Combined spinal-epidural anesthesia for cesarean section in a patient with Moyamoya disease -A case report-

Moyamoya disease is a rare progressive occlusive disease of the internal carotid arteries. We report a case of combined spinal-epidural anesthesia in a patient with Moyamoya disease presenting for Cesarean section. Hypotension associated with spinal anesthesia for Cesarean section is the most common and serious adverse effect despite the use of uterine displacement and volume preload. We continuously infused phenylephrine and ephedrine to prevent hypotension. The intraoperative hemodynamic state was stable. The patient had no significant postoperative complications

Radical genome remodelling accompanied the emergence of a novel host-restricted bacterial pathogen

The emergence of new pathogens is a major threat to public and veterinary health. Changes in bacterial habitat such as a switch in host or disease tropism are typically accompanied by genetic diversification. Staphylococcus aureus is a multi-host bacterial species associated with human and livestock infections. A microaerophilic subspecies, Staphylococcus aureus subsp. anaerobius, is responsible for Morel’s disease, a lymphadenitis restricted to sheep and goats. However, the evolutionary history of S. aureus subsp. anaerobius and its relatedness to S. aureus are unknown. Population genomic analyses of clinical S. aureus subsp. anaerobius isolates revealed a highly conserved clone that descended from a S. aureus progenitor about 1000 years ago before differentiating into distinct lineages that contain African and European isolates. S. aureus subsp. anaerobius has undergone limited clonal expansion, with a restricted population size, and an evolutionary rate 10-fold slower than S. aureus. The transition to its current restricted ecological niche involved acquisition of a pathogenicity island encoding a ruminant host-specific effector of abscess formation, large chromosomal re-arrangements, and the accumulation of at least 205 pseudogenes, resulting in a highly fastidious metabolism. Importantly, expansion of ~87 insertion sequences (IS) located largely in intergenic regions provided distinct mechanisms for the control of expression of flanking genes, including a novel mechanism associated with IS-mediated anti-anti-sense decoupling of ancestral gene repression. Our findings reveal the remarkable evolutionary trajectory of a host-restricted bacterial pathogen that resulted from extensive remodelling of the S. aureus genome through an array of diverse mechanisms in parallel

Chitosan and its derivatives as nanocarriers for siRNA delivery

The ability to specifically silence genes using siRNA has enormous potential for treating genetic diseases. However, siRNA instability and biodistribution issues still need to be overcome, and adequate delivery vehicles have proven indispensable in conveying siRNA to its target. Chitosan is a promising biopolymer for siRNA delivery, its interest stemming from its safety, biodegradability, mucoadhesivity, permeation enhancing effect and cationic charge, as well as amenability to undergo chemical modifications. Chitosan and its derivatives can be readily arranged into complexes or nanoparticles able to entrap and carry siRNA. Specific strategies have been adopted to improve chitosan-based vectors with regard to transfectability. However, further efforts are required to verify their value and adapt them to enhance therapeutic output prior to clinical application. This review emphasizes the potential of chitosan and its derivatives to develop nanocarriers for siRNA delivery. The properties of chitosan that are significant for transfectability and the most relevant findings are assessed

Mitochondrial Function and Dysfunction in Dilated Cardiomyopathy

Cardiac tissue requires a persistent production of energy in order to exert its pumping function. Therefore, the maintenance of this function relies on mitochondria that represent the "powerhouse" of all cardiac activities. Mitochondria being one of the key players for the proper functioning of the mammalian heart suggests continual regulation and organization. Mitochondria adapt to cellular energy demands via fusion-fission events and, as a proof-reading ability, undergo mitophagy in cases of abnormalities. Ca2+ fluxes play a pivotal role in regulating all mitochondrial functions, including ATP production, metabolism, oxidative stress balance and apoptosis. Communication between mitochondria and others organelles, especially the sarcoplasmic reticulum is required for optimal function. Consequently, abnormal mitochondrial activity results in decreased energy production leading to pathological conditions. In this review, we will describe how mitochondrial function or dysfunction impacts cardiac activities and the development of dilated cardiomyopathy

A meta-analysis reveals the commonalities and differences in Arabidopsis thaliana response to different viral pathogens

Understanding the mechanisms by which plants trigger host defenses in response to viruses has been a challenging problem owing to the multiplicity of factors and complexity of interactions involved. The advent of genomic techniques, however, has opened the possibility to grasp a global picture of the interaction. Here, we used Arabidopsis thaliana to identify and compare genes that are differentially regulated upon infection with seven distinct (+)ssRNA and one ssDNA plant viruses. In the first approach, we established lists of genes differentially affected by each virus and compared their involvement in biological functions and metabolic processes. We found that phylogenetically related viruses significantly alter the expression of similar genes and that viruses naturally infecting Brassicaceae display a greater overlap in the plant response. In the second approach, virus-regulated genes were contextualized using models of transcriptional and protein-protein interaction networks of A. thaliana. Our results confirm that host cells undergo significant reprogramming of their transcriptome during infection, which is possibly a central requirement for the mounting of host defenses. We uncovered a general mode of action in which perturbations preferentially affect genes that are highly connected, central and organized in modules. © 2012 Rodrigo et al.This work was supported by the Spanish Ministerio de Ciencia e Innovacion (MICINN) grants BFU2009-06993 (S. F. E.) and BIO2006-13107 (C. L.) and by Generalitat Valenciana grant PROMETEO2010/016 (S. F. E.). G. R. is supported by a graduate fellowship from the Generalitat Valenciana (BFPI2007-160) and J.C. by a contract from MICINN grant TIN2006-12860. 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Metagenomic Profile of the Bacterial Communities Associated with Ixodes ricinus Ticks

