Effect of insulin glargine on cardiovascular risk analysed by mean HRV

Type 2 diabetes mellitus is an insidious disease that is increasingly present in geriatric population [1]. The greatest difficulty is represented by glycaemic control in geriatric patients often not very compliant with diet therapy and drug therapy. A new insulin glargine 300 units/ml formulation seems im- prove patient compliance due to the lower volume of insulin to be injected and improved glycaemic control over 24 hours. The HRV signal, derived from digital electrocardiographic recording, is the simplest and most imme- diate analysis that consists in calculating some temporal parameters [2]. HRV is a simple statistics derived from beat-beat intervals of sinus origin expressed as units of time in milliseconds. Data in the literature indicate that a decrease in HRV, measured with time domain analysis, denotes a worse prognosis and/or an increased risk of mortality in patients with heart disease, especially in the elderly ones

Evaluation of HIV counseling and testing in ANC settings and adherence to short course antiretroviral prophylaxis for PMTCT in Francistown, Botswana

Worldwide, it is estimated that two million children are infected with HIV (USAID 2005). The vast majority of these infections are the result of mother-to-child transmission (MTCT) of the virus during pregnancy, labor, or breastfeeding. However, there are effective methods for prevention of mother-to-child transmission (PMTCT). Botswana is one of the first countries in the developing world with a national PMTCT program that uses an efficacious and complex regimen to reduce vertical transmission. At the time of this evaluation (August - December 2005), the standard of care for prevention of MTCT of HIV in Botswana included three-drug antiretroviral therapy for HIV-infected women with a CD4 count of 200 (300 mg AZT in the morning and 300 mg AZT in the evening); four weeks of AZT for their infants; single-dose maternal and infant nevirapine (NVP); and 12 months of free infant formula. Botswana's PMTCT program also provided routine HIV testing for all pregnant women during antenatal care (ANC) to identify HIV-positive women for prophylaxis or treatment. While programs often report the number of individuals beginning AZT and receiving nevirapine for PMTCT, effectiveness is dependent on the level of adherence of individuals to these regimens. To describe adherence of pregnant women to the current PMTCT regimen, the Horizons Program of the Population Council, in collaboration with the Centers for Disease Control and Prevention (CDC) and Premiere Personnel in Botswana, conducted an evaluation to describe HIV-related services provided to women during their pregnancies, document the content of post-test counseling sessions for HIV-positive pregnant women, whether HIV-positive women remembered what had been discussed, the extent of AZT adherence based on self-reports, and the operational successes and barriers to adherence to AZT for PMTCT

Assortative human pair-bonding for partner ancestry and allelic variation of the dopamine receptor D4 (DRD4) gene

The 7R allele of the dopamine receptor D4 gene has been associated with attention-deficit hyperactivity disorder and risk taking. On the cross-population scale, 7R allele frequencies have been shown to be higher in populations with more of a history of long-term migrations. It has also been shown that the 7R allele is associated with individuals having multiple-ancestries. Here we conduct a replication of this latter finding with two independent samples. Measures of subjects’ ancestry are used to examine past reproductive bonds. The individuals’ history of inter-racial/ancestral dating and their feelings about this are also assessed. Tentative support for an association between multiple ancestries and the 7R allele were found. These results are dependent upon the method of questioning subjects about their ancestries. Inter-racial dating and feelings about inter-racial pairing were not related to the presence of the 7R allele. This might be accounted for by secular trends that might have substantively altered the decision-making process employed when considering relationships with individuals from different groups. This study provides continued support for the 7R allele playing a role in migration and/or mate choice patterns. However, replications and extensions of this study are needed and must carefully consider how ancestry/race is assessed

Genetic variability detected at the lactoferrin locus (LTF) in the Italian Mediterranean river buffalo

Lactoferrin (LTF) is multi-functional protein belonging to the whey protein fractions of the milk. The gene LTF encoding for such protein is considered a potential candidate for body measurement, milk composition and yield. This study reports on the genetic variability at LTF locus in the Italian Mediterranean river buffalo and its possible association with milk yield. Eleven polymorphic sites were found in the DNA fragment spanning the exons 15-16. In particular, the intron 15 was extremely polymorphic with 9 SNPs detected, whereas the remaining 2 SNPs were exonic mutations (g.88G>A at the exon 15 and g.1351G>A at the exon 16) and both synonymous. The genotyping of the informative samples evidenced 3 haplotypes, whose frequencies were 0.6; 0.3 and 0.1 respectively, whereas the analysis of the exonic SNPs showed a perfect condition of linkage disequilibrium (g.88A/g.1351G and g.88G/g.1351A). The association study carried out by using the SNP g.88G>A showed that buffalo LTF gene has no statistically significant influence on daily milk yield. This study adds knowledge to the genetic variability of a species less investigated than the other ruminant species, that may serve as a useful tool for large-scale screening of buffalo populations

