Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

This chapter will introduce the reader to the pathophysiology of two devastating neurologic events, traumatic brain injury (TBI) and acute ischemic stroke (AIS). Here we focus on the role of key pro-inflammatory and anti-inflammatory cytokines. Several experimental interventions have been found to modulate cytokine production and brain injury after AIS or TBI. Here minocycline, biological response modifiers, hormonal therapies, omega-3 fatty acids, N-acetylcysteine, and cannabinoids will be discussed. In addition, the role of cytokine-induced inflammasomes in both TBI and AIS will be addressed and followed by discussion of pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-18, and IFN-γ). Finally, the main anti-inflammatory cytokines, IL-33, IL-10, IL-6, and IL-4, will be discussed in the context of both TBI and AIS. It should be noted that the role of these cytokines is diverse and the dichotomization of classically pro-versus anti-inflammatory cytokines is being re-examined, as many of these cytokines have been found to play dual roles in TBI and AIS brain injury

The physical activity experiences of men with serious mental illness: Three short stories

Objectives: Although a considerable amount of research has explored the effects of physical activity on mental health, the voices of people with mental illness have been largely excluded from published reports. Through this study we aim to foreground service users' voices in order to shed light on the personal and subjective nature of the relationship between physical activity and serious mental illness (SMI). Methods: An interpretive case study approach was used to explore in depth the physical activity experiences of three men with SMI. Creative analytic practice was used to write three creative non-fictions which, as first-person narratives, foreground the participants' voices. Results: We present three short stories in an effort to communicate participants' personal and subjective experiences of physical activity in an accessible, engaging, and evocative manner. We hope to: (i) provide potentially motivating physical activity success stories for others who live with SMI; (ii) increase awareness among mental health professionals of the possibilities of physical activity; and (iii) provide an empathetic understanding of possibilities and problems of living with SMI which may help challenge the stigma surrounding mental illness. Conclusions: For us, the stories communicate the diversity and difference inherent in the ways men with SMI experience physical activity. We reflect on how the short story form allows these differences to be preserved and respected. We resist making further interpretations of the stories preferring instead to encourage the reader to form her or his own conclusions. © 2007 Elsevier Ltd. All rights reserved

Relationship of age, gender, race, and body size to infrarenal aortic diameter

AbstractPurpose: To assess the effects of age, gender, race, and body size on infrarenal aortic diameter (IAD) and to determine expected values for IAD on the basis of these factors.Methods: Veterans aged 50 to 79 years at 15 Department of Veterans Affairs medical centers were invited to undergo ultrasound measurement of IAD and complete a prescreening questionnaire. We report here on 69,905 subjects who had no previous history of abdominal aortic aneurysm (AAA) and no ultrasound evidence of AAA (defined as IAD ≥ 3.0 cm).Results: Although age, gender, black race, height, weight, body mass index, and body surface area were associated with IAD by multivariate linear regression (all p < 0.001), the effects were small. Female sex was associated with a 0.14 cm reduction in IAD and black race with a 0.01 cm increase in IAD. A 0.1 cm change in IAD was associated with large changes in the independent variables: 29 years in age, 19 cm or 40 cm in height, 35 kg in weight, 11 kg/m2 in body mass index, and 0.35 m2 in body surface area. Nearly all height-weight groups were within 0.1 cm of the gender means, and the unadjusted gender means differed by only 0.23 cm. The variation among medical centers had more influence on IAD than did the combination of age, gender, race, and body size.Conclusions: Age, gender, race, and body size have statistically significant but small effects on IAD. Use of these parameters to define AAA may not offer sufficient advantage over simpler definitions (such as an IAD ≥3.0 cm) to be warranted. (J Vasc Surg 1997;26:595-601.

Expanding the horizon of research into the pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition

White matter pathologies are critically involved in the etiology of vascular cognitive impairment–dementia (VCID), Alzheimer’s disease (AD), and Alzheimer’s disease and related diseases (ADRD), and therefore need to be considered a treatable target (Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793–4, [1]. To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of “The Albert Research Institute for White Matter and Cognition” in 2020. The first annual “Institute” meeting was held virtually on March 3–4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust–sponsored workshops (Barone et al. in J Transl Med 14:1–14, [2]; Sorond et al. in GeroScience 42:81–96, [3]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop

Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins

Bioinorganic canon states that active-site thiolate coordination promotes rapid electron transfer (ET) to and from type 1 copper proteins. In recent work, we have found that copper ET sites in proteins also can be constructed without thiolate ligation (called “type zero” sites). Here we report multifrequency electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopic data together with density functional theory (DFT) and spectroscopy-oriented configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1 centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding

The angiotensin type 1 receptor antagonist, eprosartan, attenuates the progression of renal disease in spontaneously hypertensive stroke-prone rats with accelerated hypertension

ABSTRACT The effects of the angiotensin type 1 (AT 1 ) receptor antagonist, eprosartan, were studied in a model of severe, chronic hypertension. Treatment of male spontaneously hypertensive stroke prone rats (SHR-SP) fed a high-fat, high-salt diet with eprosartan (60 mg/kg/day i.p.) for 12 weeks resulted in a lowering of blood pressure (250 Ϯ 9 versus 284 Ϯ 8 mm Hg), renal expression of transforming growth factor-␤ mRNA (1.5 Ϯ 0.2 versus 5.4 Ϯ 1.4) and the matrix components: plasminogen activator inhibitor-1 (5.2 Ϯ 1.4 versus 31.4 Ϯ 10.7), fibronectin (2.2 Ϯ 0.6 versus 8.2 Ϯ 2.2), collagen I-␣1 (5.6 Ϯ 2.0 versus 23.8 Ϯ 7.3), and collagen III (2.7 Ϯ 0.9 versus 7.6 Ϯ 2.1). Data were corrected for rpL32 mRNA expression and expressed relative to Wistar Kyoto (WKY) rats [ϭ1.0]. Expression of fibronectin protein was also lowered by eprosartan (0.8 Ϯ 0.1 versus 1.9 Ϯ 0.5), relative to WKY rats. Eprosartan provided significant renoprotection to SHR-SP rats as measured by decreased proteinuria (22 Ϯ 2 versus 127 Ϯ 13 mg/day) and histological evidence of active renal damage (5 Ϯ 2 versus 195 Ϯ 6) and renal fibrosis (5.9 Ϯ 0.7 versus 16.4 Ϯ 1.9) in vehicle-versus eprosartantreated rats, respectively. Our results demonstrated that AT 1 receptor blockade with eprosartan can reduce blood pressure and preserve renal structure and function in this model of severe, chronic hypertension. These effects were accompanied by a decreased renal expression of transforming growth factor-␤1, plasminogen activator inhibitor-1, and several other extracellular matrix proteins compared with vehicle-treated SHR-SP. The renin-angiotensin system is a major regulator of blood pressure within the body, through the maintenance of vascular tone and sodium homeostasis. The renin-angiotensin system has, however, also been implicated in a number of diseases, characterized by remodeling and fibrosis, including forms of progressive renal disease. The generation of angiotensin II can lead to organ damage through both mitogenic activity and profibrotic remodeling. Eprosartan is a potent (K i ϭ 1.4 nM) angiotensin II receptor antagonist selective for the AT 1 subtype. AT 1 receptor antagonists have been shown to attenuate the effects of exogenous angiotensin II Materials and Methods Experimental Design. Male SHR-SP rats, progeny from the strain developed b

Long-Term Exposure to Primary Traffic Pollutants and Lung Function in Children: Cross-Sectional Study and Meta-Analysis.

