444 research outputs found

    Pulmonary Effects of Indoor- and Outdoor-Generated Particles in Children with Asthma

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    Most particulate matter (PM) health effects studies use outdoor (ambient) PM as a surrogate for personal exposure. However, people spend most of their time indoors exposed to a combination of indoor-generated particles and ambient particles that have infiltrated. Thus, it is important to investigate the differential health effects of indoor- and ambient-generated particles. We combined our recently adapted recursive model and a predictive model for estimating infiltration efficiency to separate personal exposure (E) to PM(2.5) (PM with aerodynamic diameter ā‰¤2.5 Ī¼m) into its indoor-generated (E(ig)) and ambient-generated (E(ag)) components for 19 children with asthma. We then compared E(ig) and E(ag) to changes in exhaled nitric oxide (eNO), a marker of airway inflammation. Based on the recursive model with a sample size of eight children, E(ag) was marginally associated with increases in eNO [5.6 ppb per 10-Ī¼g/m(3) increase in PM(2.5); 95% confidence interval (CI), āˆ’0.6 to 11.9; p = 0.08]. E(ig) was not associated with eNO (āˆ’0.19 ppb change per 10Ī¼g/m(3)). Our predictive model allowed us to estimate E(ag) and E(ig) for all 19 children. For those combined estimates, only E(ag) was significantly associated with an increase in eNO (E(ag): 5.0 ppb per 10-Ī¼g/m(3) increase in PM(2.5;) 95% CI, 0.3 to 9.7; p = 0.04; E(ig): 3.3 ppb per 10-Ī¼g/m(3) increase in PM(2.5); 95% CI, āˆ’1.1 to 7.7; p = 0.15). Effects were seen only in children who were not using corticosteroid therapy. We conclude that the ambient-generated component of PM(2.5) exposure is consistently associated with increases in eNO and the indoor-generated component is less strongly associated with eNO

    TRIO gene segregation in a family with cerebellar ataxia

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    Aim of the study: To report a family with a novel TRIO gene mutation associated withphenotype of cerebellar ataxia. Materials and methods: Seven family members of Caribbean descent were recruited through our ataxia research protocol; of the family members, the mother and all 3 children were found to be affected with severe young-onset and rapidly progressive truncal and appendicular ataxia leading to early disability. Array comparative genomic hybridization, mitochondrial DNA analysis, and whole-exome sequencing were performed on 3 of the family members (mother and 2 daughters). Results: While the maternal grandmother, great uncle and great aunt were unaffected, the mother and 3 children displayed cognitive dysfunction, severe ataxia, spasticity, and speech disturbances. Age of onset ranged between 3 and 17 years, with average current disease duration of 21 years. Whole-exome sequencing showed a variant p.A1214V in exon 22 of the TRIO gene in 3 of the family members. Array comparative genomic hybridization and mitochondrial DNA analysis were normal. The same variant was later discovered in all but one family member. Conclusions and clinical implications: The TRIO p.A1214V variant is associated with cerebellar ataxia in the studied family; it was present in all affected and unaffected family members. Phenotype is severe and broad. Anticipation seems to be present (based on 2 affected generations). It is warranted to screen additional familial early-onset and rapidly progressive ataxia cases for this genotype. TRIO gene mutations may well represent a novel spinocerebellar ataxia subtype

    Dutch translation and cross-cultural validation of the Adult Social Care Outcomes Toolkit (ASCOT)