NMDA Receptor Phosphorylation at a Site Affected in Schizophrenia Controls Synaptic and Behavioral Plasticity

Phosphorylation of the NR1 subunit of NMDA receptors (NMDARs) at serine (S) 897 is markedly reduced in schizophrenia patients. However, the role of NR1 S897 phosphorylation in normal synaptic function and adaptive behaviors are unknown. To address these questions, we generated mice in which the NR1 S897 is replaced with alanine (A). This knock-in mutation causes severe impairment in NMDAR synaptic incorporation and NMDAR-mediated synaptic transmission. Furthermore, the phosphomutant animals have reduced AMPA receptor (AMPAR)-mediated synaptic transmission, decreased AMPAR GluR1 subunit in the synapse, and impaired long-term potentiation. Finally, the mutant mice exhibit behavioral deficits in social interaction and sensorimotor gating. Our results suggest that an impairment in NR1 phosphorylation leads to glutamatergic hypofunction that can contribute to behavioral deficits associated with psychiatric disorders

Francisella tularensis Schu S4 lipopolysaccharide core sugar and o-antigen mutants are attenuated in a mouse model of tularemia

The virulence factors mediating Francisella pathogenesis are being investigated, with an emphasis on understanding how the organism evades innate immunity mechanisms. Francisella tularensis produces a lipopolysaccharide (LPS) that is essentially inert and a polysaccharide capsule that helps the organism to evade detection by components of innate immunity. Using an F. tularensis Schu S4 mutant library, we identified strains that are disrupted for capsule and O-antigen production. These serum-sensitive strains lack both capsule production and O-antigen laddering. Analysis of the predicted protein sequences for the disrupted genes (FTT1236 and FTT1238c) revealed similarity to those for waa (rfa) biosynthetic genes in other bacteria. Mass spectrometry further revealed that these proteins are involved in LPS core sugar biosynthesis and the ligation of O antigen to the LPS core sugars. The 50% lethal dose (LD(50)) values of these strains are increased 100- to 1,000-fold for mice. Histopathology revealed that the immune response to the F. tularensis mutant strains was significantly different from that observed with wild-type-infected mice. The lung tissue from mutant-infected mice had widespread necrotic debris, but the spleens lacked necrosis and displayed neutrophilia. In contrast, the lungs of wild-type-infected mice had nominal necrosis, but the spleens had widespread necrosis. These data indicate that murine death caused by wild-type strains occurs by a mechanism different from that by which the mutant strains kill mice. Mice immunized with these mutant strains displayed >10-fold protective effects against virulent type A F. tularensis challenge

Acylation of the Lipooligosaccharide of Haemophilus influenzae and Colonization: an htrB Mutation Diminishes the Colonization of Human Airway Epithelial Cells

Haemophilus influenzae is a commensal and opportunistic pathogen of the human airways. A number of surface molecules contribute to colonization of the airways by H. influenzae, such as adhesins, including structures found in the lipooligosaccharide (LOS). A human bronchiolar xenograft model was employed to investigate the host-bacterial interactions involved in the colonization of the airway by H. influenzae. Differential display was used to identify H. influenzae mRNA that reflect genes which were preferentially expressed in the xenograft compared to growth. Eleven mRNA fragments had consistent increased expression when the bacteria grew in xenografts. On sequencing these fragments, eight open reading frames were identified. Three of these had no match in the NCBI or the TIGR database, while an additional three were homologous to genes involved in heme or iron acquisition and utilization: two of the mRNAs encoded proteins homologous to enzymes involved in LOS biosynthesis: a heptosyl transferase (rfaF) involved in the synthesis of the LOS core and a ketodeoxyoctonate phosphate-dependent acyltransferase (htrB) that performs one of the late acylation reactions in lipid A synthesis. Inoculation of human bronchiolar xenografts revealed a significant reduction in colonization capacity by htrB mutants. In vitro, htrB mutants elicited lesser degrees of cytoskeletal rearrangement and less stimulation of host cell signaling with 16HBE14o- cells and decreased intracellular survival. These results implicate acylation of H. influenzae lipid A as playing a key role in the organisms' colonization of the normal airway