Assessment of the microbial diversity residing in arthropod vectors of medical importance is crucial for monitoring endemic infections, for surveillance of newly emerging zoonotic pathogens, and for unraveling the associated bacteria within its host. The tick Ixodes ricinus is recognized as the primary European vector of disease-causing bacteria in humans. Despite I. ricinus being of great public health relevance, its microbial communities remain largely unexplored to date. Here we evaluate the pathogen-load and the microbiome in single adult I. ricinus by using 454- and Illumina-based metagenomic approaches. Genomic DNA-derived sequences were taxonomically profiled using a computational approach based on the BWA algorithm, allowing for the identification of known tick-borne pathogens at the strain level and the putative tick core microbiome. Additionally, we assessed and compared the bacterial taxonomic profile in nymphal and adult I. ricinus pools collected from two distinct geographic regions in Northern Italy by means of V6-16S rRNA amplicon pyrosequencing and community based ecological analysis. A total of 108 genera belonging to representatives of all bacterial phyla were detected and a rapid qualitative assessment for pathogenic bacteria, such as Borrelia, Rickettsia and Candidatus Neoehrlichia, and for other bacteria with mutualistic relationship or undetermined function, such as Wolbachia and Rickettsiella, was possible. Interestingly, the ecological analysis revealed that the bacterial community structure differed between the examined geographic regions and tick life stages. This finding suggests that the environmental context (abiotic and biotic factors) and host-selection behaviors affect their microbiome

Role of IKK/NF-κB Signaling in Extinction of Conditioned Place Aversion Memory in Rats

The inhibitor κB protein kinase/nuclear factor κB (IKK/NF-κB) signaling pathway is critical for synaptic plasticity. However, the role of IKK/NF-κB in drug withdrawal-associated conditioned place aversion (CPA) memory is unknown. Here, we showed that inhibition of IKK/NF-κB by sulphasalazine (SSZ; 10 mM, i.c.v.) selectively blocked the extinction but not acquisition or expression of morphine-induced CPA in rats. The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase. Thus, the IKK/NF-κB signaling pathway might play a critical role in the extinction of morphine-induced CPA in rats and might be a potential pharmacotherapy target for opiate addiction

Genetic Control of a Central Pattern Generator: Rhythmic Oromotor Movement in Mice Is Controlled by a Major Locus near Atp1a2

Fluid licking in mice is a rhythmic behavior that is controlled by a central pattern generator (CPG) located in a complex of brainstem nuclei. C57BL/6J (B6) and DBA/2J (D2) strains differ significantly in water-restricted licking, with a highly heritable difference in rates (h2≥0.62) and a corresponding 20% difference in interlick interval (mean ± SEM = 116.3±1 vs 95.4±1.1 ms). We systematically quantified motor output in these strains, their F1 hybrids, and a set of 64 BXD progeny strains. The mean primary interlick interval (MPI) varied continuously among progeny strains. We detected a significant quantitative trait locus (QTL) for a CPG controlling lick rate on Chr 1 (Lick1), and a suggestive locus on Chr 10 (Lick10). Linkage was verified by testing of B6.D2-1D congenic stock in which a segment of Chr 1 of the D2 strain was introgressed onto the B6 parent. The Lick1 interval on distal Chr 1 contains several strong candidate genes. One of these is a sodium/potassium pump subunit (Atp1a2) with widespread expression in astrocytes, as well as in a restricted population of neurons. Both this subunit and the entire Na+/K+-ATPase molecule have been implicated in rhythmogenesis for respiration and locomotion. Sequence variants in or near Apt1a2 strongly modulate expression of the cognate mRNA in multiple brain regions. This gene region has recently been sequenced exhaustively and we have cataloged over 300 non-coding and synonymous mutations segregating among BXD strains, one or more of which is likely to contribute to differences in central pattern generator tempo

The positive role of hope on the relationship between loneliness and unhappy conditions in Hungarian young adults: How pathways thinking matters!

In this study, we examined loneliness and hope components as predictors of unhappy conditions (viz., anxious symptoms, depressive symptoms, & suicidal ideation) in young adults. The sample was comprised of 489 Hungarian college students. Results of conducting hierarchical regression analyses indicated that loneliness and hope pathways (but not hope agency) were important unique predictors of anxious symptoms, depressive symptoms, and suicidal ideation. Moreover, in part, consistent with the notion that hope might buffer the negative effects of loneliness on unhappy conditions, evidence for a significant Loneliness × Hope Pathways interaction effect in predicting each of the three indices of unhappy conditions was found. In contrast, the Loneliness × Hope Agency interaction effect was not found to be significant. Some implications of the present findings for the study and treatment of unhappy conditions in adults are discussed