Exposure to traffic pollution, acute inflammation and autonomic response in a panel of car commuters

Background Exposure to traffic pollution has been linked to numerous adverse health endpoints. Despite this, limited data examining traffic exposures during realistic commutes and acute response exists. Objectives: We conducted the Atlanta Commuters Exposures (ACE-1) Study, an extensive panel-based exposure and health study, to measure chemically-resolved in-vehicle exposures and corresponding changes in acute oxidative stress, lipid peroxidation, pulmonary and systemic inflammation and autonomic response. Methods We recruited 42 adults (21 with and 21 without asthma) to conduct two 2-h scripted highway commutes during morning rush hour in the metropolitan Atlanta area. A suite of in-vehicle particulate components were measured in the subjects’ private vehicles. Biomarker measurements were conducted before, during, and immediately after the commutes and in 3 hourly intervals after commutes. Results At measurement time points within 3 h after the commute, we observed mild to pronounced elevations relative to baseline in exhaled nitric oxide, C-reactive-protein, and exhaled malondialdehyde, indicative of pulmonary and systemic inflammation and oxidative stress initiation, as well as decreases relative to baseline levels in the time-domain heart-rate variability parameters, SDNN and rMSSD, indicative of autonomic dysfunction. We did not observe any detectable changes in lung function measurements (FEV1, FVC), the frequency-domain heart-rate variability parameter or other systemic biomarkers of vascular injury. Water soluble organic carbon was associated with changes in eNO at all post-commute time-points (p \u3c 0.0001). Conclusions Our results point to measureable changes in pulmonary and autonomic biomarkers following a scripted 2-h highway commute

Factors Affecting the Association between Ambient Concentrations and Personal Exposures to Particles and Gases

Results from air pollution exposure assessment studies suggest that ambient fine particles [particulate matter with aerodynamic diameter ≤ 2.5 μg (PM(2.5))], but not ambient gases, are strong proxies of corresponding personal exposures. For particles, the strength of the personal–ambient association can differ by particle component and level of home ventilation. For gases, however, such as ozone (O(3)), nitrogen dioxide (NO(2)), and sulfur dioxide (SO(2)), the impact of home ventilation on personal–ambient associations is untested. We measured 24-hr personal exposures and corresponding ambient concentrations to PM(2.5), sulfate (SO(4)(2−)), elemental carbon, O(3), NO(2), and SO(2) for 10 nonsmoking older adults in Steubenville, Ohio. We found strong associations between ambient particle concentrations and corresponding personal exposures. In contrast, although significant, most associations between ambient gases and their corresponding exposures had low slopes and R(2) values; the personal–ambient NO(2) association in the fall season was moderate. For both particles and gases, personal–ambient associations were highest for individuals spending most of their time in high- compared with low-ventilated environments. Cross-pollutant models indicated that ambient particle concentrations were much better surrogates for exposure to particles than to gases. With the exception of ambient NO(2) in the fall, which showed moderate associations with personal exposures, ambient gases were poor proxies for both gas and particle exposures. In combination, our results suggest that a) ventilation may be an important modifier of the magnitude of effect in time-series health studies, and b) results from time-series health studies based on 24-hr ambient concentrations are more readily interpretable for particles than for gases

Molecular cytogenetic analysis of patients with holoprosencephaly and structural rearrangements of 7q

The holoprosencephaly (HPE) sequence is a malformation complex with abnormal midline cleavage of the embryonic forebrain. HPE is genetically heterogeneous with at least 6 different chromosome regions containing genes involved in the expression of the phenotype. HPE3, recently identified as the human Sonic hedgehog gene, is localized to 7q36. We have used fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) amplification in 5 cell lines from patients with HPE (3 cases), HPE and sacral agenesis (1 case), and microcephaly (1 case) to further define the structural rearrangements of the long arm of chromosome 7 in each case. All cell lines demonstrated loss of material in the critical region of HPE3 at band 7q36, which includes the Sonic hedgehog gene. We report here the analysis of these patient cell lines

Timing of birth for women with a twin pregnancy at term: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time.</p> <p>The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications.</p> <p>Methods/Design</p> <p>Design: Multicentred randomised trial.</p> <p>Inclusion Criteria: women with a twin pregnancy at 36⁶weeks or more without contraindication to continuation of pregnancy.</p> <p>Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36⁺⁶weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care.</p> <p>Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible).</p> <p>Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity.</p> <p>Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power).</p> <p>Discussion</p> <p>This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation.</p> <p>Clinical Trial Registration</p> <p>Current Controlled Trials ISRCTN15761056</p

