Daytime melatonin and light independently affect human alertness and body temperature

Light significantly improves alertness during the night (Cajochen, Sleep Med Rev, 11, 2007 and 453; Ruger et al., AJP Regul Integr Comp Physiol, 290, 2005 and R1413), but results are less conclusive at daytime (Lok et al., J Biol Rhythms, 33, 2018 and 589). Melatonin and core body temperature levels at those times of day may contribute to differences in alerting effects of light. In this experiment, the combined effect of daytime exogenous melatonin administration and light intensity on alertness, body temperature, and skin temperature was studied. The goal was to assess whether (a) alerting effects of light are melatonin dependent, (b) soporific effects of melatonin are mediated via the thermoregulatory system, and (c) light can improve alertness after melatonin-induced sleepiness during daytime. 10 subjects (5 females, 5 males) received melatonin (5 mg) in dim (10 lux) and, on a separate occasion, in bright polychromatic white light (2000 lux). In addition, they received placebo both under dim and bright light conditions. Subjects participated in all four conditions in a balanced order, yielding a balanced within-subject design, lasting from noon to 04:00 pm. Alertness and performance were assessed half hourly, while body temperature and skin temperature were measured continuously. Saliva samples to detect melatonin concentrations were collected half hourly. Melatonin administration increased melatonin concentrations in all subjects. Subjective sleepiness and distal skin temperature increased after melatonin ingestion. Bright light exposure after melatonin administration did not change subjective alertness scores, but body temperature and proximal skin temperature increased, while distal skin temperature decreased. Light exposure did not significantly affect these parameters in the placebo condition. These results indicate that (a) exogenous melatonin administration during daytime increases subjective sleepiness, confirming a role for melatonin in sleepiness regulation, (b) bright light exposure after melatonin ingestion significantly affected thermoregulatory parameters without altering subjective sleepiness, therefore temperature changes seem nonessential for melatonin-induced sleepiness, (c) subjective sleepiness was increased by melatonin ingestion, but bright light administration was not able to improve melatonin-induced sleepiness feelings nor performance. Other (physiological) factors may therefore contribute to differences in alerting effects of light during daytime and nighttime

An auditory brainstem implant for treatment of unilateral tinnitus:protocol for an interventional pilot study

INTRODUCTION: Tinnitus may have a very severe impact on the quality of life. Unfortunately, for many patients, a satisfactory treatment modality is lacking. The auditory brainstem implant (ABI) was originally indicated for hearing restoration in patients with non-functional cochlear nerves, for example, in neurofibromatosis type II. In analogy to a cochlear implant (CI), it has been demonstrated that an ABI may reduce tinnitus as a beneficial side effect. For tinnitus treatment, an ABI may have an advantage over a CI, as cochlear implantation can harm inner ear structures due to its invasiveness, while an ABI is presumed to not damage anatomical structures. This is the first study to implant an ABI to investigate its effect on intractable tinnitus. METHODS AND ANALYSIS: In this pilot study, 10 adults having incapacitating unilateral intractable tinnitus and ipsilateral severe hearing loss will have an ABI implanted. The ABI is switched on 6 weeks after implantation, followed by several fitting sessions aimed at finding an optimal stimulation strategy. The primary outcome will be the change in Tinnitus Functioning Index. Secondary outcomes will be tinnitus burden and quality of life (using Tinnitus Handicap Inventory and Hospital Anxiety and Depression Scale questionnaires), tinnitus characteristics (using Visual Analogue Scale, a tinnitus analysis), safety, audiometric and vestibular function. The end point is set at 1 year after implantation. Follow-up will continue until 5 years after implantation. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Institutional Review Board of the University Medical Centre Groningen, The Netherlands (METc 2015/479). The trial is registered at www.clinicialtrials.gov and will be updated if amendments are made. Results of this study will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: NCT02630589. TRIAL STATUS: Inclusion of first patient in November 2017. Data collection is in progress. Trial is open for further inclusion. The trial ends at 5 years after inclusion of the last patient

The impact of changes in taste, smell, and eating behavior in children with cancer undergoing chemotherapy:A qualitative study

Background and aims: Taste changes are the third most common bothersome symptom during treatment in children with cancer. However, it is still unclear what the essence of these taste changes are, to what degree concomitant changes in sense of smell qualify this bothersome treatment symptom and how much of an impact these changes have on the life of children with cancer. The aim of this study was to explore characteristics of both taste and smell changes and to gain insight into the impact of these changes in children with cancer receiving chemotherapy. Methods: Semi-structured interviews were performed until data saturation was achieved in each age group (6–12, 13–17 years). This resulted in an in-depth description of taste and smell changes, including its impact on the life of 27 children with various cancer types receiving chemotherapy. Thematic analysis of interview data was performed. Results: Interview data could be grouped into three main themes, namely changes in (1) taste, (2) smell, and (3) eating behavior. As expected, most children reported experiencing taste and smell changes just after start of treatment, but changes varied greatly between children; that is, some reported changes in intensity (increased or decreased), whereas others reported different perceptions or preferences (from sweet to savory). Taste and smell changes (regardless of direction) negatively impacted quality of life, with these changes commonly described as “disappointing” or “frustrating.” Interestingly, particular chemotherapeutic agents were frequently mentioned regarding taste and smell changes, prompting sensory-specific coping strategies. Children's eating behavior changed in terms of alterations in food liking and appetite, sometimes due to chemosensory changes, but children also mentioned specific medication or hospital food being responsible for their altered eating behavior. Conclusions: Both taste and smell changes are common in children with cancer. The essence of these changes varies widely, but taste and smell changes are generally considered bothersome treatment symptoms. Ways to cope with taste or smell changes specifically were described by the children warranting further research and offering the opportunity for enhancing patient-centered care

Associations between Socio-Economic Status and Unfavorable Social Indicators of Child Wellbeing; a Neighbourhood Level Data Design

Background: Living in deprivation is related to ill health. Differences in health outcomes between neighbourhoods may be attributed to neighbourhood socio-economic status (SES). Additional to differences in health, neighbourhood differences in child wellbeing could also be attributed to neighbourhood SES. Therefore, we aimed to investigate the association between neighbourhood deprivation, and social indicators of child wellbeing. Methods: Aggregated data from 3565 neighbourhoods in 390 municipalities in the Netherlands were eligible for analysis. Neighbourhood SES scores and neighbourhood data on social indicators of child wellbeing were used to perform repeated measurements, with one year measurement intervals, over a period of 11 years. Linear mixed models were used to estimate the associations between SES score and the proportion of unfavorable social indicators of child wellbeing. Results: After adjustment for year, population size, and clustering within neighbourhoods and within a municipality, neighbourhood SES was inversely associated with the proportion of ‘children living in families on welfare’ (estimates with two cubic splines: −3.59 [CI: −3.99; −3.19], and −3.00 [CI: −3.33; −2.67]), ‘delinquent youth’ (estimate −0.26 [CI: −0.30; −0.23]) and ‘unemployed youth’ (estimates with four cubic splines: −0.41 [CI: −0.57; −0.25], −0.58 [CI: −0.73; −0.43], −1.35 [−1.70; −1.01], and −0.96 [1.24; −0.70]). Conclusions: In this study using repeated measurements, a lower neighbourhood SES was significantly associated with a higher prevalence of unfavorable social indicators of child wellbeing. This contributes to the body of evidence that neighbourhood SES is strongly related to child health and a child’s ability to reach its full potential in later life. Future studies should consist of larger longitudinal datasets, potentially across countries, and should attempt to take the interpersonal variation into account with more individual-level data on SES and outcomes

Correction:Reducing growth and developmental problems in children: Development of an innovative postnatal risk assessment

[This corrects the article DOI: 10.1371/journal.pone.0217261.]

The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development

Recent loss-of-function studies in mice show that the transcription factor GATA6 is important for visceral endoderm differentiation. It is also expressed in early bronchial epithelium and the observation that this tissue does not receive any contribution from Gata6 double mutant embryonic stem (ES) cells in chimeric mice suggests that GATA6 may play a crucial role in lung development. The aim of this study was to determine the role of GATA6 in fetal pulmonary development. We show that Gata6 mRNA is expressed predominantly in the developing pulmonary endoderm and epithelium, but at E15.5 also in the pulmonary mesenchyme. Blocking or depleting GATA6 function results in diminished branching morphogenesis both in vitro and in vivo. TTF1 expression is unaltered in chimeric lungs whereas SPC and CC10 expression are attenuated in abnormally branched areas of chimeric lungs. Chimeras generated in a ROSA26 background show that endodermal cells in these abnormally branched areas are derived from Gata6 mutant ES cells, implicating that the defect is intrinsic to the endoderm. Taken together, these data demonstrate that GATA6 is not essential for endoderm specification, but is required for normal branching morphogenesis and late epithelial cell differentiation

Integrating interconception care in preventive child health care services:The Healthy Pregnancy 4 All program

