Non-Steroidal Anti-Inflammatory Drugs Use Is Associated with Reduced Risk of Inflammation-Associated Cancers: NIH-AARP Study

Background

Chronic inflammation has been linked to cancers, and use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of several cancers. To further refine the magnitude of NSAID-related associations, in particular for cancers related to inflammation, such as alcohol-, infection-, obesity-, and smoking-related cancers, as well as for less common cancers, we evaluated the use of NSAIDs and cancer risk in a very large cohort. We used propensity scores to account for potential selection bias and hypothesized that NSAID use is associated with decreased cancer incidence.

Methods

We conducted a prospective study among 314,522 participants in the NIH-AARP Diet and Health Study. Individuals who completed the lifestyle questionnaire, which included NSAID use, in 1996–1997 were followed through 2006. Information on cancer incidence was ascertained by linking to cancer registries and vital status databases.

Findings

During 2,715,994 person-years of follow-up (median 10.1 person-years), there were 51,894 incident cancers. Compared with non-users of NSAIDs, individuals who reported use in the 12 months prior to interview had a significantly lower risk of all inflammation-related cancer, alcohol-related, infection-related, obesity-related, and smoking-related cancers [hazard ratio (HR) (95% CI)) 0.90 (0.87–0.93), 0.80 (0.74–0.85), 0.82 (0.78–0.87), 0.88 (0.84–0.92), and 0.88 (0.85–0.92) respectively)].

Conclusions

After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.     

Development of a measles vaccine production process in MRC-5 cells grown on Cytodex1 microcarriers and in a stirred bioreactor

Measles vaccination remains the most efficient way to control the spread of the virus. This work focuses on the production of a measles vaccine using stirred conditions as an advanced option for process scale up. Non-porous Cytodex 1 microcarriers were used to support MRC-5 cell growth in suspension cultures. Virus replication was first optimized in spinner flasks, and the effects of various operational parameters were investigated. Cell infection with AIK-C measles strain at an MOI (multiplicity of infection) of 0.005, without glucose regulation and in M199 medium, resulted in a virus titer of 10^6.25 TCID₅₀ (median tissue culture infective dose)/ml. To optimize the production process in a 7-l bioreactor, we carried out various perfused cultures using minimum essential medium (MEM) + 5% FCS diluted with phosphate-buffered saline (PBS). We achieved a high cell density level (4.1 × 10⁶ cells/ml) with an efficient use of the medium when MEM + 5% FCS diluted with PBS at 25% was used during the cell amplification step. Optimization of measles production in MRC-5 cells grown on Cytodex 1 beads in a 7-l bioreactor showed that perfusion was the most efficient when compared to repeated-batch culture. Perfusion at a rate of 0.25 V (reactor volume)/day showed the highest specific productivity (1.6 IVP [infectious virus particle] cell⁻¹ day⁻¹). Testing of several stabilizers containing pharmaceutically improved components such as sugars, amino acids, and charged ions showed that the formulation composed of sucrose and MgCl₂, led to the maintenance of the infectivity of the AIK-C measles virus strain to a significant level, when stored at +28 °C, +4 °C and −60 °C.     

Caryological study on four Hesperis L. (Cruciferae) taxa from the Diaplictos (Dvorák) Dvorák section in Turkey

This study examined chromosome numbers and karyotypes of four taxa, Hesperis novakii Dvorák, H. bottae Fourn., H. balansae Fourn. and H. syriaca (DC.) Dvorák, from naturally growing Diaplictos (Dvorák) Dvorák section, which is represented by only these four taxa in Turkey, in the genus Hesperis. H. novakii and H. syriaca have 2n=14 chromosomes, H. bottae and H. balansae have 2n=12 chromosomes in somatic cells. Total chromosome lengths are 5.37 mum and 2.17 mum in H. novakii, 5.38 mum and 2.70 mum in H. bottae, 9.59 mum and 4.28 mum in H. balansae, 4.88 mum and 2.32 mum in H. syriaca (no. 4969), 7.89 mum and 3.44 mum in H. syriaca (no. 4971). The karyotypes are as follows: H. novakii consists of 3m+1sm+1st+2T, H. bottae consists of 4m+2st, H. balansae consists of 4m+2sm, H. syriaca (no. 4969) consists of 3m+1sm+1st+2T and H. syriaca (no. 4971) consists of 3m+1sm+1st+2T chromosome pairs. Results were discussed from a cytological and taxonomical point of view.     

Pollen morphology of Lathyrus (Fabaceae) taxa in the Platystylis section from Turkey

In this study, the pollen morphology of 18 wild taxa of Lathyrus L. grown in Turkey: L. pallescens (Bieb.) Koch, L. brachypterus Cel., L. haussknechtii Sirj., L. karsianus P. H. Davis, L. satdaghensis P. H. Davis, L. nivalis Hand.-Mazz, L. atropatanus (Grossh.) Sir., L. armenus (Boiss. and Huet) Sirj., L. cyaneus (Stev.) Koch var. cyaneus, L. cyaneus var. pinnatus?Davis, L. digitatus (Bieb.) Fiori, L. tukhtensis Czecz., L. variabilis (Boiss. and Ky.) Maly, L. spathulatus Cel. L. elongatus (Bornm.) Sirj., L. cilicicus Hayek and Siehe, L. boissieri Sirj., and L. bitlisicus Pe?men was examined by light microscopy and scanning electron microscopy. The pollen grains were 3-zonocolporate, of spheroidal-subprolate-prolate (P/E?=?0.957?C1.252) types, and medium in size. Equatorial view: rectangular or elliptical-obtuse-convex, polar view: circular, triangular or quinquangular-obtuse-convex. The smallest pollen grains belonged to L. elongatus (P?=?36.972/E?=?38.636) and the largest to L. cyaneus var. cyaneus (P?=?46.332/E?=?32.864). The ornamentation was perforate-foveolate or slightly reticulate. Some photographs included in this work were taken using both light microscopy and scanning electron microscopy.     