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial

Objective: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. Methods: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. Results: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa&nbsp;=.65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. Significance: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype–phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype–phenotype diagnosis in the near future

Mitochondrial ATP synthase inhibition and nitric oxide are involved in muscle weakness that occurs in acute exposure of rats to monocrotophos

Organophosphate poisoning in the context of self-harm is a common medical emergency in Asia. Prolonged muscle weakness is an important but poorly understood cause of morbidity and mortality of the poisoning. This study examined mitochondrial function and its modulation by nitric oxide in muscle weakness of rats exposed to an acute, oral (0.8LD50) dose of monocrotophos. Muscle mitochondrial ATP synthase activity was inhibited in the rat in acute exposure to monocrotophos while respiration per se was not affected. This was accompanied by decreased mitochondrial uptake of calcium and increased levels of nitric oxide. Reactive cysteine groups of ATP synthase subunits were reduced in number, which may contribute to decreased enzyme activity. The decrease in ATP synthase activity and reactive cysteine groups of ATP synthase subunits was prevented by treatment of animals with the nitric oxide synthase inhibitor, L-NG Nitroarginine methyl ester, at 12 mg/kg body weight for 9 days in drinking water, prior to monocrotophos exposure. This indicated a role for nitric oxide in the process. The alterations in mitochondrial calcium uptake may influence cytosolic calcium levels and contribute to muscle weakness of acute organophosphate exposure

Perceived annoyance and asthmatic symptoms in relation to vehicle exhaust levels outside home: a cross-sectional study

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Exhaust emissions from vehicles is a well known problem with both epidemiological and experimental studies showing increasing adverse health effects with elevating levels. Many of the studies concerning vehicle exhausts and health are focused on health outcomes where the proportion attributed to exhaust is low, while there is less information on early and more frequent subjective indicators of adverse effects. Methods: The primary aim of this study was to study perceived annoyance in relation to vehicle exhaust concentrations using modelled levels of nitrogen dioxide outside the home as an indicator with high spatial resolution. Almost 2800 persons in a random sample from three Swedish cities (Umea, Uppsala and Gothenburg) responded to our questionnaire. Questions were asked to determine the degree of annoyance related to vehicle exhausts and also the prevalence of irritating and asthmatic symptoms. Exposure was described for each participants home address by meteorological dispersion models with a 50 meter resolution. Results: We found a significant increase of peoples &apos; self-assessed annoyance with rising levels of NO2. The odds of being very annoyed by vehicle exhausts increased by 14 % per 1 µg/m3 increas

Toward a better definition of focal cortical dysplasia: An iterative histopathological and genetic agreement trial.

OBJECTIVE: Focal cortical dysplasia (FCD) is a major cause of difficult-to-treat epilepsy in children and young adults, and the diagnosis is currently based on microscopic review of surgical brain tissue using the International League Against Epilepsy classification scheme of 2011. We developed an iterative histopathological agreement trial with genetic testing to identify areas of diagnostic challenges in this widely used classification scheme. METHODS: Four web-based digital pathology trials were completed by 20 neuropathologists from 15 countries using a consecutive series of 196 surgical tissue blocks obtained from 22 epilepsy patients at a single center. Five independent genetic laboratories performed screening or validation sequencing of FCD-relevant genes in paired brain and blood samples from the same 22 epilepsy patients. RESULTS: Histopathology agreement based solely on hematoxylin and eosin stainings was low in Round 1, and gradually increased by adding a panel of immunostainings in Round 2 and the Delphi consensus method in Round 3. Interobserver agreement was good in Round 4 (kappa = .65), when the results of genetic tests were disclosed, namely, MTOR, AKT3, and SLC35A2 brain somatic mutations in five cases and germline mutations in DEPDC5 and NPRL3 in two cases. SIGNIFICANCE: The diagnoses of FCD 1 and 3 subtypes remained most challenging and were often difficult to differentiate from a normal homotypic or heterotypic cortical architecture. Immunohistochemistry was helpful, however, to confirm the diagnosis of FCD or no lesion. We observed a genotype-phenotype association for brain somatic mutations in SLC35A2 in two cases with mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy. Our results suggest that the current FCD classification should recognize a panel of immunohistochemical stainings for a better histopathological workup and definition of FCD subtypes. We also propose adding the level of genetic findings to obtain a comprehensive, reliable, and integrative genotype-phenotype diagnosis in the near future

Nitrogen dioxide and allergic sensitization in the 2005–2006 National Health and Nutrition Examination Survey

Allergic sensitization is a risk factor for asthma and allergic diseases. The relationship between ambient air pollution and allergic sensitization is unclear