280 research outputs found
Antioxidant responses and NRF2 in synergistic developmental toxicity of PAHs in zebrafish
Author Posting. © The Authors, 2009. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Toxicological Sciences 109 (2009): 217-227, doi:10.1093/toxsci/kfp038.Early piscine life-stages are sensitive to polycyclic aromatic hydrocarbon (PAH) exposure,
which can cause pericardial effusion and craniofacial malformations. We previously reported that
certain combinations of PAHs cause synergistic developmental toxicity, as observed with co-exposure
to the aryl hydrocarbon receptor (AHR) agonist β-naphthoflavone (BNF) and cytochrome P4501A
inhibitor α-naphthoflavone (ANF). Herein, we hypothesized that oxidative stress is a component of
this toxicity. We examined induction of antioxidant genes in zebrafish embryos (Danio rerio)
exposed to BNF or ANF individually, a BNF+ANF combination, and a pro-oxidant positive control,
tert-butylhydroperoxide (tBOOH). We measured total glutathione, and attempted to modulate
deformities using the glutathione synthesis inhibitor buthionine sulfoxamine (BSO) and increase
glutathione pools with N-acetyl cysteine (NAC). In addition, we used a morpholino to knockdown
expression of the antioxidant response element transcription factor NRF2 to determine if this would
alter gene expression or increase deformity severity. BNF+ANF co-exposure significantly increased
expressions of superoxide dismutase1 and2, glutathione peroxidase 1, pi class glutathione-s-transferase,
and glutamate cysteine-ligase to a greater extent than tBOOH, BNF, or ANF alone. BSO
pretreatment decreased some glutathione levels, but did not worsen deformities, nor did NAC
diminish toxicity. Knockdown of NRF2 increased mortality following tBOOH challenge, prevented
significant upregulation of antioxidant genes following both tBOOH and BNF+ANF exposures, and
exacerbated BNF+ANF‐related deformities. Collectively, these findings demonstrate that antioxidant
responses are a component of PAH synergistic developmental toxicity, and that NRF2 is protective
against prooxidant and PAH challenges during development.This work was supported by the National Institute for Environmental Health Sciencessupported
Duke University Superfund Basic Research Program (P42 ES10356), National Institute for
Environmental Health Sciences‐supported Duke University Integrated Toxicology & Environmental
Health Program (TS ES07031), United States Environmental Protection Agency STAR fellowship (to
A.T.‐L.), Duke University RJR‐Leon Golberg Memorial Postdoctoral Training Program in Toxicology
(to A.T.‐L.), and the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution,
with funding provided by the J. Seward Johnson Fund and The Walter A. and Hope Noyes Smith
Chair (to A.T‐L)
Size and Shape Differences Between Male and Female Foot Bones
This study introduces a new technique to measure bone size and
shape. A three-dimensional laser scan was taken of the talus, navicular,
medial cuneiform, and first metatarsal from 107 skeletons of known age
and sex. The bones were analyzed for differences in bone morphology
between the sexes and the ability of each bone to contribute to the adducted
position of the first metatarsal. Linear measurements showed
that male bones were larger than female bones. Measurements of articular
surfaces suggested that female bones had the potential for more
movement to occur in the direction of adduction, possibly resulting in
the female first metatarsal being more adducted than that in the male
skeleton. Such differences may underlie the predisposition of the female
foot to develop hallux valgus deformity
The importance of school in the management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS):issues identified by adolescents and their families
Qualitative study of the acceptability and feasibility of acceptance and commitment therapy for adolescents with chronic fatigue syndrome
BACKGROUND: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is disabling and relatively common. Although evidenced-based treatments are available, at least 15% of children remain symptomatic after one year of treatment. Acceptance and commitment therapy (ACT) is an alternative therapy option; however, little is known about whether it is an acceptable treatment approach. Our aim was to find out if adolescents who remain symptomatic with CFS/ME after 12 months of treatment would find ACT acceptable, to inform a randomised controlled trial (RCT) of ACT. METHODS: We recruited adolescents (diagnosed with CFS/ME; not recovered after one year of treatment; aged 11–17 years), their parent/carer and healthcare professionals (HCPs) from one specialist UK paediatric CFS/ME service. We conducted semi-structured interviews to explore barriers to recovery; views on current treatments; acceptability of ACT; and feasibility of an effectiveness RCT. Thematic analysis was used to identify patterns in data. RESULTS: Twelve adolescents, eleven parents and seven HCPs were interviewed. All participants thought ACT was acceptable. Participants identified reasons why ACT might be efficacious: pragmatism, acceptance and compassion are valued in chronic illness; values-focussed treatment provides motivation and direction; psychological and physical needs are addressed; normalising difficulties is a useful life-skill. Some adolescents preferred ACT to cognitive behavioural therapy as it encouraged accepting (rather than challenging) thoughts. Most adolescents would consent to an RCT of ACT but a barrier to recruitment was reluctance to randomisation. All HCPs deemed ACT feasible to deliver. Some were concerned patients might confuse ‘acceptance’ with ‘giving up’ and called for clear explanations. All participants thought the timing of ACT should be individualised. CONCLUSIONS: All adolescents with CFS/ME, parents and HCPs thought ACT was acceptable, and most adolescents were willing to try ACT. An RCT needs to solve issues around randomisation and timing of the intervention
Rapid Systematic Review: The Impact of Social Isolation and Loneliness on the Mental Health of Children and Adolescents in the Context of COVID-19
