Biomarkers of pulmonary hypertension in patients with scleroderma: a case–control study

IntroductionSignificant pulmonary vascular disease is a leading cause of death in patients with scleroderma, and early detection and early medical intervention are important, as they may delay disease progression and improve survival and quality of life. Although several biomarkers have been proposed, there remains a need to define a reliable biomarker of early pulmonary vascular disease and subsequent development of pulmonary hypertension (PH). The purpose of this study was to define potential biomarkers for clinically significant pulmonary vascular disease in patients with scleroderma.MethodsThe circulating growth factors basic fibroblast growth factor, placental growth factor (PlGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor, and soluble VEGF receptor 1 (sFlt-1), as well as cytokines (interleukin [IL]-1β IL-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor-α, and interferon-γ), were quantified in patients with scleroderma with PH (n = 37) or without PH (n = 40). In non-parametric unadjusted analyses, we examined associations of growth factor and cytokine levels with PH. In a subset of each group, a second set of earlier samples, drawn 3.0±1.6 years earlier, were assessed to determine the changes over time.ResultssFlt-1 (p = 0.02) and PlGF (p = 0.02) were higher in the PH than in the non-PH group. sFlt-1 (ρ = 0.3245; p = 0.01) positively correlated with right ventricular systolic pressure. Both PlGF (p = 0.03) and sFlt-1 (p = 0.04) positively correlated with the ratio of forced vital capacity to diffusing capacity for carbon monoxide (DLCO), and both inversely correlated with DLCO (p = 0.01). Both PlGF and sFlt-1 levels were stable over time in the control population.ConclusionsOur study demonstrated clear associations between regulators of angiogenesis (sFlt-1 and PlGF) and measures of PH in scleroderma and that these growth factors are potential biomarkers for PH in patients with scleroderma. Larger longitudinal studies are required for validation of our results.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0712-4) contains supplementary material, which is available to authorized users.     

Simulations of UV–visible spectra for analytical applications: phenothiazines as a case study

Simulation of UV–vis spectra over the whole absorption window requires not only an accurate approach for the estimation of electronic transitions' energies, but also to take properly into account solvent and band-broadening effects. Although the first, solvent, can be easily introduced in quantum-chemical calculations at both implicit and explicit levels, the second, band broadening, is more troublesome to evaluate. To this end, in this contribution, we propose a protocol aimed to correctly simulate the whole absorption UV–vis spectra of organic molecules based on time-dependent density functional theory, coupled with implicit and explicit solvent models, and on the use of a fitting procedure with respect to the experimental data in order to define the best band broadening. This protocol is applied to the simulation of absorption spectra of 10H-phenothiazine and three related molecules, N,N-diphenylamine, iminodibenzyl and 10H-phenothiazine-5-oxide, which appear as impurities during its industrial synthesis. The obtained results show not only that the main peak positions are reproduced with an error not exceeding 10 nm (in the 200–400 nm range) but also that the overall shape of the UV–vis spectra can be correctly simulated.     

Interaction of the antimicrobial peptide gramicidin S with dimyristoyl–phosphatidylcholine bilayer membranes: a densitometry and sound velocimetry study

We determined changes in the volume and adiabatic compressibility of large multi- and unilamellar vesicles composed of dimyristoylphosphatidylcholine containing various concentrations of the antimicrobial peptide gramicidin S (GS) by applying densitometry and sound velocimetry. Gramicidin S incorporation was found to progressively decrease the phase transition temperature of DMPC vesicles as well as to decrease the degree of cooperativity of the main phase transition and to increase the volume compressibility of the vesicles. GS probably enhanced thermal fluctuations at the region of main phase transition and provide more freedom of rotational movement for the phospholipid hydrocarbon chains. The ability of GS to increase the membrane compressibility and to decrease the phase transition temperature is evidence for regions of distorted membrane structure around incorporated gramicidin S molecules. At relatively high GS concentration (10 mol%), more significant changes of specific volume and compressibility appear. This might suggest changes in the integrity of the lipid bilayer upon interaction with high concentrations of GS.     

Preparation of electrospun core–sheath yarn with enhanced bioproperties for biomedical materials

Objectives

To create a multifunctional medical material that combines the advantages of both nanofibers and macroyarns.

Results

A novel electrospinning-based approach was developed for creating polycaprolactone (PCL) nanofiber covered yarns (PCL-NCYs) in which polyglycolic acid multi-strand filaments (PGA-MFs) were used as the core. BALB/3T3 (mouse embryonic fibroblast cell line) cells were cultured on the PCL-NCYs substrate and cell morphology and proliferation were determined by methylthiazol tetrazolium (MTT) assay. Compared with PGA-MFs, PCL-NCYs had a higher porosity and tensile strength of 88 ± 8% and 348 ± 16 MPa and in particular, the porosity was four times higher. BALB/3T3 cells attached more easily onto the nanofiber structure and proliferated along the direction of nanofibers, indicating that PCL-NCYs can achieve better cell differentiation and proliferation.

Conclusions

PCL-NCYs can be created by combining electrospinning covering and textile twisting, and have better mechanical property and higher porosity, and can be used as a novel scaffold in tissue engineering.

     

Are nest-detection probability methods relevant for estimating turtle dove breeding populations? a case study in Moroccan agroecosystems

Knowing the population size of game is a basic prerequisite to determining adequate hunting management and conservation strategies and setting up appropriate hunting quotas. This study compared three methods complete count, capture–recapture and N-mixture modelling to estimate a turtle dove Streptopelia turtur breeding population using nest counts. We randomly sampled 143 fruit farms (60 orange orchards and 83 olive orchards) situated in an irrigated area in Morocco at the peak of breeding activity. We calculated the probability of detecting active turtle dove nests using information from two observers who independently searched the same sample plots. We found that (a) the capture–recapture method provided more precise results of nest abundance than N-mixture modelling, and that (b) the probability of nest detection was noticeably different between the two study orchards—higher in the orange orchards than in the olive orchards. Although these two methods are easy to implement and cost-effective for estimating population abundance on a large spatial scale, our results demonstrate that the resulting estimates are prone to bias depending on the tree height of the plantations. Of the three methods for estimating turtle dove abundance, complete counts were preferable for assessing population size. Using the complete counts, the density of turtle dove nests was found to be 2.96 nests/ha in the orange orchards and 0.93 nests/ha in the olive orchards. A density extrapolation to the entire surface area of the Tadla Region indicated a minimum breeding population size of 58,969 pairs (95 % confidence interval: 48,550–69,353).     

Life cycle assessment of composite packaging waste management—a Chinese case study on aseptic packaging

Purpose

Approximately 46,000 t/day of packaging waste was generated in China in 2010, of which, 2,500 t was composite packaging waste. Due to the lack of recycling technology and an imperfect recovery system, most of this waste is processed in sanitary landfills. An effective packaging waste management system is needed since this waste not only uses up valuable resources, but also increases environmental pollution. The purpose of this study is to estimate the environmental impact of the treatment scenarios in composite packaging waste which are commonly used in China, to determine the optimum composite packaging waste management strategy, and to design new separating and recycling technology for composite packaging, based on the life cycle assessment (LCA) results.

Methods

To identify the best treatment for composite packaging waste, the LCA software SimaPro 7.1.6 was used to assist in the analysis of the environmental impacts, coupled with the impact assessment method Eco-Indicator 99. LCA for composite packaging waste management was carried out by estimating the environmental impacts of the four scenarios most often used in China: landfill, incineration, paper recycling, and separation of polyethylene and aluminum. One ton of post-consumption Tetra Pak waste was selected as the functional unit. The data on the mass, energy fluxes, and environmental emissions were obtained from literature and site investigations.

Results and discussion

Landfill—scenario 1—was the worst waste management option. Paper recycling—scenario 3—was more environmentally friendly than incineration, scenario 2. Scenario 4, separating out polyethylene and aluminum, was established based on the LCA result, and inventory data were obtained from the demonstration project built by this research. In scenario 4, the demonstration project for the separation of polyethylene and aluminum was built based on the optimum conditions from single-factor and orthogonal experiments. Adding this flow process into the life cycle of composite packaging waste treatment decreased the environmental impacts significantly.

