Blood biomarkers role in acute ischemic stroke patients: higher is worse or better?

Background

Thrombolytic therapy (TT) for acute ischemic stroke (AIS) can provoke bleeding’s complication depending on the ischemic lesion (IL) dimension. Inflammation involved in the setting of acute ischaemic stroke, is associated with infarct size. We aimed to study the independent correlation and association between clinical panel of routinely identified biomarkers, including inflammatory parameters, and cerebral IL dimension and site.

Results

We evaluated eleven biomarkers in 105 unrelated patients during their hospitalization after acute stroke event. Our data indicate a significant association of: a) confluent IL size with 4th quartile of Erythrocyte Sedimentation Rate (ESR) (OR = 5.250; 95% CI, 1.002 to 27.514) and an independent correlation with sex; b) confluent IL size with 3rd quartile of fibrinogen (OR = 5.5; 95% CI, 1.027 to 29.451); c) confluent IL size with 3rd quartile of platelets (OR= 0.059; 95% CI, 0.003 to 1.175) and independent correlation with sex; d) smaller IL size (OR = 5.25; 95% CI, 1.351 to 20.396) with 3rd quartile of albumin levels and nodular and parenchimal IL size with 2nd (OR = 0.227; 95% CI, 0.053 to 0.981), 3rd (OR = 0.164; 95% CI, 0.038 to 0.711) and 4th (OR = 0.205; 95% CI, 0.048 to 0.870) quartiles albumin levels; e) smaller IL size with 3rd quartile triglycerides (TG) levels (OR = 9; 95% CI, 2.487 to 32.567) and an independent correlation with anterior location. Smaller IL size, anterior AIS turned out to be independently correlated with high serum albumin levels. Finally, high INR and PTT values were associated with worse NIHSS clinical outcomes in contrast to that observed with higher albumin level.

Conclusions

We provide evidence of routine biomarkers levels correlation with acute IL size, independently of age and sex. In addition, we highlight the importance of differentiation of biomarkers normal interval levels for further improvement not only of the clinical decision making but also in post-acute clinical outcome management.

     

Vegetation at the Limits for Vegetation: Vascular Plants, Bryophytes and Lichens in a Geothermal Field

The effects of the chemical and physical factors associated with geothermal activity on plant community structure and composition were investigated in one of the largest geothermal fields of central Italy. The study site was located in the geothermal area of Sasso Pisano – Monte Rotondo Marittimo, Southern Tuscany. The percentage cover of all vascular plant, bryophyte and lichen species was estimated within 119 circular plots of 0.25 m². For each plot the soil pH, soil temperature, slope, aspect, incident radiation, soil nitrogen and carbon contents were also quantified. Two vascular plants, Calluna vulgaris and Agrostis castellana, were found to be the most widespread species tolerating the harshest conditions in terms of low soil pH and high soil temperature. The most widespread cryptogam species was Hypnum cupressiforme. Spatially autoregressive models showed that a proportion of about 41–51% of the variance in species richness of one group of plants (vascular or cryptogamic plants) could be modelled by using three or four uncorrelated environmental factors respectively (soil temperature, soil nitrogen and soil C/N ratio and these three plus incident radiation). For the total number of species (vascular and cryptogamic plants), the variance explained by the same three uncorrelated variables was about 57%. This study evidenced a strong environmental control of community composition and species richness, in a site subjected to extreme soil values of soil pH and temperature. The dominance of vascular over cryptogamic vegetation in this geothermal site can be explained by the combined effects of geothermal stress (low soil pH and high soil temperature) with the summer drought typical of the Mediterranean climate.     

2‐D PAGE and MS analysis of proteins from formalin‐fixed,paraffin‐embedded tissues

In the past decade, encouraging results have been obtained in extraction and analysis of proteins from formalin‐fixed, paraffin‐embedded (FFPE) tissues. However, 2‐D PAGE protein maps with satisfactory proteomic information and comparability to fresh tissues have never been described to date. In the present study, we report 2‐D PAGE separation and MS identification of full‐length proteins extracted from FFPE skeletal muscle tissue. The 2‐D protein profiles obtained from FFPE tissues could be matched to those achieved from frozen tissues replicates. Up to 250 spots were clearly detected in 2‐D maps of proteins from FFPE tissue following standard mass‐compatible silver staining. Protein spots from both FFPE and frozen tissue 2‐D gels were excised, subjected to in situ hydrolysis, and identified by MS analysis. Matched spots produced matched protein identifications. Moreover, 2‐D protein maps from FFPE tissues were successfully subjected to Western immunoblotting, producing comparable results to fresh‐frozen tissues. In conclusion, this study provides evidence that, when adequately extracted, full‐length proteins from FFPE tissues might be suitable to 2‐D PAGE‐MS analysis, allowing differential proteomic studies on the vast existing archives of healthy and pathological‐fixed tissues.     

Plasma Membrane-Associated Glycohydrolases Along Differentiation of Murine Neural Stem Cells

The activities of plasma membrane associated sialidase Neu3, total β-glucosidase, CBE-sensitive β-glucosidase, non-lysosomal β-glucosyl ceramidase GBA2, β-galactosidase, β-hexosaminidase and sphingomyelinase were determined at three different stages of differentiation of murine neural stem cell cultures, corresponding to precursors, commited progenitors, and differentiated cells. Cell immunostaining for specific markers of the differentiation process, performed after 7 days in culture in presence of differentiating agents, clearly showed the presence of oligodendrocytes, astrocytes and neurons. Glial cells were the most abundant. Sialidase Neu3 after a decrease from progenitors to precursors, showed an increase parallel to the differentiation process. All the other glycosidases increased their activity along differentiation. The activity of CBE-sensitive β-glucosidase and GBA2 were very similar at the precursor stage, but CBE-sensitive β-glucosidase increased 7 times while GBA2 only two in the differentiated cells. In addition, we analysed also sphingomyelinase as enzyme specifically associated to sphingolipids. The activity of this enzyme increased from precursors to differentiated cells.     

Discovery and optimization of a potent and selective triazolopyridinone series of c-Met inhibitors

Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of a structurally diverse series of carbon-linked quinoline triazolopyridinones, which demonstrates nanomolar inhibition of c-Met kinase activity. This novel series of inhibitors exhibits favorable pharmacokinetics as well as potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver pharmacodynamic model.     

Trend of Narratives in the Age of Misinformation

Social media enabled a direct path from producer to consumer of contents changing the way users get informed, debate, and shape their worldviews. Such a disintermediation might weaken consensus on social relevant issues in favor of rumors, mistrust, or conspiracy thinking—e.g., chem-trails inducing global warming, the link between vaccines and autism, or the New World Order conspiracy. Previous studies pointed out that consumers of conspiracy-like content are likely to aggregate in homophile clusters—i.e., echo-chambers. Along this path we study, by means of a thorough quantitative analysis, how different topics are consumed inside the conspiracy echo-chamber in the Italian Facebook. Through a semi-automatic topic extraction strategy, we show that the most consumed contents semantically refer to four specific categories: environment, diet, health, and geopolitics. We find similar consumption patterns by comparing users activity (likes and comments) on posts belonging to these different semantic categories. Finally, we model users mobility across the distinct topics finding that the more a user is active, the more he is likely to span on all categories. Once inside a conspiracy narrative users tend to embrace the overall corpus.     

A Tuberculin Skin Test Survey and the Annual Risk of Mycobacterium tuberculosis Infection in Gambian School Children

Background

A Tuberculin skin test (TST) survey was conducted to assess the prevalence of latent TB Infection (LTBI) and to estimate the annual risk of M. tuberculosis infection (ARTI) in Gambian school children. The results are expected to contribute to understanding of Tuberculosis epidemiology in The Gambia.

Methods

This was a nationwide, multi-cluster survey in children aged 6–11 years. Districts, 20 of 37, were selected by probability proportional to size and schools by simple random sampling. All TST were performed using the Mantoux method. Height and weight measurements were obtained for all participants. We calculated prevalence of LTBI using cut-off points of 10mm, the mirror and mixture modelling methods.

Results

TST readings were completed 13,386 children with median age of 9 years (interquartile range [IQR] 8–10 years). Mixture analysis yielded a cut-off point of 12 mm, and LTBI prevalence of 6.9% [95%CI 6.47–7.37] and the ARTI was 0.75% [95%CI 0.60–0.91]. LTBI was associated gender and urban residence (p <0.01). Nutritional status was not associated with non-reactive TST or sizes of TST indurations. ARTI did not differ significantly by age, gender, BCG vaccination or residence.

Conclusions

This estimates for LTBI prevalence and ARTI were low but this survey provides updated data. Malnutrition did not affect estimates of LTBI and ARTI. Given the low ARTI in this survey and the overlapping distribution of indurations with mixture modelling, further surveys may require complementary tests such as interferon gamma release assays or novel diagnostic tools.