Plasma cytokines in polycythemia vera: Phenotypic correlates,prognostic relevance,and comparison with myelofibrosis

Plasma cytokine milieu is abnormal in primary myelofibrosis (PMF) and correlates with disease phenotype and prognosis. In this study, we show that several plasma cytokines are also abnormally expressed in polycythemia vera (PV; n = 65), compared to normal controls (n = 35), but with a significantly different pattern than that of PMF (n = 127). Direct phenotypic correlation in PV included levels of IL‐12 with hematocrit; IL‐1b, IL‐2, IL‐7, FGF‐b, and HGF with leukocytosis; and IFN‐α and IFN‐γ with thrombocytosis. In univariate analysis, levels of 13 cytokines (out of 30 analyzed) correlated with survival but only MIP‐1β remained significant on multivariable analysis that included the other cytokines as covariates. Increased level of MIP‐1β (P < 0.01), older age (P < 0.01), and leukocytosis (P = 0.03) maintained their association with shortened survival, on multivariable analysis. This study provides preliminary observations that warrant a larger scale study and suggests the value of plasma cytokines as prognostic biomarkers in PV. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.     

Dental caries status of Dai preschool children in Yunnan Province,China

Background

The Dai people, one of the ethnic minorities in China, have a population of 1,260,000. They have the same origin as one of the main ethnic groups of Laos and Thailand. Most of the Dai live in Yunnan province, which is located in the less-developed southwestern part of China. This study aimed to describe the oral health status of Dai preschool children in China and the factors that influence their oral health status.

Methods

An oral health survey was performed between 2011 and 2012 to select Dai five-year-old children using multi-stage stratified sampling in Yunnan. Their dental caries experience was measured using the “dmft” index, and severe caries was assessed using the “pa” index, which is modified from the “pufa” index. Oral hygiene status was assessed using the visual plaque index (VPI). A questionnaire to study the children’s socio-demographic background and oral health-related behaviours was completed by the children’s parents.

Results

A total of 833 children were examined. Their caries prevalence was 89% and 49% of the children had carious tooth with pulp involvement. The mean (SD) dmft score was 7.0 (5.3). Higher dmft scores were found among children who were girls, were currently bottle-fed, took daily sweet snacks, had higher VPI scores, and had visited a dentist within the last year.

Conclusions

The caries prevalence and experience of the five-year-old Dai children in Yunnan, China was high, and almost half had severe caries. The caries experience was associated with gender, snack habits, dental visit habits, and oral hygiene status.

     

The prognostic value of serum methotrexate area under curve in elderly primary CNS lymphoma patients

Studies on pharmacokinetics and pharmacodynamics of high-dose methotrexate chemotherapy (HD-MTX) in elderly primary central nervous system lymphoma (PCNSL) patients are rare. MTX exposure time has recently been proposed as an outcome determining factor in PCNSL. We investigated 49 immunocompetent PCNSL patients (female N=30, male N=19, median age 73 years) who were treated according to HD-MTX-based protocols. A two-compartment pharmacokinetic model was used to describe the MTX clearance. Response to treatment was assessed by MRI. We used multivariable models to investigate the association between MTX exposure and tumor response as well as survival. Dose normalized MTX peak serum levels [C (max), μmol/L g] and dose normalized area under the curve [AUC(dn), μmol h/L g] were higher in females than in males, respectively [59.4 (f) vs. 48.1 (m), P<0.001; 373.2 (f) vs. 271.9 (m), P=0.008]. Increasing AUC was inversely correlated with tumor response. AUC values above 2,126 h?μmol/L were independently associated with shorter overall and progression-free survival [hazard ratio (HR), 4.56, 95 % CI 1.74-11.94; HR 2.87, 95 % CI 1.18-7.00]. Exceedingly high MTX AUC levels can have a negative impact on progression-free and overall survivals in elderly PCNSL patients.     

The influence of structural gradients in large pore organosilica materials on the capabilities for hosting cellular communities

Cells exist in the so-called extracellular matrix (ECM) in their native state, and numerous future applications require reliable and potent ECM-mimics. A perspective, which goes beyond ECM emulation, is the design of a host-material with features which are not accessible in the biological portfolio. Such a feature would, for instance, be the creation of a structural or chemical gradient, and to explore how this special property influences the biological processes. First, we wanted to test if macroporous organosilica materials with appropriate surface modification can act as a host for the implementation of human cells like HeLa or LUHMES. It was possible to use a commercially available polymeric foam as a scaffold and coat it with a thiophenol-containing organosilica layer, followed by biofunctionalization with biotin using click chemistry and the subsequent coupling of streptavidin–fibronectin to it. More importantly, deformation of the scaffold allowed the generation of a permanent structural gradient. In this work, we show that the structural gradient has a tremendous influence on the capability of the described material for the accommodation of living cells. The introduction of a bi-directional gradient enabled the establishment of a cellular community comprising different cell types in spatially distinct regions of the material. An interesting perspective is to study communication between cell types or to create cellular communities, which can never exist in a natural environment.

Chemical and structural gradients in biofunctionalized organosilica–polymer nanocomposites control cell adhesion properties and open perspectives for artificial cellular community systems.