Conclusions

The research results can provide useful scientific information for policymakers in China to make decisions regarding composite packaging waste. Incineration could reduce more environmental impacts in the respiratory inorganics category, and separation of polyethylene and aluminum, in the fossil fuel category. If energy saving is the primary governmental goal, the separation of polyethylene and aluminum would be the better choice, while incineration would be the better choice for emission reduction.     

Confirming genes influencing risk to cleft lip with/without cleft palate in a case–parent trio study

A collection of 1,108 case–parent trios ascertained through an isolated, nonsyndromic cleft lip with or without cleft palate (CL/P) was used to replicate the findings from a genome-wide association study (GWAS) conducted by Beaty et al. (Nat Genet 42:525–529, 2010), where four different genes/regions were identified as influencing risk to CL/P. Tagging SNPs for 33 different genes were genotyped (1,269 SNPs). All four of the genes originally identified as showing genome-wide significance (IRF6, ABCA4 and MAF, plus the 8q24 region) were confirmed in this independent sample of trios (who were primarily of European and Southeast Asian ancestry). In addition, eight genes classified as ‘second tier’ hits in the original study (PAX7, THADA, COL8A1/FILIP1L, DCAF4L2, GADD45G, NTN1, RBFOX3 and FOXE1) showed evidence of linkage and association in this replication sample. Meta-analysis between the original GWAS trios and these replication trios showed PAX7, COL8A1/FILIP1L and NTN1 achieved genome-wide significance. Tests for gene–environment interaction between these 33 genes and maternal smoking found evidence for interaction with two additional genes: GRID2 and ELAVL2 among European mothers (who had a higher rate of smoking than Asian mothers). Formal tests for gene–gene interaction (epistasis) failed to show evidence of statistical interaction in any simple fashion. This study confirms that many different genes influence risk to CL/P.     

Application of territorial emission factors with open-access data—a territorial LCA case study of land use for livestock production in Wallonia

The International Journal of Life Cycle Assessment - This work aims to facilitate the territorial LCA applications through a case study on land use for livestock production in Wallonia (South...     

Direct electrochemical immunoassay based on a silica nanoparticles/sol–gel composite architecture for encapsulation of immunoconjugate

A highly hydrophobic and non-toxic colloidal silica nanoparticle/polyvinyl butyral sol–gel composite membrane was prepared on a platinum wire electrode. With diphtheria-toxoid (D-Ag) as a model antigen and encapsulation of diphtheria antibody (D-Ab) in the composite architecture, this membrane could be used for reagentless electrochemical immunoassay. It displayed a porous and homogeneous composite architecture without the aggregation of the immobilized protein molecules. The formation of immunoconjugate by a simple one-step immunoreaction between D-Ag in sample solution and the immobilized D-Ab introduced the change in the potential. Under optimal conditions, the D-Ag analyte could be determined in the linear ranges from 10 to 800 ng ml⁻¹ with a relatively low detection limit of 2.3 ng ml⁻¹ at 3δ. The D-Ag immunosensor exhibited good precision, high sensitivity, acceptable stability, accuracy, and reproducibility. This composite membrane could be used efficiently for the entrapment of different biomarkers and clinical applications.     

Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case–control study

Peptidylarginine deiminase type 4 (PADI4) genotypes were shown to influence susceptibility to rheumatoid arthritis (RA) in the Japanese population. Such an association could not previously be confirmed in different European populations. In the present study, we analysed exons 2–4 of PADI4 in 102 German RA patients and 102 healthy individuals to study the influence of PADI4 variability on RA susceptibility by means of haplotype-specific DNA sequencing. Analyses of the influence of PADI4 and HLA-DRB1 genotypes on disease activity and on levels of anti-cyclic citrullinated peptide antibodies were performed.     

