Propeptide big-endothelin,N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study

Context: The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF).

Objectives: We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP).

Methods: Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years).

Results: Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF.

Discussion: The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF.

Conclusions: Big-ET-1improves risk stratification in patients referred for coronary angiography.     

Riboflavin as an independent and accurate biomarker for adherence in a randomized double-blind and placebo-controlled clinical trial

Background: Medication adherence is critical for success of clinical trials.

Objective: To assess oral riboflavin is an adherence marker.

Methods: Riboflavin was incorporated into active treatment and placebo pills for a clinical trial lasting for 2 years.

Results: The accuracy (area under the receiver operating curve) of urinary riboflavin was 0.91 as a binary classifier of adherence, and was similar or better than for two active study ingredients daidzein (0.92) and genistein (0.87) (all p?<?0.0001). Decreased adherence over time was similar in the two study groups.

Conclusion: Riboflavin is an accurate and useful biomarker for study pill ingestion.     

Bacterial pili,with emphasis on Mycobacterium tuberculosis curli pili: potential biomarkers for point-of care tests and therapeutics

Context: Novel biomarkers are essential for developing rapid diagnostics and therapeutic interventions

Objective: This review aimed to highlight biomarker characterisation and assessment of unique bacterial pili.

Methods: A PubMed search for bacterial pili, diagnostics, vaccine and therapeutics was performed, with emphasis on the well characterised pili.

Results: In total, 46 papers were identified and reviewed.

Conclusion: Extensive analyses of pili enabled by advanced nanotechnology and whole genome sequencing provide evidence that they are strong biomarker candidates. Mycobacterium tuberculosis curli pili are emphasised as important epitopes for the development of much needed point-of-care diagnostics and therapeutics.     

Epidermal growth factor,growth differentiation factor-15, and survivin as novel biocompatibility markers in children on chronic dialysis

Context: Chronic dialysis results in aggravation of apoptosis and cell damage, triggered by bioincompatibility of dialysis membranes and peritoneal fluids.

Objective: The aim of study was to assess the usefulness of epidermal growth factor (EGF), growth differentiation factor (GDF)-15, and survivin as novel markers of biocompatibility in dialyzed children.

Materials and methods: Parameters were assessed by ELISA in 19 patients on hemodialysis and 22 children on peritoneal dialysis.

Results: Serum concentrations of analyzed parameters in children on chronic dialysis differed significantly from controls and depended strongly on the dialysis technique.

Conclusions: EGF, GDF-15, and survivin may serve as new biocompatibility markers in children on chronic dialysis.     

Micronuclei as a marker for medical screening of subjects continuously occupationally exposed to low doses of ionizing radiation

Context: Genotoxicity assays are widely employed in human biomonitoring studies to assess genetic damage inflicted by genotoxic agents.

Objective: Evaluation of micronuclei (MN) as a screening marker of occupational ionizing radiation (IR) exposure.

Materials and methods: Using micronucleus test, peripheral blood lymphocytes (PBL) of 402 control and exposed subjects were screened for genetic damage.

Results: The mean frequencies of micronucleus test parameters were significantly higher in exposed persons. Increase of micronucleus yield with duration of exposure (DOE) by 0.303MN/year was revealed.

Discussion and conclusion: The obtained data encourage us to consider MN as valuable markers for preventive medical screening of occupationally exposed groups.     

Association between polymorphisms in IL21 gene and risk for sepsis

Context: Sepsis is now the leading cause of death in the noncardiovascular intensive care unit (ICU).

Objective: To investigate whether polymorphisms in IL21 gene contribute to sepsis susceptibility.

Materials and methods: Three single-nucleotide polymorphisms of IL21 (rs907715, rs2055979, rs12508721) were genotyped by TaqMan assay in patients with sepsis and control subjects.

Results: Polymorphisms rs2055979 and rs12508721 in IL21 were more frequent in sepsis patients compared to general population. But allele frequency of rs907715 was not significantly different between sepsis patients and control subjects.

Conclusion: Polymorphisms in IL21 may be associated with sepsis risk.     

Effect of confounding factors on a phospho-flow assay of ribosomal S6 protein for therapeutic drug monitoring of the mTOR-inhibitor everolimus in heart transplanted patients

Context: Several assays of monitoring immune cell function have been developed to enhance therapeutic drug monitoring.

