Correlation between measures of insulin resistance in fasting and non-fasting blood

<p>Abstract</p> <p>Background</p> <p>Epidemiological investigation of insulin resistance is difficult. Standard measures of insulin resistance require invasive investigations, which are impractical for large-scale studies. Surrogate measures using fasting blood samples have been developed, but even these are difficult to obtain in population-based studies. Measures of insulin resistance have not been validated in non-fasting blood samples. Our objective was to assess the correlations between fasting and non-fasting measures of insulin resistance/sensitivity.</p> <p>Methods</p> <p>Fasting and non-fasting measurements of metabolic function were compared in 30 volunteers (15 male) aged 28 to 48 years. Participants provided a morning blood sample after an overnight fast and a second sample approximately 4 hours after lunch on the same day.</p> <p>Results</p> <p>Non-fasting levels of the adipokines leptin, adiponectin, and leptin:adiponectin ratios were not significantly different and highly correlated with fasting values (r values 0.95, 0.96, and 0.95 respectively, P values < 0.001). There were moderate correlations between fasting and non-fasting estimates of insulin sensitivity using the McAuley (r = 0.60, P = 0.001) and QUICKI formulae (r = 0.39, P = 0.037). The HOMA-IR estimate of insulin resistance was also moderately correlated (r = 0.45, P = 0.016).</p> <p>Conclusions</p> <p>Semi-fasting measures of leptin, adiponectin, and leptin:adiponectin ratios correlate closely with fasting values and are likely to be sufficient for population-based research. Other measures of insulin resistance or sensitivity in semi-fasted blood samples are moderately correlated with values obtained after an overnight fast. These estimates of insulin resistance/sensitivity may also be adequate for many epidemiological studies and would avoid the difficulties of obtaining fasting blood samples.</p

Coulomb implosion mechanism of negative ion acceleration in laser plasmas

Coulomb implosion mechanism of the negatively charged ion acceleration in laser plasmas is proposed. When a cluster target is irradiated by an intense laser pulse and the Coulomb explosion of positively charged ions occurs, the negative ions are accelerated inward. The maximum energy of negative ions is several times lower than that of positive ions. The theoretical description and Particle-in-Cell simulation of the Coulomb implosion mechanism and the evidence of the negative ion acceleration in the experiments on the high intensity laser pulse interaction with the cluster targets are presented.Comment: 4 page

Importance of Lid Hygiene Before Ocular Surgery: Qualitative and Quantitative Analysis of Eyelid and Conjunctiva Microbiota

Objective: To evaluate the efficacy of a cleansing eyelid wipe in reducing the microbiota present on the ocular surface before cataract surgery. Methods: A single-center, prospective, single-blind phase IV study was conducted at the University Complutense of Madrid. Forty-five adult patients who were scheduled for ocular surgery after treatment with commercially available eyelid wipes were consecutively enrolled. The study lasted 5 days and the patients were examined at day 0 (D0), day 3 (D3), and day 5 (D5). They received instructions to apply the eyelid wipe only to the eye subject to surgery, using the other eye as a control with no treatment. Lid and conjunctival swabs were taken on each day and microbes identified. Ocular surface microbiota was estimated by measuring the area of the agar plate occupied by the grown colonies with respect to the total available area. Results: Measurements at D3 and D5 showed a percent reduction of 58% and 63%, respectively, in the microbial load on the eyelid in the treated eyes (P=0.0011). There was also a reduction, although nonsignificant, in the microbiota of the conjunctiva of 72% and 69% on D3 and D5, respectively. Conclusions: The degree of microbiota reduction was comparable with that obtained after topical application of antibiotics in other studies. The results suggest the use of these eyelid wipes as a complementary prophylactic method before any ocular surgery

Use of dried blood for measurement of trans fatty acids

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Genetic Deletion of a Single Immunodominant T-cell Response Confers Susceptibility to Virus-induced Demyelination

