Reduction of cytochrome C oxidase during vasovagal hypoxia-ischemia in human adult brain: a case study

Near-infrared spectroscopy (NIRS)-derived measurement of oxidized cytochrome c oxidase concentration ([oxCCO]) has been used as an assessment of the adequacy of cerebral oxygen delivery. We report a case in which a reduction in conscious level was associated with a reduction in [oxCCO]. Hypoxaemia was induced in a 31-year-old, healthy male subject as part of an ongoing clinical study. Midway through the hypoxaemic challenge, the subject experienced an unexpected vasovagal event with bradycardia, hypotension and reduced cerebral blood flow (middle cerebral artery blood flow velocity decrease from 70 to 30 cm s(-1)) that induced a brief reduction in conscious level. An associated decrease in [oxCCO] was observed at 35 mm (-1.6 μM) but only minimal change (-0.1 μM) at 20-mm source-detector separation. A change in optical scattering was observed, but path length remained unchanged. This unexpected physiological event provides an unusual example of a severe reduction in cerebral oxygen delivery and is the first report correlating change in clinical status with changes in [oxCCO]

Irreversible reorganization in a supercooled liquid originates from localised soft modes

The transition of a fluid to a rigid glass upon cooling is a common route of transformation from liquid to solid that embodies the most poorly understood features of both phases1,2,3. From the liquid perspective, the puzzle is to understand stress relaxation in the disordered state. From the perspective of solids, the challenge is to extend our description of structure and its mechanical consequences to materials without long range order. Using computer simulations, we show that the localized low frequency normal modes of a configuration in a supercooled liquid are causally correlated to the irreversible structural reorganization of the particles within that configuration. We also demonstrate that the spatial distribution of these soft local modes can persist in spite of significant particle reorganization. The consequence of these two results is that it is now feasible to construct a theory of relaxation length scales in glass-forming liquids without recourse to dynamics and to explicitly relate molecular properties to their collective relaxation.Comment: Published online: 20 July 2008 | doi:10.1038/nphys1025 Available from http://www.nature.com/nphys/journal/v4/n9/abs/nphys1025.htm

Associations between SNPs and immune-related circulating proteins in schizophrenia

Genome-wide association studies (GWAS) and proteomic studies have provided convincing evidence implicating alterations in immune/inflammatory processes in schizophrenia. However, despite the convergence of evidence, direct links between the genetic and proteomic findings are still lacking for schizophrenia. We investigated associations between single nucleotide polymorphisms (SNPs) from the custom-made PsychArray and the expression levels of 190 multiplex immunoassay profiled serum proteins in 149 schizophrenia patients and 198 matched controls. We identified associations between 81 SNPs and 29 proteins, primarily involved in immune/inflammation responses. Significant SNPxDiagnosis interactions were identified for eight serum proteins including Factor-VII[rs555212], Alpha-1-Antitrypsin[rs11846959], Interferon-Gamma Induced Protein 10[rs4256246] and von-Willebrand-Factor[rs12829220] in the control group; Chromogranin-A[rs9658644], Cystatin-C[rs2424577] and Vitamin K-Dependent Protein S[rs6123] in the schizophrenia group; Interleukin-6 receptor[rs7553796] in both the control and schizophrenia groups. These results suggested that the effect of these SNPs on expression of the respective proteins varies with diagnosis. The combination of patient-specific genetic information with blood biomarker data opens a novel approach to investigate disease mechanisms in schizophrenia and other psychiatric disorders. Our findings not only suggest that blood protein expression is influenced by polymorphisms in the corresponding gene, but also that the effect of certain SNPs on expression of proteins can vary with diagnosis

Household Transmission of Rotavirus in a Community with Rotavirus Vaccination in Quininde, Ecuador

Background: We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era. Methods: Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics) and susceptibility (householdcontact characteristics). Results: Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR) were 55%, 8% and 2%, (n = 137, 130, 137) respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was ,18 months and had vomiting, with household contact ,10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission. Conclusion: Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case) and susceptibility (young age/sharing a room/being a sibling of the index case). Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees

Evidence for a fractional quantum Hall state with anisotropic longitudinal transport

At high magnetic fields, where the Fermi level lies in the N=0 lowest Landau level (LL), a clean two-dimensional electron system (2DES) exhibits numerous incompressible liquid phases which display the fractional quantized Hall effect (FQHE) (Das Sarma and Pinczuk, 1997). These liquid phases do not break rotational symmetry, exhibiting resistivities which are isotropic in the plane. In contrast, at lower fields, when the Fermi level lies in the $N\ge2$ third and several higher LLs, the 2DES displays a distinctly different class of collective states. In particular, near half filling of these high LLs the 2DES exhibits a strongly anisotropic longitudinal resistance at low temperatures (Lilly et al., 1999; Du et al., 1999). These "stripe" phases, which do not exhibit the quantized Hall effect, resemble nematic liquid crystals, possessing broken rotational symmetry and orientational order (Koulakov et al., 1996; Fogler et al., 1996; Moessner and Chalker, 1996; Fradkin and Kivelson, 1999; Fradkin et al, 2010). Here we report a surprising new observation: An electronic configuration in the N=1 second LL whose resistivity tensor simultaneously displays a robust fractionally quantized Hall plateau and a strongly anisotropic longitudinal resistance resembling that of the stripe phases.Comment: Nature Physics, (2011

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

Modeling concept drift: A probabilistic graphical model based approach

An often used approach for detecting and adapting to concept drift when doing classi cation is to treat the data as i.i.d. and use changes in classi cation accuracy as an indication of concept drift. In this paper, we take a different perspective and propose a framework, based on probabilistic graphical models, that explicitly represents concept drift using latent variables. To ensure effcient inference and learning, we resort to a variational Bayes inference scheme. As a proof of concept, we demonstrate and analyze the proposed framework using synthetic data sets as well as a real fi nancial data set from a Spanish bank

Double-Stranded RNA Attenuates the Barrier Function of Human Pulmonary Artery Endothelial Cells

Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed the effects of double stranded RNA on primary human pulmonary artery endothelial cells (hPAECs). The effect of natural and synthetic double-stranded RNA (dsRNA) on hPAECs was investigated using trans-endothelial electric resistance, molecule trafficking, calcium (Ca2+) homeostasis, gene expression and proliferation studies. Furthermore, the morphology and mechanical changes of the cells caused by synthetic dsRNA was followed by in-situ atomic force microscopy, by vascular-endothelial cadherin and F-actin staining. Our results indicated that exposure of hPAECs to synthetic dsRNA led to functional deficits. This was reflected by morphological and mechanical changes and an increase in the permeability of the endothelial monolayer. hPAECs treated with synthetic dsRNA accumulated in the G1 phase of the cell cycle. Additionally, the proliferation rate of the cells in the presence of synthetic dsRNA was significantly decreased. Furthermore, we found that natural and synthetic dsRNA modulated Ca2+ signaling in hPAECs by inhibiting the sarco-endoplasmic Ca2+-ATPase (SERCA) which is involved in the regulation of the intracellular Ca2+ homeostasis and thus cell growth. Even upon synthetic dsRNA stimulation silencing of SERCA3 preserved the endothelial monolayer integrity. Our data identify novel mechanisms by which dsRNA can disrupt endothelial barrier function and these may be relevant in inflammatory processes

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

<b>Background</b><p></p> It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.<p></p> <b>Methods</b><p></p> Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.<p></p> <b>Results</b><p></p> There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.<p></p> <b>Conclusions</b><p></p> Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes