Circulating Endothelial Progenitor Cells and the Risk of Vascular Events after Ischemic Stroke

Background and Purpose

We evaluated the hypothesis that the number of circulating EPC could be associated with the risk of stroke recurrence (SR) or vascular events (VE) after an ischemic stroke.

Methods

We studied prospectively consecutive patients with cerebral infarction within the first 48 hours after the onset. We recorded demographic factors, vascular risk factors, previous Rankin scale (RS) score, and etiology. We analyzed EPC counts by flow cytometry in blood collected at day 7 and defined EPC as CD34+/CD133+/KDR+ cells. Mean follow-up was 29.3 ± 16 months. We evaluated SR as well as VE. Patients were classified as to the presence or absence of EPC in the circulation (either EPC+ or EPC-). Bivariate analyses, Kaplan-Meier survival curves and Cox regression models were used.

Results

We included 121 patients (mean age 70.1±12.6 years; 65% were men). The percentage of EPC+ patients was 47.1%. SR occurred in 12 (9.9%) and VE in 18 (14.9%) patients. SR was associated significantly with a worse prior RS score, previous stroke and etiology, but not with EPC count. VE were associated significantly with EPC-, worse prior RS score, previous stroke, high age, peripheral artery disease and etiology. Cox regression model showed that EPC- (HR 7.07, p=0.003), age (HR 1.08, p=0.004) and a worse prior RS score (HR 5.8, p=0.004) were associated significantly with an increased risk of VE.

Conclusions

The absence of circulating EPC is not associated with the risk of stroke recurrence, but is associated with an increased risk of future vascular events.     

Continuous nitrous oxide abatement in a novel denitrifying off-gas bioscrubber

The potential of a bioscrubber composed of a packed bed absorption column coupled to a stirred tank denitrification bioreactor (STR) was assessed for 95 days for the continuous abatement of a diluted air emission of N₂O at different liquid recycling velocities. N₂O removal efficiencies of up to 40?±?1 % were achieved at the highest recirculation velocity (8 m h^?1) at an empty bed residence time of 3 min using a synthetic air emission containing N₂O at 104?±?12 ppm_v. N₂O was absorbed in the packed bed column and further reduced in the STR at efficiencies >80 % using methanol as electron donor. The long-term operation of the bioscrubber suggested that the specialized N₂O degrading community established was not able to use N₂O as nitrogen source. Additional nitrification assays showed that the activated sludge used as inoculum was not capable of aerobically oxidizing N₂O to nitrate or nitrite, regardless of the inorganic carbon concentration tested. Denitrification assays confirmed the ability of non-acclimated activated sludge to readily denitrify N₂O at a specific rate of 3.9 mg N₂O g VSS h^-1 using methanol as electron donor. This study constitutes, to the best of our knowledge, the first systematic assessment of the continuous abatement of N₂O in air emission. A characterization of the structure of the microbial population in the absorption column by DGGE-sequencing revealed a high microbial diversity and the presence of heterotrophic denitrifying methylotrophs.     

The Fat from Frozen Mammals Reveals Sources of Essential Fatty Acids Suitable for Palaeolithic and Neolithic Humans

The elucidation of the sources of n-3 fatty acids available for the humans in the Upper Palaeolithic and Neolithic is highly relevant in order to ascertain the availability of such nutrients in that time frame as well as to draw useful conclusions about healthy dietary habits for present-day humans. To this end, we have analysed fat from several frozen mammals found in the permafrost of Siberia (Russia). A total of 6 specimens were included in this study: 2 mammoths, i.e. baby female calf called “Lyuba” and a juvenile female called “Yuka”, both specimens approximately from the same time, i.e. Karginian Interstadial (41,000 and 34,000 years BP); two adult horses from the middle Holocene (4,600 and 4,400 years BP); and two bison very close to the Early Holocene (8,200 and 9,300 years BP). All samples were analysed by gas-liquid chromatography-mass spectrometry (GLC-MS) and GLC-flame ionization detector (GLC-FID). As demonstrated in this work, the fat of single-stomached mammals often consumed by Palaeolithic/Neolithic hunters contained suitable amounts of n-3 and n-6 fatty acids, possibly in quantities sufficient to meet the today''s recommended daily intake for good health. Moreover, the results also suggest that mammoths and horses at that time were hibernators.     

Agrin and Perlecan Mediate Tumorigenic Processes in Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels.     

