A course of acute respiratory virus infections in patients with metabolic syndrome

AIM: To determine specific features of a course of acute respiratory viral infections (ARVI) and changes in immunological status in patients with metabolic syndrome (MS). MATERIAL AND METHODS: Body mass index (BMI), waist circumference, levels of cholesterol, lipoproteins, triglycerides, cytokines and immunoglobulins were measured and glucose tolerance test was made in 120 patients with MS. Registration of ARVI during a year was verified by the presence of antigens in immunofluorescence reaction. RESULTS: MS patients have obesity of an abdominal type and immunoresistance. Concentration of proinflammatory cytokines and leukocyte count in blood increased proportionally to an increase in fat tissue mass, immunoglobulins content went down. ARVI in most evident MS were characterized by a sluggish and areactive onset, longer course, more frequent respiratory and cardiovascular complications. CONCLUSION: MS is a factor of risk of a sluggish and complicated course of ARVI.     

Hydrogen Gas Phase and Electrochemical Hydriding of LaNi5−xMx (M = Sn,Co, Al) Alloys

Hydriding/dehydriding properties of a series of LaNi₅ based alloys were compared by applying both hydrogen gas phase and electrochemical hydrogen charge/discharge methods. The highest hydrogen absorption capacity of 1.4 wt.% H₂ was found for LaNi_4.3Co_0.4Al_0.3, although LaNi_4.8Sn_0.2 also reveals comparable hydrogen capacity (>1.3%). A significant difference in the hydriding kinetics was observed for all studied alloys before and after activation. The activated alloys (5 cycles at 65 °C, 40 atm. H₂) reach their maximum capacities after less than a minute, whereas the pure LaNi₅ alloy needs several minutes for complete hydriding. The electrochemical hydriding/dehydriding behavior of the alloys reveals superior performance of LaNi_4.3Co_0.4Al_0.3 and LaNi_4.8Sn_0.2 compared to the other compositions studied, as the capacity of LaNi_4.8Sn_0.2 decreases by only 10% for 60 charge/discharge cycles at a current density of 100 mA/g. Good agreement between the hydrogen sorption kinetics of the alloys obtained electrochemically and from hydrogen gas phase has also been observed.     

Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.     

Trajectories of glycaemia following acute pancreatitis: a prospective longitudinal cohort study with 24 months follow-up

Journal of Gastroenterology - New-onset diabetes is the most common sequela of acute pancreatitis (AP). Yet, prospective changes in glycaemia over time have never been investigated comprehensively...     

Genome-wide signals of positive selection in human evolution

The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci, and the genome-wide patterns of polymorphism show signatures consistent with frequent positive selection. On the other hand, recent studies have argued that many of the candidate loci are false positives and that most genome-wide signatures of adaptation are in fact due to reduction of neutral diversity by linked deleterious mutations, known as background selection. Here we analyze human polymorphism data from the 1000 Genomes Project and detect signatures of positive selection once we correct for the effects of background selection. We show that levels of neutral polymorphism are lower near amino acid substitutions, with the strongest reduction observed specifically near functionally consequential amino acid substitutions. Furthermore, amino acid substitutions are associated with signatures of recent adaptation that should not be generated by background selection, such as unusually long and frequent haplotypes and specific distortions in the site frequency spectrum. We use forward simulations to argue that the observed signatures require a high rate of strongly adaptive substitutions near amino acid changes. We further demonstrate that the observed signatures of positive selection correlate better with the presence of regulatory sequences, as predicted by the ENCODE Project Consortium, than with the positions of amino acid substitutions. Our results suggest that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson that adaptive divergence is primarily driven by regulatory changes.The rate and patterns of positive selection are of fundamental interest for the study of human evolution. Population genomic studies should, in principle, allow us to quantify positive selection from its expected signatures in sequence polymorphism and divergence data. Surprisingly, despite the sequencing of thousands of human genomes (The 1000 Genomes Project Consortium 2012) and the availability of whole-genome sequences of closely related species, the extent to which adaptation has left identifiable signatures in the patterns of polymorphism in the human genome remains highly controversial (Akey 2009; Hernandez et al. 2011).On the one hand, recent studies have identified a large number of loci showing signatures of recent selective sweeps (Voight et al. 2006; Sabeti et al. 2007; Williamson et al. 2007; Pickrell et al. 2009; Grossman et al. 2013), and McDonald-Kreitman (MK) analyses inferred that ∼10%–20% of amino acid changes have been adaptive in human evolution (Boyko et al. 2008; Messer and Petrov 2013). Consistently, regions of high functional density, high rate of amino acid substitutions, and low recombination all show reduced levels of neutral diversity (Cai et al. 2009; Lohmueller et al. 2011), as expected under recurrent selective sweeps in functional regions.On the other hand, there are reasons to question the notion that adaptation left clear signatures in the human genome. First, different scans for positive selection have identified largely nonoverlapping sets of candidates (Akey 2009), which could be due to a high rate of false positives. Second, MK analyses can be confounded by a number of factors, such as perturbations left by demographic events and by the presence of slightly deleterious mutations (Eyre-Walker and Keightley 2009; Messer and Petrov 2013), and some MK analyses have failed to find evidence for adaptation in the human lineage (Eyre-Walker and Keightley 2009). Finally, it has been shown that background selection (BGS) (Charlesworth et al. 1993), a process in which deleterious mutations remove linked neutral variation from the population, reduces levels of polymorphism in regions of higher functional density and low recombination, providing an alternative explanation for the observation of these correlations in the human genome.One signature of positive selection—lower levels of neutral variation near functional substitutions (Andolfatto 2007; Macpherson et al. 2007; Cai et al. 2009)—is not generally expected under BGS and should therefore provide the clearest genomic evidence for the action of positive selection. While this signature was found in the human genome by Cai et al. (2009), it could not be detected by two recent studies using the newest large-scale data sets of human diversity (Hernandez et al. 2011; Lohmueller et al. 2011). In particular, Hernandez et al. (2011) searched for lower levels of neutral diversity near functional substitutions by contrasting levels of neutral diversity near nonsynonymous compared with synonymous substitutions. They did not find this signature in the human genome and, moreover, found that diversity might in fact be marginally higher near nonsynonymous substitutions. Simulations showed that this puts sharp limits on the amount of adaptation by classic selective sweeps in recent human evolution (Hernandez et al. 2011).However, it is likely that the study design of Hernandez et al. (2011) (also implemented in Drosophila by Sattath et al. 2011) is strongly biased against finding signatures of positive selection in the human genome and all other genomes with sharply variable levels of genomic constraint. This is because, as we show in the Results, nonsynonymous substitutions in the human genome tend to be located in regions of weaker constraint and thus weaker BGS compared with synonymous substitutions. These differences in levels of BGS should elevate neutral diversity near nonsynonymous compared with synonymous substitutions. The approach of Hernandez et al. (2011) would thus detect positive selection only if the reduction of diversity due to positive selection near nonsynonymous substitutions happens to be greater than the initial difference in the opposite direction due to BGS.Here we utilize a number of more sensitive approaches in the search for signatures of positive selection while attempting to reduce the confounding effects of BGS to the greatest extent possible. Our results suggest that positive selection was frequent in human history and might have involved adaptive mutations of substantial selective effect. We estimate that a few hundred strong adaptive events are likely to be detectable in the human genome, consistent with the latest scan for positive selection (Grossman et al. 2013). Moreover, we provide evidence that the majority of adaptive substitutions were due to cis-regulatory rather than protein-coding changes, consistent with the King and Wilson (1975) hypothesis that adaptive divergence is primarily driven by regulatory changes.     