Objective: An in vitro-validated whole-blood assay of phosphorylated ribosomal protein S6 (pS6RP) was evaluated for confounders to monitor the mTOR-inhibitor everolimus (ERL).

Materials and methods: Whole blood samples from 87 heart transplant recipients were analyzed for pS6RP-expression in CD3-positive T-cells by phospho-flow analysis.

Results: ERL blood concentration, laboratory parameters, co-medications, demographic and clinical data were reviewed.

Conclusion: Evaluating the pS6RP-assay revealed that pS6RP is influenced by cyclosporine A (CsA) blood concentration, duration of ERL treatment, co-medication with thiazide diuretics and different metabolic parameters.     

Detection and analysis of endogenous polar volatile organic compounds (PVOCs) in urine for human exposome research

Background: The human exposome, defined as ‘…everything that is not the genome’, comprises all chemicals in the body interacting with life processes. The exposome drives genes x environment (GxE) interactions that can cause long-term latency and chronic diseases. The exposome constantly changes in response to external exposures and internal metabolism. Different types of compounds are found in different biological media.

Objective: Measure polar volatile organic compounds (PVOCs) excreted in urine to document endogenous metabolites and exogenous compounds from environmental exposures.

Methods: Use headspace collection and sorbent tube thermal desorption coupled with bench-top gas chromatography-mass spectrometry (GC-MS) for targeted and non-targeted approaches. Identify and categorize PVOCs that may distinguish among healthy and affected individuals.

Results: Method is successfully demonstrated to tabulate a series of 28 PVOCs detected in human urine across 120 samples from 28 human subjects. Median concentrations range from below detect to 165?ng/mL. Certain PVOCs have potential health implications.

Conclusions: Headspace collection with sorbent tubes is an effective method for documenting PVOCs in urine that are otherwise difficult to measure. This methodology can provide probative information regarding biochemical processes and adverse outcome pathways (AOPs) for toxicity testing.     

The effects of nifedipine on respiratory mechanics investigated by theend-inflation occlusion method in the rat

Context: Calcium channel blockers may theoretically exhibit relaxing effects not only on vascular smooth muscle but also on airway smooth muscle.

Objective: To investigate possible effects of nifedipine on respiratory mechanics in the rat.

Methods: Respiratory system mechanical parameters were measured by the end-inflation occlusion method in the rat in vivo before and after the intraperitoneal administration of nifedipine.

Results: We found that nifedipine affects respiratory mechanics, inducing a reduction of airway resistance and of respiratory system elastance, probably because of a relaxing action on airway and parenchimal smooth muscle cells.

Conclusion: Should these results be further confirmed by human investigations, a possible role of nifedipine in pharmacological respiratory system’s diseases treatment may be suggested.     

Fungal silver nanoparticles: synthesis,application and challenges

Purpose: This paper aims to summarize recent developments regarding the synthesis, application and challenges of fungal AgNPs. Possible methods to overcome the challenge of synthesis and reduce the toxicity of AgNPs have been discussed.

Materials and methods: This review consults and summary a large number of papers.

Results: Silver nanoparticles (AgNPs) have great potential in many areas, as they possess multiple novel characteristics. Conventional methods for AgNPs biosynthesis involve chemical agents, causing environmental toxicity and high energy consumption. Fungal bioconversion is a simple, low-cost and energy-efficient biological method, which could successfully be used for AgNPs synthesis. Fungi can produce enzymes that act as both reducing and capping agents, to form stable and shape-controlled AgNPs.

Conclusions: AgNPs have great potential in the medical and food industries, due to their antimicrobial, anticancer, anti-HIV, and catalytic activities. However, the observed in vitro and in vivo toxicity poses considerable challenges in the synthesis and application of AgNPs.     

H19 non-coding RNA in urine cells detects urothelial carcinoma: a pilot study

Context: Urothelial carcinoma (UC) is common and highly recurrent. Diagnosis and follow-up involve invasive cystoscopies.

Objective: To evaluate H19 RNA in urine cells as diagnostic tool for UC.

Materials and methods: RT-PCR analysis of urine samples from healthy volunteers and UC patients.