A combination of physiological and chemometrics analyses reveals the main associations between quality and ripening traits and volatiles in two loquat cultivars

A combined analysis of physiological traits, volatile composition and sensory evaluation of aromatic quality was conducted on the ‘Algerie’ and ‘Golden Nuggett’ cultivars at six maturity stages, covering colour breaking to complete ripening. The main difference between cultivars during ripening was aromatic character; organoleptic differences between cultivars were assessed by a taste panel and could be explained by the volatile profile at harvest, and more specifically by those volatiles showing a rapid increase as fruits fully ripened. Among the 121 volatile compounds identified in loquat fruits, 2-methyl butanoic acid was the only cultivar-specific VOC, detected only in ‘Algerie’, while the levels of other common VOCs also contributed to differentiation between cultivars. A correlation analysis ran between volatile compounds levels and loquat aroma and flavour intensity revealed that 1,2-dimethoxy-4-(2-methoxyethenyl)benzene, elemicin, (Z)-2-hexen-1-ol, methyl 2-methylbutanoate, methyl 3,4,5-trimethoxybenzoate, cis-geranylacetone, (E)-methyl cinnamate, (E)-2-decenal, cis-edulan and 1-hydroxycyclohexyl phenyl ketone were volatiles which could importantly contribute to loquat’s aromatic character, some of which are reported here for the first time as key volatiles in aromatic quality. The correlations among the physiological parameters, the volatile compounds and physiological traits, and the parallelisms between precursors and volatile product, are discussed as they offer clues about loquat quality-associated metabolic changes during ripening.     

Influence of genetic polymorphisms in glutathione-S-transferases gene in response to imatinib among Brazilian patients with chronic myeloid leukemia

Polymorphism in metabolizing enzymes can influence drug response as well as the risk for adverse drug reactions. Nevertheless, there are still few studies analyzing the consequence of polymorphisms for the Glutathione-S-transferases (GST) gene to drug response in chronic myeloid leukemia (CML). This study reports, the influence of GSTP1*B and GSTT1/GSTM1null polymorphisms in response to imatinib in CML patients in a Brazilian population. One hundred thirty-nine CML patients from the Clinical Hospital of Goiânia, Goiás, Brazil, treated with imatinib were enrolled in this study. Genotyping of GSTT1 and GSTM1 genes deletions were performed by qPCR and of GSTP1 gene was performed by RFLP-PCR. The frequency of GSTP1*1B, GSTT1 and GSTM1null polymorphisms were determined for all patients. The influence of each patient’s genotypes was analyzed with the patient’s response to imatinib treatment. Brazilian CML patients revealed GSTT1 and GSTM1 genes deletions. GSTT1 deletion was found in 19.3% of patients and GSTM1 deletion in 48.7% of patients with CML. GSTT1/GSTM1 deletion was found in 11.7% in Brazilian CML patients. The “G allele” of GSTP1*B, is associated with later cytogenetic response in imatinib therapy. While, the gene presence combined with GG genotype (GSTM1 present/GSTPI-GG) conferred a tend to a later cytogenetic response to patients. GSTP1*B and GSTT1/GSTM1null polymorphisms influence treatment response in CML. Brazilian CML patients presenting GSTP1 AA/AG genotypes alone and in combination with GSTT1 null reach the cytogenetic response faster, while patients presenting GSTP1-GG and GSTMI positive genotypes may take longer to achieve cytogenetic response. As a result, it allows a better prognosis, with the use of an alternative therapy, other than reducing treatment cost.

     

Trophallaxis and prophylaxis: social immunity in the carpenter ant Camponotus pennsylvanicus

In social insects, group behaviour can increase disease resistance among nest-mates and generate social prophylaxis. Stomodeal trophallaxis, or mutual feeding through regurgitation, may boost colony-level immunocompetence. We provide evidence for increased trophallactic behaviour among immunized workers of the carpenter ant Camponotus pennsylvanicus, which, together with increased antimicrobial activity of the regurgitate droplet, help explain the improved survival of droplet recipient ants relative to controls following an immune challenge. We have identified a protein related to cathepsin D, a lysosomal protease, as a potential contributor to the antimicrobial activity. The combined behavioural and immunological responses to infection in these ants probably represent an effective mechanism underlying the social facilitation of disease resistance, which could potentially produce socially mediated colony-wide prophylaxis. The externalization and sharing of an individual''s immune responses via trophallaxis could be an important component of social immunity, allowing insect colonies to thrive under high pathogenic pressures.     

Dengue virus tropism in humanized mice recapitulates human dengue fever

Animal models of dengue virus disease have been very difficult to develop because of the virus' specificity for infection and replication in certain human cells. We developed a model of dengue fever in immunodeficient mice transplanted with human stem cells from umbilical cord blood. These mice show measurable signs of dengue disease as in humans (fever, viremia, erythema and thrombocytopenia), and after infection with the most virulent strain of dengue serotype 2, humanized mice showed infection in human cells in bone marrow, spleen and blood. Cytokines and chemokines were secreted by these human cells into the mouse bloodstream. We demonstrated that the pathology of dengue virus infection in these mice follows that reported in human patients, making this the first valid and relevant model for studying dengue fever pathogenesis in humans.