under medical supervision.

A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders

Background: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to Cognitive Behavioural Therapy (CBT) in children with anxiety disorders. Methods: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1026 monozygotic (MZ) twin pairs was examined as a function of the pairs’ genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. Results: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9%, 55.5% and 41.6% respectively). Conclusions: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments, but also benefit more from the most intensive types of treatment.

Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial

There is much speculation with regard to the potential cardioprotective benefits of equol, a microbial-derived metabolite of the isoflavone daidzein, which is produced in the large intestine after soy intake in 30% of Western populations. Although cross-sectional and retrospective data support favorable associations between the equol producer (EP) phenotype and cardiometabolic health, few studies have prospectively recruited EPs to confirm this association. The aim was to determine whether the acute vascular benefits of isoflavones differ according to EP phenotype and subsequently investigate the effect of providing commercially produced S-(–)equol to non-EPs. We prospectively recruited male EPs and non-EPs (n = 14/ group) at moderate cardiovascular risk into a double-blind, placebocontrolled crossover study to examine the acute effects of soy isoflavones (80-mg aglycone equivalents) on arterial stiffness [carotid-femoral pulse-wave velocity (cfPWV)], blood pressure, endothelial function (measured by using the EndoPAT 2000; Itamar Medical), and nitric oxide at baseline (0 h) and 6 and 24 h after intake. In a separate assessment, non-EPs consumed 40 mg S-(–)equol with identical vascular measurements performed 2 h after intake. After soy intake, cfPWV significantly improved in EPs at 24 h (cfPWV change from 0 h: isoflavone, 20.2 6 0.2 m/s; placebo, 0.6 6 0.2 m/s; P , 0.01), which was significantly associated with plasma equol concentrations (R = 20.36, P = 0.01). No vascular effects were observed in EPs at 6 h or in non-EPs at any time point. Similarly, no benefit of commercially produced S-(–)equol was observed in non-EPs despite mean plasma equol concentrations reaching 3.2 mmol/L. Acute soy intake improved cfPWV in EPs, equating to an 11–12% reduced risk of cardiovascular disease if sustained. However, a single dose of commercially produced equol had no cardiovascular benefits in non-EPs. These data suggest that the EP phenotype is critical in unlocking the vascular benefits of equol in men, and long-term trials should focus on confirming the implications of EP phenotype on cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01530893. Am J Clin Nutr doi: 10.3945/ajcn.115.125690.

Dying young: a palaeopathological analysis of child health in Roman Britain

Children represent the most vulnerable members of society, and as such provide valuable insight into past lifeways. Adverse environmental conditions translate more readily into the osteological record of children, making them primary evidence for the investigation of ill-health in the past. To date, most information on growing up in Roman Britain has been based on the Classical literature, or discussed in palaeopathological studies with a regional focus, e.g. Dorset or Durnovaria. Thus, the lifestyles and everyday realities of children throughout Britannia remained largely unknown. This study sets out to fill this gap by providing the first large scale analysis of Romano-British children from town and country. The palaeopathological analysis of 1643 non-adult (0-17 years) skeletons, compiled from the literature (N=690) and primary osteological analysis (N=953), from 27 urban and rural settlements has highlighted diverse patterns in non-adult mortality and morbidity. The distribution of ages-at-death suggest that older children and adolescents migrated from country to town, possibly for commencing their working lives. True prevalence rates suggest that caries (1.8%) and enamel hypoplasia (11.4%) were more common in children from major urban towns, whereas children in the countryside displayed higher frequencies of scurvy (6.9%), cribra orbitalia (27.7%), porotic hyperostosis (6.2%) and endocranial lesions (10.9%). Social inequality in late Roman Britain may have been the driving force behind these urban-rural dichotomies. The results may point to exploitation of the peasantry on the one hand, and higher status of the urban population as a more ‘Romanised’ group on the other. Comparison with Iron Age and post-medieval non-adults also demonstrated a decline in health in the Roman period, with some levels of ill-health, particularly in the rural children, similar to those from post-medieval London. This research provides the most comprehensive study of non-adult morbidity and mortality in Roman Britain to date. It has provided new insights into Romano-British lifeways and presents suggestions for further work.