Results: H19 RNA was unequivocally detected in the urine of 90.5% of patients and 25.9% of controls. H19 copies were three orders of magnitude higher in patients. Receiver operating characteristic analysis showed an area under the curve of 0.933.

Conclusions: This pilot study shows that urinary cell H19 is a highly sensitive test for UC and pending verification could transform patient management.     

Prognostic value of PCT,copeptin, MR-proADM,MR-proANP and CT-proET-1 for severe acute dyspnea in the emergency department: the BIODINER study

Context: Acute dyspnea is a frequent complaint in patients attending the emergency department (ED).

Objective: To evaluate the accuracy of PCT, MR-proANP, MR-proADM, copeptin and CT-proET1 for the risk-stratification of severe acute dyspnea patients presenting to the ED.

Methods: Multicenter prospective study in adult patients with a chief complaint of acute dyspnea. Pro-hormone type biomarkers concentrations were measured on arrival. Combined primary endpoint was a poor outcome.

Results: Three hundred and ninety-four patients were included, 137 (35%) met the primary endpoint. MR-proADM was the only biomarker associated with the primary endpoint (odds ratio 1.43 [95%CI: 1.13–1.82], p?=?0.003) as were the presence of paradoxical abdominal breathing (odds ratio 2.48 [95%CI: 1.31–4.68]) or cyanosis (odds ratio 3.18 [1.46–6.89])

Conclusions: In patients with severe acute dyspnea in the ED, pro-hormone type biomarkers measurements have a low added value to clinical signs for the prediction of poor outcome.     

Soil depth shapes plant functional diversity in granite outcrops vegetation of Southwestern Australia

Background: The arid and nutrient-poor Southwestern Australia is one of the global biodiversity hotspots. Embedded in this landscape, granite outcrops are considered terrestrial insular habitats supporting habitat heterogeneity when compared to the more homogenous surrounds. Ecology of plant species and communities on granite outcrops has been addressed in numerous studies. However, functional diversity (FD) in context of the environmental heterogeneity remained unexplored.

Aims: We tested whether mesic deep-soil habitats on granite outcrops can sustain larger FD than dry shallow-soil habitats.

Methods: We calculated FD for dominant species for five single traits (leaf dry matter content, foliar δ¹³C, foliar C:N ratio, plant height and specific leaf area) and their combinations. We employed Generalized Additive Mixed Models to quantify the relationship between selected climate and soil depth variables, and FD.

Results: More benign (deep-soil) habitats supported larger FD for foliar C:N, plant height and for multiple traits than did shallow-soil habitats.

Conclusions: We suggest that: (1) functional diversification, likely aimed at avoiding intra- and interspecific competition for light and nutrients acquisition, might be the important factor in deep-soil habitats; (2) deep-soils patches on and around granite outcrops may serve as ecological microrefugia for biota associated with resource-rich environments.     

Homocysteine pre-treatment increases redox capacity in both endothelial and tumor cells

Objective: We studied the modulatory effects of homocysteine pre-treatment on the disulfide reduction capacity of tumor and endothelial cells.

Methods: Human MDA-MB-231 breast carcinoma and bovine aorta endothelial cells were pre-treated for 1–24 hours with 0.5–5 mM homocysteine or homocysteine thiolactone. After washing to eliminate any rest of homocysteine or homocysteine thiolactone, cell redox capacity was determined by using a method for measuring disulfide reduction.

Results: Homocysteine pre-treatments for 1–4 hours at a concentration of 0.5–5 mM increase the disulfide reduction capacity of both tumor and endothelial cells. This effect cannot be fully mimicked by either cysteine or homocysteine thiolactone pre-treatments of tumor cells.

Discussion: Taken together, our data suggest that homocysteine can behave as an anti-oxidant agent by increasing the anti-oxidant capacity of tumor and endothelial cells.     

Big endothelin-1 level is a useful marker for predicting the presence of isolated coronary artery ectasia

Context: Endothelin-1(ET-1) has been implicated in coronary artery disease (CAD) and may be associated with coronary artery ectasia (CAE).

Objective: To clarify the relationship between big ET-1 and isolated CAE.

Methods: We measured big ET-1 with ELISA in 216 patients (CAE, n?=?72; CAD, n?=?72; normal, n?=?72) and evaluated the link with isolated CAE.