Ordered interfaces for dual easy axes in liquid crystals

International audienceUsing nCB films adsorbed on MoS 2 substrates studied by x-ray diffraction, optical microscopy and Scanning Tunneling Microscopy, we demonstrate that ordered interfaces with well-defined orientations of adsorbed dipoles induce planar anchoring locked along the adsorbed dipoles or the alkyl chains, which play the role of easy axes. For two alternating orientations of the adsorbed dipoles or dipoles and alkyl chains, bi-stability of anchoring can be obtained. The results are explained using the introduction of fourth order terms in the phenomenological anchoring potential, leading to the demonstration of first order anchoring transition in these systems. Using this phenomenological anchoring potential, we finally show how the nature of anchoring in presence of dual easy axes (inducing bi-stability or average orientation between the two easy axes) can be related to the microscopical nature of the interface. Introduction Understanding the interactions between liquid crystal (LC) and a solid substrate is of clear applied interest, the vast majority of LC displays relying on control of interfaces. However this concerns also fundamental problems like wetting phenomena and all phenomena of orientation of soft matter bulk induced by the presence of an interface. In LCs at interfaces, the so-called easy axes correspond to the favoured orientations of the LC director close to the interface. If one easy axis only is defined for one given interface, the bulk director orients along or close to this axis [1]. It is well known that, in anchoring phenomena, two major effects compete to impose the anchoring directions of a liquid crystal, first, the interactions between molecules and the interface, second, the substrate roughness whose role has been analyzed by Berreman [2]. The influence of adsorbed molecular functional groups at the interface is most often dominant with, for example in carbon substrates, a main influence of unsaturated carbon bonds orientation at the interface [3]. In common LC displays, there is one unique easy axis, but modifications of surfaces have allowed for the discovery of promising new anchoring-related properties. For instance, the first anchoring bi-stability has been established on rough surfaces, associated with electric ordo-polarization [4] and the competition between a stabilizing short-range term and a destabilizing long-range term induced by an external field, can induce a continuous variation of anchoring orientation [5]. More recently, surfaces with several easy axes have been studied extensively. It has been shown that control of a continuous variation of director pretilt, obtained in several systems [6, 7], is associated with the presence of two different easy axes, one perpendicular to the substrate (homeotropic) and one planar [7, 8]. Similar models can explain the continuous evolution of anchoring between two planar orientations observed on some crystalline substrates [9]. However, in the same time, two easy axes can also lead to anchoring bi-stability [10, 11] or discontinuous transitions of anchoring [9], which is not compatible with the model established to interpret observed control of pretilt. In order to be able to predict if bi-stability or continuous combination of the two easy axes occurs for one given system, it becomes necessary to understand the microscopic origin of the easy axes

Classification of autism spectrum disorder using supervised learning of brain connectivity measures extracted from synchrostates

This is the author accepted manuscript. The final version is available from IOP Publishing via the DOI in this record.OBJECTIVE: The paper investigates the presence of autism using the functional brain connectivity measures derived from electro-encephalogram (EEG) of children during face perception tasks. APPROACH: Phase synchronized patterns from 128-channel EEG signals are obtained for typical children and children with autism spectrum disorder (ASD). The phase synchronized states or synchrostates temporally switch amongst themselves as an underlying process for the completion of a particular cognitive task. We used 12 subjects in each group (ASD and typical) for analyzing their EEG while processing fearful, happy and neutral faces. The minimal and maximally occurring synchrostates for each subject are chosen for extraction of brain connectivity features, which are used for classification between these two groups of subjects. Among different supervised learning techniques, we here explored the discriminant analysis and support vector machine both with polynomial kernels for the classification task. MAIN RESULTS: The leave one out cross-validation of the classification algorithm gives 94.7% accuracy as the best performance with corresponding sensitivity and specificity values as 85.7% and 100% respectively. SIGNIFICANCE: The proposed method gives high classification accuracies and outperforms other contemporary research results. The effectiveness of the proposed method for classification of autistic and typical children suggests the possibility of using it on a larger population to validate it for clinical practice.The work presented in this paper was supported by FP7 EU funded MICHELANGELO project, Grant Agreement #288241. URL: www.michelangelo-project.eu/