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    Background: The Adult Social Care Outcomes Toolkit was developed to measure outcomes of social care in England. In this study, we translated the four level self-completion version (SCT-4) of the ASCOT for use in the Netherlands and performed a cross-cultural validation. Methods: The ASCOT SCT-4 was translated into Dutch following international guidelines, including two forward and back translations. The resulting version was pilot tested among frail older adults using think-aloud interviews. Furthermore, using a subsample of the Dutch ACT-study, we investigated test-retest reliability and construct validity and compared response distributions with data from a comparable English study. Results: The pilot tests showed that translated items were in general understood as intended, that most items were reliable, and that the response distributions of the Dutch translation and associations with other measures were comparable to the original English version. Based on the results of the pilot tests, some small modifications and a revision of the Dignity items were proposed for the final translation, which were approved by the ASCOT development team. The complete original English version and the final Dutch translation can be obtained after registration on the ASCOT website (http://www.pssru.ac.uk/ascot). Conclusions: This study provides preliminary evidence that the Dutch translation of the ASCOT is valid, reliable and comparable to the original English version. We recommend further research to confirm the validity of the modified Dutch ASCOT translation

    Blood levels of lead and dental caries in permanent teeth

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    ObjectivesThe purpose of this study was to determine whether there is an association between lead exposure within the ages of 1- 4- years and dental caries in the permanent dentition between ages 9- 17 among Mexican youth.MethodsData were collected for the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort from a group of 490 children born and reared in Mexico City. Among ages 1- 4- years, blood lead levels were measured in micrograms of lead per deciliter of blood (ƎĀ¼g/dL) and the presence of caries in adolescence was determined using the International Caries and Detection and Assessment System (ICDAS). The relationship between blood levels of lead and decayed, missing, or filled surfaces (DMFS) was examined using negative binomial regression. Covariates were selected based on previous studies and included age, gender, socioeconomic status, oral hygiene, body mass index, and diet. The nonlinear relationship between lead and DMFS was examined using smoothing splines.ResultsThe mean overall blood lead level (BLL) was 4.83- ƎĀ¼g/dL (S.D. of 2.2). The mean overall caries level (DMFS) was 4.1. No statistically significant association was found between early childhood blood lead levels and dental caries in adolescence.ConclusionThis study shows a lack of association between exposure to lead between the ages of 1- 4- years of age and dental caries in permanent dentition later in life. Other covariates, such as age and sugar consumption, appeared to play a more prominent role in caries development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163870/1/jphd12384.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163870/2/jphd12384_am.pd

    Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment

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    ACKNOWLEDGMENTS Schematic diagrams in Figures 2, 8 are created withBiorender.com. FUNDING We gratefully acknowledge the grant support from the Alzheimerā€™s Society (152 (PG-157); 290 (AS-PG-15b-018); 228 (AS-DTC-2014-017), 314 (AS ā€“PhD-16-006), and Alzheimerā€™s Research United Kingdom (ART-PG2010-3; ARUK-PG2013- 22; ARUK-PG2016B-6), and The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). ML and JB are funded by an Alzheimerā€™s Society Scotland Doctoral Training Programme and RS Macdonald Trust. ML was also funded by a China Scholarship Council (CSC)/University of Edinburgh scholarship.Peer reviewedPublisher PD

    Behaviourally modern humans in coastal southern Africa experienced an increasingly continental climate during the transition from Marine Isotope Stage 5 to 4

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    Unravelling evolution-by-environment interactions on the gut microbiome is particularly relevant considering the unprecedented level of human-driven disruption of the ecological and evolutionary trajectories of species. Here, we aimed to evaluate whether an evolutionary response to size-selective mortality influences the gut microbiome of medaka (Oryzias latipes), how environmental conditions interact with the genetic background of medaka on their microbiota, and the association between microbiome diversity and medaka growth-related traits. To do so, we studied two lineages of medaka with known divergence in foraging efficiency and life history raised under antagonistic size-selective regimes for 10 generations (i.e. the largest or the smallest breeders were removed to mimic fishing-like or natural mortality). In pond mesocosms, the two lineages were subjected to contrasting population density and light intensity (used as proxies of resource availability). We observed significant differences in the gut microbiome composition and richness between the two lines, and this effect was mediated by light intensity. The bacterial richness of fishing-like medaka (small-breeder line) was reduced by 34% under low-light conditions compared to high-light conditions, while it remained unchanged in natural mortality-selected medaka (large-breeder line). However, the observed changes in bacterial richness did not correlate with changes in adult growth-related traits. Given the growing evidence about the gut microbiomes importance to host health, more in-depth studies are required to fully understand the role of the microbiome in size-selected organisms and the possible ecosystem-level consequences.publishedVersio