Results: The level of plasma big ET-1 was significantly higher in patients with isolated CAE (p?<?0.001). Big ET-1 was strongly and independently associated with CAE by multivariate analysis (OR 95%CI: 1.026 (1.018–1.034), p?=?0.000).

Conclusions: Big ET-1 may be a useful predictor for the presence of isolated CAE.     

Bile: miRNA pattern and protein-based biomarkers may predict acute cellular rejection after liver transplantation

Context: Bile rather than blood depicts the local inflammation in the liver and may improve prediction and diagnosis of acute cellular rejection (ACR) after liver transplantation (OLT).

Methods: Secretome and miRNAs were analyzed during the first two weeks and on clinical suspicion of ACR in the bile of 45 OLT recipients.

Results: Levels of CD44, CXCL9, miR-122, miR-133a, miR-148a and miR-194 were significantly higher in bile of patients who developed ACR within the first 6 months after OLT and during ACR.

Conclusion: Analysis of secretome and miRNA in bile could improve our understanding of the local inflammatory process during rejection.     

Apparent survival rates of a long-lived partial migrant: the Yellow-legged Gull Larus michahellis

Capsule: In Yellow-legged Gull Larus michahellis populations from the eastern Adriatic Sea, there are considerable differences in the ratio of migratory birds and apparent survival among the colonies. Survival was dependent on age, colony and area of dispersal.

Aims: To identify the ratio of migratory birds within populations of Yellow-legged Gulls, and to compare apparent survival of gulls during migration in central and northern Europe and around the Adriatic Sea.

Methods: We analysed 15 years of resighting data of Yellow-legged Gulls using a MARK multi-state model to calculate survival rates. The effects of age, natal colony and area of dispersal were examined.

Results: Almost 60% of Adriatic Yellow-legged Gulls were migratory but the ratio varied among colonies (10.3–78.3%). Survival was dependent on age, colony and area of dispersal, with average values per group ranging between 0.599 (se 0.093) and 0.684 (se 0.084).

Conclusion: The ratio of migratory and dispersive Yellow-legged Gulls from different Adriatic colonies might be affected by both inheritance and food availability.     

Trophic strategies of Yellow-legged Gull Larus michahellis on oceanic islands surrounded by deep waters

Capsule: The diet of Yellow-legged Gulls Larus michahellis on an oceanic island, surrounded by deep waters without a wide shelf, was mainly composed of terrestrial invertebrates.

Aims: To study the trophic ecology of Yellow-legged Gulls on an island surrounded by deep waters, to quantify the importance of terrestrial prey items and their availability, and to evaluate the relative importance of nutritional values of terrestrial and marine resources.

Methods: Diet was monitored for one year. We assessed the relative contribution of the main prey items and their macronutrients through the study of pellets and faeces.

Results: Terrestrial invertebrates were the most frequently consumed prey items (frequency of occurrence (FO) 67%), followed by marine fish (Osteichthyes FO 33%). Coleoptera and Orthoptera were the most consumed terrestrial invertebrates and provided a high nutritional value. The rate of consumption of terrestrial invertebrates varied in synchrony with the breeding season, being higher in spring, indicating their potential importance for reproduction.

Conclusion: It is unusual that terrestrial invertebrates constitute a large proportion of the diet of large gulls, but they seemed to cover their trophic energy requirements during the reproductive period.     

Use of materials in nest construction by Pied Flycatchers Ficedula hypoleuca reflects localized habitat and geographical location

Capsule: Pied Flycatchers Ficedula hypoleuca use different materials to construct their nests according to local availability and geographical location.

Aims: This study tested the hypotheses that Pied Flycatcher nests were constructed from the leaves of different tree species in proportion to their occurrence within the breeding territories and that nest composition varied between geographical locations.

Methods: In Lancashire, Pied Flycatcher nests were collected from nestboxes built in locations dominated by different tree species and were deconstructed to determine which materials were used.

Results: The leaves found in nests generally reflected their availability within the locality of the territories rather than showing evidence of selective use of some leaf species. However, the use of moss was dominated by the use of one species in all but two nests. Nests from Lancashire were significantly different in composition when compared with published data for nests from north Wales and central Spain.

Conclusion: Pied Flycatchers exhibit plasticity in nest construction behaviour because they were opportunistic in their choice of most leaves as nesting materials, although they may be selective in their choice of moss.