Impact of fluorination on proteolytic stability of peptides: a case study with α-chymotrypsin and pepsin

Protease stability is a key consideration in the development of peptide-based drugs. A major approach to increase the bioavailability of pharmacologically active peptides is the incorporation of non-natural amino acids. Due to the unique properties of fluorine, fluorinated organic molecules have proven useful in the development of therapeutically active small molecules as well as in materials and crop science. This study presents data on the ability of fluorinated amino acids to influence proteolytic stability when present in peptide sequences that are based on ideal protease substrates. Different model peptides containing fluorinated amino acids or ethylglycine in the P2, P1′or P2′ positions were designed according to the specificities of the serine protease, α-chymotrypsin (EC 3.4.21.1) or the aspartic protease, pepsin (EC 3.4.23.1). The proteolytic stability of the peptides toward these enzymes was determined by an analytical RP-HPLC assay with fluorescence detection and compared to a control sequence. Molecular modeling was used to support the interpretation of the structure–activity relationship based on the analysis of potential ligand-enzyme interactions. Surprisingly, an increase in proteolytic stability was observed only in a few cases. Thus, this systematic study shows that the proteolytic stability of fluorinated peptides is not predictable, but rather is a very complex phenomenon that depends on the particular enzyme, the position of the substitution relative to the cleavage site and the fluorine content of the side chain.     

History of gonorrhea and prostate cancer in a population-based case–control study in Mexico

We evaluated the association between a history of sexually transmitted diseases (STDs) and the risk for prostate cancer (PC) among Mexican males.MethodsPC incident cases (n = 402) that were identified at six public hospitals in Mexico City were matched by age (±5 years) with 805 population controls with no history of PC. By face-to-face interview, we obtained information about sexual history, previous STDs, sociodemographic characteristics, and familial history of PC. An unconditional logistic regression model was used to estimate the risk for PC.ResultsA total of 16.6% of men reported having had at least one previous STD, and the most frequently reported STD was gonorrhea (10.5%). After adjusting by PC familial history, the history of STD was associated with a two-fold greater risk of PC: odds ratio (OR) = 2.67; 95% confidence interval (95% CI = 1.91–3.73). When each STD was evaluated separately, only gonorrhea was associated with a significant increase in PC risk (OR = 3.04; 95% CI = 1.99–4.64). These associations were similar when we stratified by low-risk PC (Gleason <7) and high-risk PC (Gleason ≥7).ConclusionThese results confirm that STDs, and particularly gonorrhea, may play an etiological role in PC among Mexican males, which is consistent with a previous report from a multiethnic cohort.     

Three gold indicators for breast cancer prognosis: a case–control study with ROC analysis for novel ratios related to CBC with (ALP and LDH)

Molecular Biology Reports - Science is still unable to develop a specific strategy for predicting breast cancer in humans. Several attempts are done to obtain the best and closest prognostic...     

Chronic tinnitus and BDNF/GDNF CpG promoter methylations: a case–control study

Brain-derived neurotrophic factor (BDNF) and Glial-derived neurotrophic factor (GDNF) are neurotrophic factors that play key roles in the auditory pathway. While the relationship between serum levels and polymorphisms of BDNF/GDNF and chronic tinnitus is emphasized in the literature, there is no study showing the link between the promoter methylations of these genes and tinnitus. For this purpose, the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations was investigated to identify their role in the pathophysiology of tinnitus. In this case–control study, we examined the possible effects of BDNF/GDNF methylations in the blood samples of patients with tinnitus complaints for more than 3 months. Sixty tinnitus subjects between the ages of 18–55 and 50 healthy control subjects in the same age group who were free of any otorhinolaryngology and systemic disease were selected for examination. Methylation of total 12 CpG sites in BDNF and GDNF promoter regions were determined by the bisulfite-pyrosequencing method. Statistically significant differences were detected between BDNF CpG6 and GDNF CpG3-5-6 methylation ratios in the comparison of control group and the chronic tinnitus patients (P?=?0.002, 0.0005, 0.00003, and 0.0029, respectively). To our knowledge, this is the first study in the literature investigating the relationship between chronic tinnitus and peripheral blood derived BDNF/GDNF promoter methylations. It is believed that the current results might be supported by investigating the relationships between BDNF/GDNF methylations and genotypes in future research using higher sample sizes.