    Predictive factors for sustained pain after (sub)acute osteoporotic vertebral fractures:Combined results from the VERTOS II and VERTOS IV trial

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    PURPOSE: Osteoporotic vertebral compression fractures are treated conservatively or in selected cases with percutaneous vertebroplasty (PV). The purpose of this retrospective analysis is to determine predictive factors for a high visual analogue scale (VAS) pain score after conservative, sham or PV and is based on previously published randomized trials. METHODS: The VERTOS II compared conservative versus PV, and VERTOS IV compared sham versus PV treatment. The conservative group received pain medication. The sham and PV group received subcutaneous lidocaine/bupivacaine. In addition, the PV group received cementation, which was simulated in the sham group. Nineteen different predictors of high (ā‰„ā€‰5) versus low (ā€‰8, long-term baseline pain, mild/severe Genant and new fractures. CONCLUSIONS: Statistically significant more patients had a high pain score at 12Ā months in the sham and conservative group when compared with the PV group. Five predictors were identified for sustained high local back pain, regardless of the received treatment. Patients with moderate fracture deformity were less likely to have high pain scores at 12 months if they received PV than if they had sham or conservative therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00270-022-03170-7

    Beta-frequency electrophysiological bursts: BOLD correlates and relationships with psychotic illness

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    AIMS: To identify the BOLD (blood oxygenation level dependent) correlates of bursts of beta frequency band electrophysiological activity, and to compare BOLD responses between healthy controls and patients with psychotic illness. The post movement beta rebound (PMBR) is a transient increase in power in the beta frequency band (13-30 Hz), recorded with methods such as electroencephalography (EEG), following the completion of a movement. PMBR size is reduced in patients with schizophrenia and inversely correlated with severity of illness. PMBR size is inversely correlated with measures of schizotypy in non-clinical groups. Therefore, beta-band activity may reflect a fundamental neural process whose disruption plays an important role in the pathophysiology of schizophrenia. Recent work has found that changes in beta power reflect changes in the probability-of-occurrence of transient bursts of beta-frequency activity. Understanding the generators of beta bursts could help unravel the pathophysiology of psychotic illness and thus identify novel treatment targets. METHOD: EEG data were recorded simultaneously with BOLD data measured with 3T functional magnetic resonance imaging (fMRI), whilst participants performed an n-back working memory task. We included seventy-eight participants ā€“ 32 patients with schizophrenia, 16 with bipolar disorder and 30 healthy controls. Beta bursts were identified in the EEG data using a thresholding method and burst timings were used as markers in an event-related fMRI design convolved with a conventional haemodynamic response function. A region of interest analysis compared beta-event-related BOLD activity between patients and controls. RESULT: Beta bursts phasically activated brain regions implicated in coding task-relevant content (specifically, regions involved in the phonological representation of letter stimuli, as well as areas representing motor responses). Further, bursts were associated with suppression of tonically-active regions. In the EEG, PMBR was greater in controls than patients, and, in patients, PMBR size was positively correlated with Global Assessment of Functioning scores, and negatively correlated with persisting symptoms of disorganisation and performance on a digit symbol substition test. Despite this, patients showed greater, more extensive, burst-related BOLD activation than controls. CONCLUSION: Our findings are consistent with a recent model in which beta bursts serve to reactivate latently-maintained, task-relevant, sensorimotor information. The increased BOLD response associated with bursts in patients, despite reduced PMBR, could reflect inefficiency of burst-mediated cortical synchrony, or it may suggest that the sensorimotor information reactivated by beta bursts is less precisely specified in psychosis. We propose that dysfunction of the mechanisms by which beta bursts reactivate task-relevant content can manifest as disorganisation and working memory deficits, and may contribute to persisting symptoms and impairment in psychosis
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