Secoiridoids delivered as olive leaf extract induce acute improvements in human vascular function and reduction of an inflammatory cytokine: a randomised, double-blind, placebo-controlled, cross-over trial

The leaves of the olive plant (Olea europaea) are rich in polyphenols, of which oleuropein and hydroxytyrosol (HT) are most characteristic. Such polyphenols have been demonstrated to favourably modify a variety of cardiovascular risk factors. The aim of the present intervention was to investigate the influence of olive leaf extract (OLE) on vascular function and inflammation in a postprandial setting and to link physiological outcomes with absorbed phenolics. A randomised, double-blind, placebo-controlled, cross-over, acute intervention trial was conducted with eighteen healthy volunteers (nine male, nine female), who consumed either OLE (51 mg oleuropein; 10mg HT), or a matched control (separated by a 4-week wash out) on a single occasion. Vascular function was measured by digital volume pulse (DVP), while blood collected at baseline, 1, 3 and 6 h was cultured for 24 h in the presence of lipopolysaccharide in order to investigate effects on cytokine production. Urine was analysed for phenolic metabolites by HPLC. DVP-stiffness index and ex vivo IL-8 production were significantly reduced (P < 0.05) after consumption of OLE compared to the control. These effects were accompanied by the excretion of several phenolic metabolites, namely HT and oleuropein derivatives, which peaked in urine after 8-24 h. The present study provides the first evidence that OLE positively modulates vascular function and IL-8 production in vivo, adding to growing evidence that olive phenolics could be beneficial for health.

The Sick Child in Early Modern England, 1580-1720

The Sick Child in Early Modern England is a powerful exploration of the treatment, perception, and experience of illness in childhood, from the late sixteenth to the early eighteenth centuries. At this time, the sickness or death of a child was a common occurrence - over a quarter of young people died before the age of fifteen - and yet this subject has received little scholarly attention. Hannah Newton takes three perspectives: first, she investigates medical understandings and treatments of children. She argues that a concept of 'children's physic' existed amongst doctors and laypeople: the young were thought to be physiologically distinct, and in need of special medicines. Secondly, she examines the family's' experience, demonstrating that parents devoted considerable time and effort to the care of their sick offspring, and experienced feelings of devastating grief upon their illnesses and deaths. Thirdly, she takes the strikingly original viewpoint of sick children themselves, offering rare and intimate insights into the emotional, spiritual, physical, and social dimensions of sickness, pain, and death. Newton asserts that children's experiences were characterised by profound ambivalence: whilst young patients were often tormented by feelings of guilt, fears of hell, and physical pain, sickness could also be emotionally and spiritually uplifting, and invited much attention and love from parents. Drawing on a wide array of printed and archival sources, The Sick Child is of vital interest to scholars working in the interconnected fields of the history of medicine, childhood, parenthood, bodies, emotion, pain, death, religion, and gender.

The dying child in seventeenth-century England

This article offers a historical perspective on an important and controversial issue within the emerging field of paediatric palliative care: the question of whether to talk to terminally ill children about their prognosis.

Terminology matters! Why difference is not incompleteness and how early child bilinguals are heritage speakers

This paper integrates research on child simultaneous bilingual (2L1) acquisition more directly into the heritage language (HL) acquisition literature. The 2L1 literature mostly focuses on development in childhood, whereas heritage speakers (HSs) are often tested at an endstate in adulthood. However, insights from child 2L1 acquisition must be considered in HL acquisition theorizing precisely because many HSs are the adult outcomes of child 2L1 acquisition. Data from 2L1 acquisition raises serious questions for the construct of incomplete acquisition, a term broadly used in HL acquisition studies to describe almost any difference HSs display from baseline controls (usually monolinguals). We offer an epistemological discussion related to incomplete acquisition, highlighting the descriptive and theoretical inaccuracy of the term. We focus our discussion on two of several possible causal factors that contribute to variable competence outcomes in adult HSs, input (e.g., Sorace, 2004; Rothman, 2007; Pascual y Cabo & Rothman, 2012) and formal instruction (e.g., Kupisch, 2013; Kupisch et al., 2014) in the HL. We conclude by offering alternative terminology for HS outcomes.

Impact of socioeconomic and clinical factors on child oral health-related quality of life (COHRQoL)

Child oral health-related quality of life (COHRQoL) has been increasingly assessed; however, few studies appraised the influence of socioeconomic status on COHRQoL in developing countries. This study assessed the relationship of COHRQoL with socioeconomic backgrounds and clinical factors. This study followed a cross-sectional design, with a multistage random sample of 792 schoolchildren aged 12 years, representative of Santa Maria, a southern city in Brazil. Participants completed the Brazilian version of the Child Perceptions Questionnaire (CPQ(11-14)), their parents or guardians answered questions on socioeconomic status, and a dental examination provided information on the prevalence of caries, dental trauma and occlusion. The assessment of association used hierarchically adjusted Poisson regression models. Higher impacts on COHRQoL were observed for children presenting with untreated dental caries (RR 1.20; 95% CI 1.07-1.35) and maxillary overjet (RR 1.19; 95% CI 1.02-1.40). Socioeconomic factors also associated with COHRQoL; poorer scores were reported by children whose mothers have not completed primary education (RR 1.30; 95% CI 1.17-1.44) and those with lower household income (RR 1.13; 95% CI 1.02-1.26). Poor socioeconomic standings and poor dental status have a negative impact on COHRQoL; reducing health inequalities may demand dental programmes and policies targeting deprived population.

Health surveys and use of maternal and child health care services in three municipalities within the Sao Paulo metropolitan area

Objectives. To describe the changes in the use of maternal and child health care services by residents of three municipalities-Embu, Itapecerica da Serra, and Taboao da Serra-in the Sao Paulo metropolitan area, 12 years after the implementation of the Unified Health System (SUS) in Brazil, and to analyze the potential of population-based health care surveys as sources of data to evaluate these changes. Methods. Two population-based, cross-sectional surveys were carried out in 1990 and 2002 in municipalities located within the Sao Paulo metropolitan area. For children under 1 year of age, the two periods were compared in terms of outpatient services utilization and hospital admission; for the mothers, the periods were compared in terms of prenatal care and deliveries. In both surveys, stratified and multiple-stage conglomerate sampling was employed, with standardization of interview questions. Results. The most important changes observed were regarding the location of services used for prenatal care, deliveries, and hospitalization of children less than 1 year of age. There was a significant increase in the use of services in the surrounding region or hometown, and decrease in the utilization of services in the city of Sao Paulo (in 1990, 80% of deliveries and almost all admissions for children less than 1 year versus 32% and 46%, respectively, in 2002). The use of primary care units and 24-hour walk-in clinics also increased. All these changes reflect care provided by public resources. In the private sector, there was a decrease in direct payments and payments through company-paid health insurance and an increase in payments through self-paid health insurance. Conclusions. The major changes observed in the second survey occurred simultaneous to the changes that resulted from the implementation of the SUS. Population-based health surveys are adequate for analyzing and comparing the utilization of health care services at different times.

The effects of lipoic acid and alpha-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial

Antioxidants probably play an important role in the etiology of type 2 diabetes (DM2). This study evaluated the effects of supplementation with lipoic acid (LA) and alpha-tocopherol on the lipid profile and insulin sensitivity of DM2 patients. A randomized, double-blind, placebo-controlled trial involving 102 DM2 patients divided into four groups to receive daily supplementation for 4 months with: 600 mg LA (n = 26); 800 mg alpha-tocopherol (n = 25); 800 mg alpha-tocopherol + 600 mg LA (n = 25); placebo (n = 26). Plasma alpha-tocopherol, lipid profile, glucose, insulin, and the HOMA index were determined before and after supplementation. Differences within and between groups were compared by ANOVA using Bonferroni correction. Student`s t-test was used to compare means of two independent variables. The vitamin E/total cholesterol ratio improved significantly in patients supplemented with vitamin E + LA and vitamin E alone (p <= 0.001). There were improvements of the lipid fractions in the groups receiving LA and vitamin E alone or in combination, and on the HOMA index in the LA group, but not significant. The results suggest that LA and vitamin E supplementation alone or in combination did not affect the lipid profile or insulin sensitivity of DM2 patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Recent Trends in Maternal, Newborn, and Child Health in Brazil: Progress Toward Millennium Development Goals 4 and 5

We analyzed Brazil`s efforts in reducing child mortality, improving maternal and child health, and reducing socioeconomic and regional inequalities from 1990 through 2007. We compiled and reanalyzed data from several sources, including vital statistics and population-based surveys. We also explored the roles of broad socioeconomic and demographic changes and the introduction of health sector and other reform measures in explaining the improvements observed. Our findings provide compelling evidence that pro-active measures to reduce health disparities accompanied by socioeconomic progress can result in measurable improvements in the health of children and mothers in a relatively short interval. Our analysis of Brazil`s successes and remaining challenges to reach and surpass Millennium Development Goals 4 and 5 can provide important lessons for other low- and middle-income countries. (Am J Public Health. 2010;100:1877-1889. doi:10.2105/AJPH.2010.196816)