A Review Molecular Typing Methods for <Emphasis Type="Italic">Aspergillus flavus</Emphasis> Isolates

Aspergillus flavus is the second most important Aspergillus species causing human infections. The importance of this fungus increases in regions with a dry and hot climate. Small phylogenetic studies in Aspergillus flavus indicate that the morphological species contains several genetically isolated species. Different genotyping methods have been developed and employed in order to better understand the genetic and epidemiological relationships between environmental and clinical isolates. Understanding pathogen distribution and relatedness is essential for determining the epidemiology of nosocomial infections and aiding in the design of rational pathogen control methods. Typing techniques can also give us a deeper understanding of the colonization pattern in patients. Most of these studies focused on Aspergillus fumigatus because it is medically the most isolated species. To date, there has not been any publication exclusively reviewing the molecular typing techniques for Aspergillus flavus in the literature. This article reviews all these different available methods for this organism.     

Patient-specific finite-element analyses of the proximal femur with orthotropic material properties validated by experiments

Patient-specific high order finite-element (FE) models of human femurs based on quantitative computer tomography (QCT) with inhomogeneous orthotropic and isotropic material properties are addressed. The point-wise orthotropic properties are determined by a micromechanics (MM) based approach in conjunction with experimental observations at the osteon level, and two methods for determining the material trajectories are proposed (along organs outer surface, or along principal strains). QCT scans on four fresh-frozen human femurs were performed and high-order FE models were generated with either inhomogeneous MM-based orthotropic or empirically determined isotropic properties. In vitro experiments were conducted on the femurs by applying a simple stance position load on their head, recording strains on femurs' surface and head's displacements. After verifying the FE linear elastic analyses that mimic the experimental setting for numerical accuracy, we compared the FE results to the experimental observations to identify the influence of material properties on models' predictions. The strains and displacements computed by FE models having MM-based inhomogeneous orthotropic properties match the FE-results having empirically based isotropic properties well, and both are in close agreement with the experimental results. When only the strains in the femoral neck are being compared a more pronounced difference is noticed between the isotropic and orthotropic FE result. These results lay the foundation for applying more realistic inhomogeneous orthotropic material properties in FEA of femurs.     

Effect of on-field inoculation of Phaseolus vulgaris with rhizobia on soil bacterial communities

The aim of this study was to assess the impact of inoculation of Phaseolus vulgaris with two indigenous rhizobia strains on plant growth promotion, nitrogen turnover processes, richness and structure of the Rhizobiaceae and total bacterial communities in the bulk soil. Both strains used induced a significant increase in nodulation and grain yield. Analysis of bulk soil fertility showed positive, negative and strain-dependent effects of inoculation on nitrate, phosphorus and ammonium, respectively. Terminal-restriction fragment length polymorphism profiling demonstrated that inoculation significantly increased the phylotype richness of the bacterial communities. No significant difference in richness between the strains used and no additive effect of co-inoculation were observed. However, differences between both inoculants and a clear additive effect of co-inoculation on heterogeneity were found. This work gives original insights into the effect of rhizobial inoculation outside the restricted rhizospheric area. Effects on bacterial structure and diversity are clearly sensed in the neighbourhood of 25 cm and in a limited time course. Both Alpha- and Gammaproteobacteria, together with Firmicutes and Actinobacteria, were enhanced by inoculation, No evidence of terminal-restriction fragment inhibition was found. However, it remains to be answered how the impact on taxonomic groups can be related to effects on functional capabilities of soil microbial communities.     

The native-like conformation of Ure2p in fibrils assembled under physiologically relevant conditions switches to an amyloid-like conformation upon heat-treatment of the fibrils

The [URE3] phenotype in the yeast Saccharomyces cerevisiae is inherited by a prion mechanism involving self-propagating Ure2p aggregates. It is believed that assembly of intact Ure2p into fibrillar polymers that bind Congo Red and show yellow-green birefringence upon staining and are resistant to proteolysis is the consequence of a major change in the conformation of the protein. We recently dissected the assembly process of Ure2p and showed the protein to retain its native alpha-helical structure upon assembly into protein fibrils that are similar to amyloids in that they are straight, bind Congo red and show green-yellow birefringence and have an increased resistance to proteolysis (). Here we further show using specific ligand binding, FTIR spectroscopy and X-ray fiber diffraction that Ure2p fibrils assembled under physiologically relevant conditions are devoid of a cross-beta core. The X-ray fiber diffraction pattern of these fibrils reveals their well-defined axial supramolecular order. By analyzing the effect of heat-treatment on Ure2p fibrils we bring evidences for a large conformational change that occurs within the fibrils with the loss of the ligand binding capacity, decrease of the alpha helicity, the formation of a cross-beta core and the disappearance of the axial supramolecular order. The extent of the conformational change suggests that it is not limited to the N-terminal part of Ure2p polypeptide chain. We show that the heat-treated fibrils that possess a cross-beta core are unable to propagate their structural characteristic while native-like fibrils are. Finally, the potential evolution of native-like fibrils into amyloid fibrils is discussed.