BackgroundMost parents with young children pay routine visits to Well-Baby Clinics, or so-called Preventive Child Health Care (PCHC) services. This offers a unique opportunity to promote and deliver interconception care. This study aimed to integrate such care and perform an implementation evaluation.MethodsIn seven Dutch municipalities, PCHC professionals were instructed to discuss the possibility of an interconception care consultation during each routine six-months well-baby visit. The primary outcome of this study was coverage of the intervention, quantified as the proportion of visits during which women were informed about interconception care. Secondary outcomes included adoption, fidelity, feasibility, appropriateness, acceptability and effectiveness of the intervention, studied by surveying PCHC professionals and women considering becoming pregnant.ResultsThe possibility of interconception care was discussed during 29% (n = 1,849) of all visits, and 60% of the PCHC physicians adopted the promotion of interconception care by regularly informing women. About half of the PCHC professionals and most women judged integration of interconception care in PCHC appropriate and acceptable. Estimated feasibility was poor, since 13% of the professionals judged future integration in daily practice as probable. The uptake of interconception care consultations was low (n = 4 consultations).ConclusionsPromotion of interconception care was achieved in approximately one-third of the routine PCHC consultations and appeared promising with regards to adoption, appropriateness and acceptability. However, concerns on feasibility and uptake of interconception care consultations in daily practice remain. Suggestions for improvement may include further integration of interconception care health promotion in routine PCHC consultations, while allocating sufficient resources

The Relation Between Tinnitus and a Neurovascular Conflict of the Cochleovestibular Nerve on Magnetic Resonance Imaging

Introduction:Magnetic resonance (MR) imaging is often used in diagnostic evaluation of tinnitus patients. Incidental findings like a neurovascular conflict (NVC) in the cerebellopontine angle are often found; however, the diagnostic value of this finding remains unclear. The aim of this study is to investigate whether the type or degree of compression of the vestibulocochlear nerve is of diagnostic value in patients with a NVC.Methods:A retrospective study was performed in 111 tinnitus patients with available MR imaging between 2013 and 2015. Clinical and audiometric variables were gathered and MR imaging was reevaluated by two neuroradiologists. NVCs were analyzed using a grading system based on previous research by Sirikci et al.Results:In total, 220 ears were available for assessment. In patients with unilateral tinnitus a loop compression and an indentation of the cochleovestibular nerve were more frequent than in patients with bilateral tinnitus. However, there was no significant difference in distribution of the type of compression between tinnitus and nontinnitus ears. Patient with unilateral tinnitus had a significantly higher degree of hearing loss in the symptomatic ear, compared with the asymptomatic ear and with the bilateral tinnitus group. Also, it was found that the degree of hearing loss did not differ between the various types of compression.Conclusion:This study did not find a diagnostic value of specific types of compression in patients with a NVC. Although the distribution of NVC classification was different in patients with unilateral and bilateral tinnitus, there was no definite relation between the type of NVC and the presence of ipsilateral tinnitus. Also, the degree of hearing loss was not related to specific types of NVC

Decreased CXCR1 and CXCR2 expression on neutrophils in anti-neutrophil cytoplasmic autoantibody-associated vasculitides potentially increases neutrophil adhesion and impairs migration

Introduction: In anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV), persistent inflammation within the vessel wall suggests perturbed neutrophil trafficking leading to accumulation of activated neutrophils in the microvascular compartment. CXCR1 and CXCR2, being major chemokine receptors on neutrophils, are largely responsible for neutrophil recruitment. We speculate that down-regulated expression of CXCR1/2 retains neutrophils within the vessel wall and, consequently, leads to vessel damage.Methods: Membrane expression of CXCR1/2 on neutrophils was assessed by flow cytometry. Serum levels of interleukin-8 (IL-8), tumor necrosis factor alpha (TNF-α), angiopoietin 1 and angiopoietin 2 from quiescent and active AAV patients and healthy controls (HC) were quantified by ELISA. Adhesion and transendothelial migration of isolated neutrophils were analyzed using adhesion assays and Transwell systems, respectively.Results: Expression of CXCR1 and CXCR2 on neutrophils was significantly decreased in AAV patients compared to HC. Levels of IL-8, which, as TNFα, dose-dependently down-regulated CXCR1 and CXCR2 expression on neutrophils in vitro, were significantly increased in the serum of patients with active AAV and correlated negatively with CXCR1/CXCR2 expression on neutrophils, even in quiescent patients. Blocking CXCR1 and CXCR2 with repertaxin increased neutrophil adhesion and inhibited migration through a glomerular endothelial cell layer.Conclusions: Expression of CXCR1 and CXCR2 is decreased in AAV, potentially induced by circulating proinflammatory cytokines such as IL-8. Down-regulation of these chemokine receptors could increase neutrophil adhesion and impair its migration through the glomerular endothelium, contributing to neutrophil accumulation and, in concert with ANCA, persistent inflammation within the vessel wall. © 2012 Hu et al.; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Consumption of nitrate-rich beetroot juice with or without vitamin C supplementation increases the excretion of urinary nitrate, nitrate, and N-nitroso compounds in humans

Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N-nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N-nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete’s health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances