Visceral fat area and cardiometabolic risk: The Kardiovize study

BackgroundVisceral fat is associated with adiposity-based complications. Bioimpedance measurement allows estimation of visceral fat area (VFA) in an easy manner. However, a validated cut-off value for VFA by bioimpedance associated with cardiometabolic risk is lacking in European population.AimTo determine cut-off values of VFA measured via bioimpedance associated with cardiometabolic risk.MethodsRandom cross-sectional Czech population-based sample of 25–64 years old subjects. Receiver Operating Characteristic (ROC) curves were used and the area under the curve (AUC), sensitivity, and specificity were calculated. The Cardiometabolic Disease Staging System (CMDS) was used to classify cardiometabolic risk: Stage 1 – 1 or 2 metabolic syndrome (MetS) components, without impaired fasting glucose (IFG); Stage 2 – MetS or IFG; Stage 3 – MetS with IFG; Stage 4 – type 2 diabetes and/or cardiovascular disease.Results2052 participants (54.5% females, median age 49 years) were included. Median VFA (inter-quartile range) were 82.2 cm² (54.8) in men and 89.8 cm² (55.6) in women. The best VFA cut-offs associated with Stage 1 in men and women were 71 cm² (sensitivity = 0.654; specificity = 0.427) and 83 cm² (sensitivity = 0.705; specificity = 0.556) ; Stage 2: 84 cm² (sensitivity = 0.673; specificity = 0.551) and 98 cm² (sensitivity = 0.702; specificity = 0.628) ; Stage 3: 90 cm² (sensitivity = 0.886; specificity = 0.605) and 109 cm² (sensitivity = 0.755; specificity = 0.704); Stage 4: 91 cm² (sensitivity = 0.625; specificity = 0.611) and 81 cm² (sensitivity = 0.695; specificity = 0.448), respectively.ConclusionA cut-off value of VFA of 71 cm² in men and 83 cm² in women exhibited the earliest stage of cardiometabolic risk, and 90 cm² in men and 109 cm² in women showed the best performance to detect risk.     

Canonical features of human antibodies recognizing the influenza hemagglutinin trimer interface

Broadly reactive antibodies targeting the influenza A virus hemagglutinin (HA) head domain are thought to be rare and to require extensive somatic mutations or unusual structural features to achieve breadth against divergent HA subtypes. Here we describe common genetic and structural features of protective human antibodies from several individuals recognizing the trimer interface (TI) of the influenza A HA head, a recently identified site of vulnerability. We examined the sequence of TI-reactive antibodies, determined crystal structures for TI antibody–antigen complexes, and analyzed the contact residues of the antibodies on HA to discover common genetic and structural features of TI antibodies. Our data reveal that many TI antibodies are encoded by a light chain variable gene segment incorporating a shared somatic mutation. In addition, these antibodies have a shared acidic residue in the heavy chain despite originating from diverse heavy chain variable gene segments. These studies show that the TI region of influenza A HA is a major antigenic site with conserved structural features that are recognized by a common human B cell public clonotype. The canonical nature of this antibody–antigen interaction suggests that the TI epitope might serve as an important target for structure-based vaccine design.     

UR‐144 in products sold via the Internet: Identification of related compounds and characterization of pyrolysis products

The synthetic cannabinoid, UR‐144 ((1‐pentyl‐1H‐indol‐3‐yl)(2,2,3,3‐tetramethylcyclopropyl)methanone), was identified in commercial ‘legal high’ products (herbal, resin, and powder). Along with this, six related compounds were detected. The most abundant one (2.1) was identified as 4‐hydroxy‐3,3,4‐trimethyl‐1‐(1‐pentyl‐1H‐indol‐3‐yl)pentan‐1‐one, a product of the electrophilic addition of water to the cyclopropane moiety in UR‐144. Compound 2.1 was found to be undergo cyclisation which leads to the formation of two additional interconvertable compounds (2.3, tentatively identified as 1‐pentyl‐3‐(4,4,5,5‐tetramethyl‐4,5‐dihydrofuran‐2‐yl)‐1H‐indole which is stable only in absence of water and also observed as GC artifact) and 2.2, a protonated derivative of 2.3 which is formed in acidic solutions. The remaining compounds were identified as possible degradation products of the group 2 compounds (4,4,5,5‐tetramethyldihydrofuran‐2(3H)‐one and 1‐pentylindoline‐2,3‐dione) and intermediates or by‐products from the synthesis of UR‐144 ((1H‐indol‐3‐yl)(2,2,3,3‐tetramethylcyclopropyl)methanone, 1‐pentyl‐1H‐indole and 1‐(1‐pentyl‐1H‐indol‐3‐yl)hexan‐1‐one). Pyrolysis of herbal products containing the group 2 compounds or UR‐144 resulted in the formation of 3,3,4‐trimethyl‐1‐(1‐pentyl‐1H‐indol‐3‐yl)pent‐4‐en‐1‐one (3). This was confirmed by separate pyrolysis of 2.1 and UR‐144. Also, the two additional minor compounds, 1‐(1‐pentyl‐1H‐indol‐3‐yl)ethanone and 1‐(1‐pentyl‐1H‐indol‐3‐yl)propan‐1‐one, were detected. Pathways for these transformations are presented. Copyright © 2013 John Wiley & Sons, Ltd.     

Cytokine profile of the blood in mice with normal and abnormal heart rhythm

Differences in the pools of 10 cytokine were found in blood samples from the caudal vein of mice with normal and abnormal heart rhythm. Both groups were albino mice bred by us and differing from mdx albino mice by the absence of mutation in muscular dystrophin gene. Mice with normal heart rhythm had low IL-17 content and elevated concentrations of proinflammatory cytokines IL-6 and IL-1α in comparison with the normal (according to published data). In mice with bradyarrhythmias, increased blood levels of IL-10, IL-6, IL-5, IL-2, IL-1α, IL-17, IL-4, TNF-α, and granulocyte-macrophage colony-stimulating factor were detected. The relative content of IL-4 and IL-17 in the total cytokine pool increased. The lifespan of mice with bradyarrhythmias and cytokine hyperexpression was shorter by 2-3 months in comparison with mice without heart rhythm disturbances and moderate changes in the cytokine pool.