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

The (Mis)Reporting of Male Circumcision Status among Men and Women in Zambia and Swaziland: A Randomized Evaluation of Interview Methods

BACKGROUND: To date, male circumcision prevalence has been estimated using surveys of men self-reporting their circumcision status. HIV prevention trials and observational studies involving female participants also collect data on partners' circumcision status as a risk factor for HIV/STIs. A number of studies indicate that reports of circumcision status may be inaccurate. This study assessed different methods for improving self- and partner reporting of circumcision status. METHODS/FINDINGS: The study was conducted in urban and rural Zambia and urban Swaziland. Men (N = 1264) aged 18-50 and their female partners (N = 1264), and boys (N = 840) aged 13-17 were enrolled. Participants were recruited from HIV counseling and testing sites, health centers, and surrounding communities. The study experimentally assessed methods for improving the reporting of circumcision status, including: a) a simple description of circumcision, b) a detailed description of circumcision, c) an illustration of a circumcised and uncircumcised penis, and d) computerized self-interviewing. Self-reports were compared to visual examination. For men, the error in reporting was largely unidirectional: uncircumcised men more often reported they were circumcised (2-7%), depending on setting. Fewer circumcised men misrepresented their status (0.05-5%). Misreporting by women was significantly higher (11-15%), with the error in both directions. A sizable number of women reported that they did not know their partner's circumcision status (3-8%). Computerized interviewing did not improve accuracy. Providing an illustration, particularly for illiterate participants, significantly improved reporting of circumcision status, decreasing misreporting among illiterate participants from 13% to 10%, although misreporting was not eliminated. CONCLUSIONS: Study results suggest that the prevalence of circumcision may be overestimated in Zambia and Swaziland; the error in reporting is higher among women than among men. Improved reporting when a description or illustration is provided suggests that the source of the error is a lack of understanding of male circumcision

Bioresorption control and biological response of magnesium alloy az31 coated with poly-β-hydroxybutyrate

Magnesium and its alloys are not normally used as bioresorbable temporary implants due to their high and uncontrolled degradation rate in a physiological liquid environment. The improvement of corrosion resistance to simulated body fluids (SBF) of a magnesium alloy (AZ31) coated with poly-β-hydroxybutyrate (PHB) was investigated. Scanning electron microscopy, Fourier transform infrared spectrometer, and contact angle measurements were used to characterize surface morphology, material composition, and wettability, respectively. pH modification of the SBF corroding medium, mass of Mg2+ ions released, weight loss of the samples exposed to the SBF solution, and electrochemical experiments were used to describe the corrosion process and its kinetics. The material’s biocompatibility was described by evaluating the effect of corrosion by products collected in the SBF equilibrating solution on hemolysis ratio, cytotoxicity, nitric oxide (NO), and total antioxidant capacity (T-AOC). The results showed that the PHB coating can diffusively control the degradation rate of magnesium alloy, improving its biocompatibility: the hemolysis rate of materials was lower than 5%, while in vitro human umbilical vein endothelial cell (HUVEC) compatibility experiments showed that PHB-coated Mg alloy promoted cell proliferation and had no effect on the NO content and that the T-AOC was enhanced compared with the normal group and bare AZ31 alloy. PHB-coated AZ31 magnesium alloy extraction fluids have a less toxic behavior due to the lower concentration of corrosion byproducts deriving from the diffusion control exerted by the PHB coating films both from the metal surface to the solution and vice versa. These findings provide more reference value for the selection of such systems as tunable bioresorbable prosthetic materials

Optical Properties of Organic Carbon and Soot Produced in an Inverse Diffusion Flame

The carbonaceous matter (soot plus organic carbon) sampled downstream of an ethylene inverse diffusion flame (IDF) was chemically and spectroscopically analyzed in detail. In particular, the H/C ratio, the UV-Visible absorption coefficient and Raman parameters were measured and found to be representative of a highly disordered sp2 -rich carbon as the early soot sampled in a premixed flame. In contrast, the optical band gap was found to be relatively low (0.7eV), closer to the optical band gap of graphite than to that of medium-sized polycyclic aromatic hydrocarbons (\u3e2eV) which are widely considered to be soot precursors and are mostly contained in the organic carbon. The significance of the optical band gap as signature of different structural levels (nano-, micro- and macro-structure) of sp2 -rich aromatic disordered carbons was critically analyzed in reference to their molecular weight/size distribution. The relevance of the optical band analysis to the study of the soot formation mechanism was also highlighted

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/

Characterization and sequence analysis of the lsg (LOS synthesis genes) locus from Haemophilus influenzae type b

Analysis of the lsg (LOS synthesis genes) cluster in Escherichia coli strain K12 and mutations in the lsg locus in Haemophilus influenzae type b indicated the presence of 3 regions responsible for sequential modifications of E. coli lipopolysaccharide (LPS). Sequencing of the lsg region yielded 7,435 bp that encompassed 7 complete and 1 partial open reading frames (ORFs 1-8). The predicted product of ORF1 had homology to the consensus sequence of cytochrome b proteins (21% identity, 51% similarity) and to other transmembrane proteins. The products of ORF5 and ORF6 share overall 23% identity and 49% similarity with each other. The ORF6 protein had high homology with the product of ORF275 of the E. coli rfb gene cluster (40% identity, 58% similarity), whose function is not known. Multiple sequence alignment of the ORF5 and ORF6 proteins with the RfbB, RfbJ and RfbX proteins revealed conserved motifs over the N-terminal half region of all these proteins. The products of ORF7 and ORF8 are homologous with Azotobacter vinelandii MolA protein (30% identity, 51% similarity) and MolB protein (26% identity, 48% similarity), respectively. The promoter regions of ORF1, 7 and 8 were determined by primer extension analysis and found to be similar to bacterial σ70-dependent promoters. ORF7 and ORF8 are transcribed into diverse orientation. At least 5 of the encoded proteins have been identified using coupled E. coli transcription/translation system and labeling with [35S]-methionine. We conclude that the genetic organization of the lsg biosynthesis pathway involves multiple operons that lead to the assembly of an H. influenzae LOS structure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67077/2/10.1177_096805199400100305.pd

Enhancement of SSVEPs Classification in BCI-based Wearable Instrumentation Through Machine Learning Techniques

This work addresses the adoption of Machine Learning classifiers and Convolutional Neural Networks to improve the performance of highly wearable, single-channel instrumentation for Brain-Computer Interfaces. The proposed measurement system is based on the classification of Steady-State Visually Evoked Potentials (SSVEPs). In particular, Head-Mounted Displays for Augmented Reality are used to generate and display the flickering stimuli for the SSVEPs elicitation. Four experiments were conducted by employing, in turn, a different Head-Mounted Display. For each experiment, two different algorithms were applied and compared with the state-of-the-art-techniques. Furthermore, the impact of different Augmented Reality technologies in the elicitation and classification of SSVEPs was also explored. The experimental metrological characterization demonstrates (i) that the proposed Machine Learning-based processing strategies provide a significant enhancement of the SSVEP classification accuracy with respect to the state of the art, and (ii) that choosing an adequate Head-Mounted Display is crucial to obtain acceptable performance. Finally, it is also shown that the adoption of inter-subjective validation strategies such as the Leave-One-Subject-Out Cross Validation successfully leads to an increase in the inter-individual 1-σ reproducibility: this, in turn, anticipates an easier development of ready-to-use systems

Prolyl 3‐hydroxylase 2 is a molecular player of angiogenesis

Prolyl 3‐hydroxylase 2 (P3H2) catalyzes the post‐translational formation of 3‐ hydroxyproline on collagens, mainly on type IV. Its activity has never been directly associated to angiogenesis. Here, we identified P3H2 gene through a deep‐sequencing transcriptome analysis of human umbilical vein endothelial cells (HUVECs) stimulated with vascular endothelial growth factor A (VEGF‐A). Differently from many previous studies we carried out the stimulation not on starved HUVECs, but on cells grown to maintain the best condition for their in vitro survival and propagation. We showed that P3H2 is induced by VEGF‐A in two primary human endothelial cell lines and that its transcription is modulated by VEGF‐A/VEGF receptor 2 (VEGFR‐2) signaling pathway through p38 mitogen‐activated protein kinase (MAPK). Then, we demonstrated that P3H2, through its activity on type IV Collagen, is essential for angiogenesis properties of endothelial cells in vitro by performing experiments of gain‐ and loss‐of‐function. Immunofluorescence studies showed that the overexpression of P3H2 induced a more condensed status of Collagen IV, accompanied by an alignment of the cells along the Collagen IV bundles, so towards an evident pro‐angiogenic status. Finally, we found that P3h2 knockdown prevents pathological angiogenesis in vivo, in the model of laser‐induced choroid neovascularization. Together these findings reveal that P3H2 is a new molecular player involved in new vessels formation and could be considered as a potential target for anti‐angiogenesis therapy

Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications.

BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values - assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical "BCR/ABL1-like predictor", for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the "BCR/ABL1-like predictor", we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis

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