OBJECTIVE: Disease containment of COVID-19 has necessitated widespread social isolation. We aimed to establish what is known about how loneliness and disease containment measures impact on the mental health in children and adolescents. METHOD: For this rapid review, we searched MEDLINE, PSYCHINFO, and Web of Science for articles published between 01/01/1946 and 03/29/2020. 20% of articles were double screened using pre-defined criteria and 20% of data was double extracted for quality assurance. RESULTS: 83 articles (80 studies) met inclusion criteria. Of these, 63 studies reported on the impact of social isolation and loneliness on the mental health of previously healthy children and adolescents (n=51,576; mean age 15.3) 61 studies were observational; 18 were longitudinal and 43 cross sectional studies assessing self-reported loneliness in healthy children and adolescents. One of these studies was a retrospective investigation after a pandemic. Two studies evaluated interventions. Studies had a high risk of bias although longitudinal studies were of better methodological quality. Social isolation and loneliness increased the risk of depression, and possibly anxiety at the time loneliness was measured and between 0.25 to 9 years later. Duration of loneliness was more strongly correlated with mental health symptoms than intensity of loneliness. CONCLUSION: Children and adolescents are probably more likely to experience high rates of depression and probably anxiety during and after enforced isolation ends. This may increase as enforced isolation continues. Clinical services should offer preventative support and early intervention where possible and be prepared for an increase in mental health problems
Developing a virtual reality environment for petrous bone surgery: a state-of-the-art review
The increasing power of computers has led to the development of sophisticated systems that aim to immerse the user in a virtual environment. The benefits of this type of approach to the training of physicians and surgeons are immediately apparent. Unfortunately the implementation of “virtual reality” (VR) surgical simulators has been restricted by both cost and technical limitations. The few successful systems use standardized scenarios, often derived from typical clinical data, to allow the rehearsal of procedures. In reality we would choose a system that allows us not only to practice typical cases but also to enter our own patient data and use it to define the virtual environment. In effect we want to re-write the scenario every time we use the
environment and to ensure that its behavior exactly duplicates the behavior of the real tissue. If this can be achieved then VR systems can be used not only to train surgeons but also to rehearse individual procedures where variations in anatomy or pathology present specific surgical problems. The European Union has recently funded a multinational 3-year project (IERAPSI, Integrated
Environment for Rehearsal and Planning of Surgical Interventions) to produce a virtual reality
system for surgical training and for rehearsing individual procedures. Building the IERAPSI system will bring together a wide range of experts and combine the latest technologies to produce a true, patient specific virtual reality surgical simulator for petrous/temporal bone
procedures. This article presents a review of the “state of the art” technologies currently available to construct a system of this type and an overview of the functionality and specifications such a system requires
Improving regional applicability of the UK shared socioeconomic Pathways through iterative participatory co-design
Loneliness and mental health in children and adolescents with pre-existing mental health problems: A rapid systematic review
Objectives: Periods of social isolation are associated with loneliness in children and young people, and loneliness is associated with poor mental and physical health. Children and young people with pre-existing mental health difficulties may be prone to loneliness. Containment of COVID-19 has necessitated widespread social isolation, with unprecedented school closures and restrictions imposed on social interactions. This rapid review aimed to establish what is known about the relationship between loneliness and mental health problems in children and young people with pre-existing mental health problems. Methods: We sought to identify all primary research that examined the cross-sectional and longitudinal associations between loneliness/perceived social isolation and mental health in children and young people with pre-existing mental health problems. We also aimed to identify effective interventions that reduce the adverse impact of loneliness. A rapid systematic search was conducted using MEDLINE, PsycINFO, and Web of Science. Results: Of 4,531 papers screened, 15 included children and young people with pre-existing mental health conditions. These 15 studies included 1,536 children and young people aged between 6 and 23 years with social phobia, anxiety and/or depression, and neurodevelopmental disorders. Loneliness was associated with anxiety and depression both cross-sectionally and prospectively in children and young people with mental health problems and neurodevelopmental conditions. We found preliminary evidence that psychological treatments can help to reduce feelings of loneliness in this population. Conclusions: Loneliness is associated with depression and anxiety in children and young people with pre-existing mental health conditions, and this relationship may be bidirectional. Existing interventions to address loneliness and/or mental health difficulties in other contexts may be applied to this population, although they may need adaptation and testing in younger children and adolescents. Practitioner points: Loneliness is common in children and young people, and during periods of enforced social isolation such as during COVID-19, children and young people report high levels of loneliness (or increased rates of loneliness). The review showed that loneliness is associated, both cross-sectionally and prospectively, in children and young people with mental health problems and also in children and young people with neurodevelopmental conditions, such as autism spectrum disorder. Thus, loneliness is a possible risk factor of which mental health providers should be aware. Maintaining social contact both by direct and by indirect means, especially through the Internet, could be important in mitigating loneliness. Interventions to address loneliness should be further developed and tested to help children and young people with pre-existing mental health problems who are lonely by preventing exacerbation of their mental health difficulties, in particular anxiety and depression
Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.
Abstract
Introduction
Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI).
Methods
Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings.
Results
We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year.
Conclusions
In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship
The epidemiology of patellar luxation in dogs attending primary-care veterinary practices in England
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