     

Arabidopsis thaliana as a model for the study of plant–virus co-evolution

Understanding plant–virus coevolution requires wild systems in which there is no human manipulation of either host or virus. To develop such a system, we analysed virus infection in six wild populations of Arabidopsis thaliana in Central Spain. The incidence of five virus species with different life-styles was monitored during four years, and this was analysed in relation to the demography of the host populations. Total virus incidence reached 70 per cent, which suggests a role of virus infection in the population structure and dynamics of the host, under the assumption of a host fitness cost caused by the infection. Maximum incidence occurred at early growth stages, and co-infection with different viruses was frequent, two factors often resulting in increased virulence. Experimental infections under controlled conditions with two isolates of the most prevalent viruses, cauliflower mosaic virus and cucumber mosaic virus, showed that there is genetic variation for virus accumulation, although this depended on the interaction between host and virus genotypes. Comparison of Q_ST-based genetic differentiations between both host populations with F_ST genetic differentiation based on putatively neutral markers suggests different selection dynamics for resistance against different virus species or genotypes. Together, these results are compatible with a hypothesis of plant–virus coevolution.     

Association of the UCP polymorphisms with susceptibility to obesity: case–control study and meta-analysis

This paper describes a case–control study and a meta-analysis performed to evaluate if the following polymorphisms are associated with presence of obesity: ?3826A/G (UCP1); ?866G/A, Ala55Val and Ins/Del (UCP2) and ?55C/T (UCP3). The case–control study enrolled 282 obese and 483 non-obese patients with type 2 diabetes. A literature search was made to identify all studies that evaluated associations between UCP1–3 polymorphisms and obesity. In the case–control study the distributions of the UCP variants did not differ between obese and non-obese groups (P > 0.05). Forty-seven studies were eligible for the meta-analysis and the results showed that the UCP2 ?866G/A and UCP3 ?55C/T polymorphisms were associated with protection to obesity in Europeans (OR = 0.89, 95 % CI 0.82–0.97 and OR = 0.88, 95 % CI 0.80–0.97, respectively). The UCP2 Ala55 val polymorphism was associated with obesity in Asians (OR = 1.61, 95 % CI 1.13–2.30). The UCP2 Ins/Del polymorphism was associated with obesity mainly in Europeans (OR = 1.19, 95 % CI 1.00–1.42). There was no significant association of the UCP1 ?3826A/G polymorphism with obesity. In our case–control study we were not able to demonstrate any association between UCP polymorphisms and obesity in T2DM patients; however, in the meta-analysis we detected a significant association of UCP2 ?866G/A, Ins/Del, Ala55Val and UCP3 ?55C/T polymorphisms with obesity.     

Metabolites predict cardiovascular disease events in persons living with HIV: a pilot case–control study

Introduction

Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking.

Methods

Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis.

Results

Factors derived from short-chain dicarboxylacylcarnitines (SCDA) (p?=?0.08) and glutamine/valine (p?=?0.003) were elevated in CAD cases compared to controls.

Conclusion

SCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.

     

Is acetylcholinesterase a pertinent biomarker to detect exposure of pyrethroids? A study case with deltamethrin

The possibility to use acetylcholinesterase as biomarker of exposure to deltamethrin insecticide in the honeybee, Apis mellifera were considered. Joined actions of deltamethrin and pirimicarb (carbamate), alone or in association (dual treatment), were investigated on AChE activity in surviving and dead honeybees in order to test its reliability as biomarker. All treatments induced a reduction in tissue AChE activity in dead bees. In surviving bees, deltamethrin treatment induced an important increase of AChE activity that is not abolished by pirimicarb treatment. The analysis of AChE forms revealed an increase in the soluble form in surviving and dead bees and an increase of the membrane form in surviving bees. No direct effect of deltamethrin on soluble and membrane AChE was observed in vitro. The important increase in AChE activity in response to deltamethrin, not altered by pirimicarb treatment, suggests that AChE activity could represent a robust biomarker specific to deltamethrin exposure in living bees.