BACKGROUND: There is widespread concern about the possible health effects of traffic-related air pollution. Nitrogen dioxide (NO2) is a convenient marker of primary pollution. We investigated the associations between lung function and current residential exposure to a range of air pollutants (particularly NO2, NO, NOx and particulate matter) in London children. Moreover, we placed the results for NO2 in context with a meta-analysis of published estimates of the association. METHODS AND FINDINGS: Associations between primary traffic pollutants and lung function were investigated in 4884 children aged 9-10 years who participated in the Child Heart and Health Study in England (CHASE). A systematic literature search identified 13 studies eligible for inclusion in a meta-analysis. We combined results from the meta-analysis with the distribution of the values of FEV1 in CHASE to estimate the prevalence of children with abnormal lung function (FEV1<80% of predicted value) expected under different scenarios of NO2 exposure. In CHASE, there were non-significant inverse associations between all pollutants except ozone and both FEV1 and FVC. In the meta-analysis, a 10 μg/m3 increase in NO2 was associated with an 8 ml lower FEV1 (95% CI: -14 to -1 ml; p: 0.016). The observed effect was not modified by a reported asthma diagnosis. On the basis of these results, a 10 μg/m3 increase in NO2 level would translate into a 7% (95% CI: 4% to 12%) increase of the prevalence of children with abnormal lung function. CONCLUSIONS: Exposure to traffic pollution may cause a small overall reduction in lung function and increase the prevalence of children with clinically relevant declines in lung function

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Overnight switch from ropinirole to transdermal rotigotine patch in patients with Parkinson disease

<p>Abstract</p> <p>Background</p> <p>A recent trial involving predominantly Caucasian subjects with Parkinson Disease (PD) showed switching overnight from an oral dopaminergic agonist to the rotigotine patch was well tolerated without loss of efficacy. However, no such data have been generated for Korean patients.</p> <p>Methods</p> <p>This open-label multicenter trial investigated PD patients whose symptoms were not satisfactorily controlled by ropinirole, at a total daily dose of 3 mg to 12 mg, taken as monotherapy or as an adjunct to levodopa. Switching treatment from oral ropinirole to transdermal rotigotine was carried out overnight, with a dosage ratio of 1.5:1. After a 28-day treatment period, the safety and tolerability of switching was evaluated. Due to the exploratory nature of this trial, the effects of rotigotine on motor and nonmotor symptoms of PD were analyzed in a descriptive manner.</p> <p>Results</p> <p>Of the 116 subjects who received at least one treatment, 99 (85%) completed the 28-day trial period. Dose adjustments were required for 11 subjects who completed the treatment period. A total of 76 treatment-emergent adverse events (AEs) occurred in 45 subjects. No subject experienced a serious AE. Thirteen subjects discontinued rotigotine prematurely due to AEs. Efficacy results suggested improvements in both motor and nonmotor symptoms and quality of life after switching. Fifty-two subjects (46%) agreed that they preferred using the patch over oral medications, while 31 (28%) disagreed.</p> <p>Conclusions</p> <p>Switching treatment overnight from oral ropinirole to transdermal rotigotine patch, using a dosage ratio of 1.5:1, was well tolerated in Korean patients with no loss of efficacy.</p> <p>Trial registration</p> <p>This trial is registered with the ClincalTrails.gov Registry (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00593606">NCT00593606</a>).</p

Measurement of the flavour composition of dijet events in pp collisions at root s=7 TeV with the ATLAS detector

This paper describes a measurement of the flavour composition of dijet events produced in pp collisions at &#8730;s=7 TeV using the ATLAS detector. The measurement uses the full 2010 data sample, corresponding to an integrated luminosity of 39 pb−1. Six possible combinations of light, charm and bottom jets are identified in the dijet events, where the jet flavour is defined by the presence of bottom, charm or solely light flavour hadrons in the jet. Kinematic variables, based on the properties of displaced decay vertices and optimised for jet flavour identification, are used in a multidimensional template fit to measure the fractions of these dijet flavour states as functions of the leading jet transverse momentum in the range 40 GeV to 500 GeV and jet rapidity |y|&#60;2.1. The fit results agree with the predictions of leading- and next-to-leading-order calculations, with the exception of the dijet fraction composed of bottom and light flavour jets, which is underestimated by all models at large transverse jet momenta. The ability to identify jets containing two b-hadrons, originating from e.g. gluon splitting, is demonstrated. The difference between bottom jet production rates in leading and subleading jets is consistent with the next-to-leading-order predictions