Relationship between Habitual Intake of Vitamins and New-Onset Prediabetes/Diabetes after Acute Pancreatitis

Vitamins have many established roles in human health. However, the role of habitual dietary intake of vitamins in glucose homeostasis in individuals after acute pancreatitis (AP) is yet to be elucidated. The aim was to investigate the associations between habitual intake of fat- and water-soluble vitamins/vitamers and markers of glucose metabolism (fasting plasma glucose (FPG), homeostasis model assessment insulin resistance (HOMA-IR) index, and homeostasis model assessment β-cell function (HOMA-β)) in individuals after AP. A total of 106 participants after AP were included in this cross-sectional study and were grouped based on glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Habitual intake of seven fat-soluble vitamins/vitamers and seven water-soluble vitamins were determined by the EPIC-Norfolk food frequency questionnaire. Multiple linear regression analyses were conducted using five statistical models built to adjust for covariates (age, sex, daily energy intake, visceral/subcutaneous fat volume ratio, smoking status, daily alcohol intake, aetiology of AP, number of AP episodes, cholecystectomy, and use of antidiabetic medications). In the NODAP group, three fat-soluble vitamins/vitamers (α-carotene, β-carotene, and total carotene) were significantly associated with HOMA-β. One water-soluble vitamin (vitamin B3) was also significantly associated with HOMA-β in the NODAP group. None of the studied vitamins were significantly associated with FPG or HOMA-IR in the NODAP group. Prospective longitudinal studies and randomised controlled trials are now warranted to investigate if the observed associations between vitamin/vitamer intake and NODAP are causal and to unveil the specific mechanisms underlying their involvement with NODAP.     

One-step synthesis,characterization and properties of novel hybrid electromagnetic nanomaterials based on polydiphenylamine and Co–Fe particles in the absence and presence of single-walled carbon nanotubes

A one-step preparation method for hybrid electromagnetic nanomaterials based on polydiphenylamine (PDPA) and bimetallic Co–Fe particles in the absence and presence of single-walled carbon nanotubes (SWCNT) was proposed. During IR heating of PDPA in the presence of Co(ii) and Fe(iii) salts in an inert atmosphere at T = 450–600 °C, the polycondensation of diphenylamine (DPA) oligomers and dehydrogenation of phenyleneamine units of the polymer with the formation of C N bonds and reduction of metals by evolved hydrogen with the formation of bimetallic Co–Fe particles dispersed in a polymer matrix occur simultaneously. When carbon nanotubes are introduced into the reaction system, a nanocomposite material is formed, in which bimetallic Co–Fe particles immobilized on SWCNT are distributed in the matrix of the polymer. According to XRD data, reflection peaks of bimetallic Co–Fe particles at diffraction scattering angles 2θ = 69.04° and 106.5° correspond to a solid solution based on the fcc-Co crystal lattice. According to SEM and TEM data, a mixture of particles with sizes of 8–30 nm and 400–800 nm (Co–Fe/PDPA) and 23–50 nm and 400–1100 nm (Co–Fe/SWCNT/PDPA) is formed in the nanocomposites. The obtained multifunctional Co–Fe/PDPA and Co–Fe/SWCNT/PDPA nanomaterials demonstrate good thermal, electrical and magnetic properties. The saturation magnetization of the nanomaterials is M_S = 14.99–31.32 emu g⁻¹ (Co–Fe/PDPA) and M_S = 29.48–48.84 emu g⁻¹ (Co–Fe/SWCNT/PDPA). The electrical conductivity of the nanomaterials reaches 3.5 × 10⁻³ S cm⁻¹ (Co–Fe/PDPA) and 1.3 S cm⁻¹ (Co–Fe/SWCNT/PDPA). In an inert medium, at 1000 °C the residue is 71–77%.

In a self-organizing system within one stage under IR heating conditions, hybrid nanomaterials are formed with a structure that contains bimetallic Co–Fe particles, free or immobilized on the SWCNT surface, dispersed in the polymer PDPA matrix.