An important question in neuropathology involves determining the antigens that are targeted during demyelinating disease. Viral infection of the central nervous system (CNS) leads to T-cell responses that can be protective as well as pathogenic. In the Theiler’s murine encephalomyelitis virus (TMEV) model of demyelination it is known that the immune response to the viral capsid protein 2 (VP2) is critical for disease pathogenesis. This study shows that expressing the whole viral capsid VP2 or the minimal CD8-specific peptide VP2(121-130) as “self” leads to a loss of VP2-specific immune responses. Loss of responsiveness is caused by T cell-specific tolerance, as VP2-specific antibodies are generated in response to infection. More importantly, these mice lose the CD8 T-cell response to the immunodominant peptide VP2(121-130), which is critical for the development of demyelinating disease. The transgenic mice fail to clear the infection and develop chronic demyelinating disease in the spinal cord white matter. These findings demonstrate that T-cell responses can be removed by transgenic expression and that lack of responsiveness alters viral clearance and CNS pathology. This model will be important for understanding the mechanisms involved in antigen-specific T-cell deletion and the contribution of this response to CNS pathology

Nanobiopolymer for Direct Targeting and Inhibition of EGFR Expression in Triple Negative Breast Cancer

Treatment options for triple negative breast cancer (TNBC) are generally limited to cytotoxic chemotherapy. Recently, anti-epidermal growth factor receptor (EGFR) therapy has been introduced for TNBC patients. We engineered a novel nanobioconjugate based on a poly(β-L-malic acid) (PMLA) nanoplatform for TNBC treatment. The nanobioconjugate carries anti-tumor nucleosome-specific monoclonal antibody (mAb) 2C5 to target breast cancer cells, anti-mouse transferrin receptor (TfR) antibody for drug delivery through the host endothelial system, and Morpholino antisense oligonucleotide (AON) to inhibit EGFR synthesis. The nanobioconjugates variants were: (1) P (BioPolymer) with AON, 2C5 and anti-TfR for tumor endothelial and cancer cell targeting, and EGFR suppression (P/AON/2C5/TfR), and (2) P with AON and 2C5 (P/AON/2C5). Controls included (3) P with 2C5 but without AON (P/2C5), (4) PBS, and (5) P with PEG and leucine ester (LOEt) for endosomal escape (P/mPEG/LOEt). Drugs were injected intravenously to MDA-MB-468 TNBC bearing mice. Tissue accumulation of injected nanobioconjugates labeled with Alexa Fluor 680 was examined by Xenogen IVIS 200 (live imaging) and confocal microscopy of tissue sections. Levels of EGFR, phosphorylated and total Akt in tumor samples were detected by western blotting

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Adherence to Cancer Prevention Guidelines in 18 African Countries

Background Cancer rates in Africa are projected to double by 2030 due to aging and increased exposure to cancer risk factors, including modifiable risk factors. We assessed adherence to 5 modifiable cancer risk factors across 18 African countries. Methods Data on adults 18 years and older were obtained from the 2002–2004 World Health Survey. Adherence to current World Cancer Research Fund guidelines on smoking, alcohol, body weight, physical activity, and nutrition was assessed. Adherence scores ranged from 0 (no guideline met) to 5 (all guidelines met). Determinants of adherence were assessed using multivariable linear regression adjusted for individual and country level characteristics. Results Across all countries, adherence to the guidelines among adults was high for smoking (72%–99%) and alcohol (85%–100%), but low for body weight (1.8%–78%), physical activity (3.4%–84%) and nutrition (1.4%–61%). Overall adherence score ranged from 2.32 in Mali to 3.72 in Comoros. In multivariable models, residing in low versus high SES households was associated with reduced adherence by 0.24 and 0.21 points for men and women respectively after adjusting for age, gender, education, and marital status (p<0.001). Every % increase in GDP spent on health was associated with increased adherence by 0.03 in men and 0.09 in women (p<0.001). Conclusions The wide variation in adherence to cancer prevention guidelines observed across countries and between population sub-groups suggests the need for targeted public health efforts to improve behaviors related to body weight, physical activity and nutrition

Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization