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.     

Nickel exposure and plasma levels of biomarkers for assessing oxidative stress in nickel electroplating workers

Context: The mechanism of nickel-induced pathogenesis remains elusive.

Objective: To examine effects of nickel exposure on plasma oxidative and anti-oxidative biomarkers.

Materials and methods: Biomarker data were collected from 154 workers with various levels of nickel exposure and from 73 controls. Correlations between nickel exposure and oxidative and anti-oxidative biomarkers were determined using linear regression models.

Results: Workers with a exposure to high nickel levels had significantly lower levels of anti-oxidants (glutathione and catalase) than those with a lower exposure to nickel; however, only glutathione showed an independent association after multivariable adjustment.

Discussion and conclusion: Exposure to high levels of nickel may reduce serum anti-oxidative capacity.     

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.     

Mutation in the beta3 subunit of Guanine nucleotide-binding protein (GNB3) gene is not associated with Type II diabetes mellitus risk: a case–control study of a North Indian population

Context: Genetics play a major role in development and pathophysiology of Type 2 diabetes mellitus (T2DM).

Objective: To asses the association of Guanine nucleotide-binding protein (GNB3) (C825T) gene's polymorphism with T2DM.

Materials and methods: A case–control study including 400 North Indians was performed using Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP) approach to analyze genetic polymorphism.

Results: No significant difference was observed in genotype and allele frequencies of GNB3 gene on comparing cases with controls.

Discussion: Our study is in agreement with studies on Polish, Japanese, Hispanic-American and Danish populations who observed no significant association between GNB3 (C825T) polymorphism and T2DM.

Conclusion: GNB3 (C825T) polymorphism is not associated with T2DM.     

MicroRNAs as possible biomarkers for screening of aortic aneurysms: a systematic review and validation study

Context: There is an urgent need to identify non-invasive biomarkers for the early detection of aortic aneurysms, preceding a fatal event. The potential role for MicroRNAs (miRNAs) as diagnostic markers for aortic aneurysms was investigated through the present systematic review.

Objective: To perform a comprehensive review on published studies examining the association of miRNAs with aortic aneurysms and further validate these results with plasma samples collected from thoracic aortic aneurysm (TAA) patients.

Methods: The literature search was performed via numerous databases and articles were only included if they fulfilled the predefined eligibility criteria. The miRNAs reported three times or more with expression consistency were validated using plasma samples from TAA patients collected before and following surgery.

Results: Twenty-four articles were selected from the literature search and 11 miRNAs were chosen for validation using our samples. The miRNAs which were further validated were found to follow the trend in the regulation pattern as with the majority of the published data. MiRNA hsa-miR-193a-5p was found to be significantly down-regulated in the plasma samples collected before the aneurysmal removal when compared with postsurgical serum samples.

Conclusions: Numerous miRNAs have been associated with aortic aneurysms, and specifically hsa-miR-193a-5p and hsa-miR-30b-5p; therefore they warrant further investigation as potential biomarkers.

Registration: The protocol of the review was registered in Prospero Databases (ID: CRD42016039953)     

Differential expression of circulating vascular cell adhesion molecule-1 in subjects with coronary artery disease and cardiac syndrome X without known diabetes mellitus

Context: Inflammation is one of the mechanisms underlying cardiac syndrome X (CSX).

Objectives: Few studies have compared the expression of inflammatory or adhesion molecules between coronary artery disease (CAD) versus CSX.

Materials and methods: Ninety-two CSX and 145 CAD subjects without known diabetes mellitus underwent coronary angiogram for angina.

Results: Vascular cell adhesion molecule (VCAM)-1 (median, 507 versus 431?ng/ml, p?=?0.001) was significantly higher in the CAD group. In the binary regression, VCAM-1 was a significant differential factor for CAD versus CSX.

Discussion and conclusion: Adhesion molecules might be implicated in the differential expression of macro versus microvascular coronary disease.

Trial registration number: NCT01198730 at https://clinicaltrials.gov     

Sleep-disordered breathing is associated with higher carboxymethyllysine level in elderly women but not elderly men in the cardiovascular health study

Context: Carboxymethyl-lysine (CML) results from oxidative stress and has been linked to cardiovascular disease.

Objective: The objective of this study is to investigate the association between sleep-disordered breathing (SDB) – a source of oxidative stress – and CML.

Materials and methods: About 1002 participants in the Cardiovascular Health Study (CHS) were studied.

Results: Women with SDB had significantly higher CML concentration compared with those without SDB (OR?=?1.63, 95%CI?=?1.03–2.58, p?=?0.04). The association was not significant among men.

Discussion: SDB was associated with CML concentration among elderly women but not men in the Cardiovascular Health Study.

Conclusion: Accumulation of CML may be an adverse health consequence of SDB     

Release kinetics of high-sensitivity cardiac troponins I and T and troponin T upstream open reading frame peptide (TnTuORF) in clinically induced acute myocardial infarction

Context: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes.

Objective: The study examined the early release kinetics of TnTuORF.

Materials and methods: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n?=?31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH).

Results: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18?ng/L versus 27?ng/L; cTnI median: 15?ng/L versus 25?ng/L). TnTuORF showed no variation.

Discussion: We observed a significantly greater increase in cTnI compared with cTnT.

Conclusion: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting.     

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.     

Circulating levels of apoptotic markers and oxidative stress parameters in women with polycystic ovary syndrome: a case-controlled descriptive study

Context: Apoptotic dysregulation plays a role in the pathogenesis of polycystic ovary syndrome (PCOS).

Objective: To evaluate circulatory apoptotic markers and oxidative stress in patients with PCOS.

Materials and methods: Forty-four women with PCOS, and 44 healthy women as controls were enrolled in the study. Oxidative stress parameters and caspases levels were measured in serum.

Results: The caspase 9 level was significantly lower and related with oxidant status in patients with PCOS, while the circulating levels of caspases 3 and 7 were statistically similar in both groups.

Discussion: This study is the first report demonstrating the circulating levels of apoptotic markers and their relationship with oxidant status in PCOS.

Conclusion: The circulating caspase 9 and oxidant status might contribute to apoptotic dysregulation in PCOS.     

Pre-fledging survival in a Yellow-legged Gull Larus michahellis population in northern Iberia is mostly determined by hatching date

Capsule: Pre-fledging survival in a Yellow-legged Gull Larus michahellis population in northern Iberia is negatively correlated to hatching date.

Aims: To explore which factors have more importance in determining the pre-fledging daily survival rates in a Yellow-legged Gull population from northern Iberia. Specifically, we tested for the effect of hatching date and order, body size and condition and meteorological conditions on pre-fledging survival.

Methods: Cormack–Jolly–Seber models with mixtures were used to model daily survival rates.

Results: Daily survival rates were mostly negatively affected by hatching date.

Conclusions: Hatching date was the most important factor affecting survival of chicks during the pre-fledging period in a Yellow-legged Gull colony from northern Iberia.     

Matrix metalloproteinase multiplex screening identifies increased MMP-2 urine concentrations in women predicted to develop preeclampsia

Background: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia.

Objective: The objective of this study is to evaluate the usefulness of nine urinary metalloproteinases to predict the risk of preeclampsia development.

Methods: MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12 and MMP-13 were analyzed in urine (early-pregnancy) from 17 women predicted to develop preeclampsia and 48 controls using the Bio-Plex Pro-Human MMP panel (Bio-Rad, Hercules, CA).

Results: Urinary MMP-2 showed differences between groups which allowed us to calculate an increased risk for PE development of up to 20 times among the study population.

Conclusion: Increased urinary concentration of MMP-2 at 12 and 16 weeks of gestation predicted an increased risk of developing preeclampsia in the study population.     

Dynamic variation of histone H3 trimethyl Lys4 (H3K4me3) and heterochromatin protein 1 (HP1) with employment length in nickel smelting workers

Objective: To investigate the dynamic variation in H3K4me3 and HP1 with employment length in nickel smelting workers.

Methods: Blood samples were collected from 140 nickel smelting workers and 140 age-matched office workers to test for H3K4me3, and HP1 levels.

Results: H3K4me3 was statistically significantly different (p?<?0.05) between the two groups and positively correlated with employment length (r_s?=_?0.267). HP1 was not correlated with employment length (p?=?0.066) but was significantly different between the two groups.

Conclusions: Chronic exposure to nickel can induce oxidative damage, and increase H3K4me3 expression and inhibit HP1 expression.     

CRP velocity and short-term mortality in ST segment elevation myocardial infarction

Context: There is a known association between C-reactive protein (CRP) levels and adverse outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). The optimal time frame to measure CRP for risk stratification is not known.

Objective: The aim of the current study was to evaluate the relation between the change in CRP velocity (CRPv) and 30-d mortality among STEMI patients.

Material and methods: We included consecutive patients with a diagnosis of STEMI who presented to Tel-Aviv Medical Center between 2008 and 2014 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24?h after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements.

Results: The study population comprised of 492 patients, mean age was 62?±?14, 80% were male. CRPv was significantly higher among patients who died within 30 d of admission (1.42?mg/l versus 0.18?mg/l, p?<?0.001). In a multivariate regression model adjusted to multiple confounders, CRPv was independently associated with 30-d mortality (OR 1.39, 95% CI: 1.20–1.62, p?<?0.001).

Conclusion: CRPv might be an independent and rapidly measurable biomarker for short-term mortality in patients presenting with STEMI.     

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.     

Prognostic significance of insulin-like growth factor-I serum levels in acute decompensation of cirrhosis

Context: IGF-I serum levels are suppressed in cirrhosis, but its prognostic significance is unknown.

Objectives: To investigate the prognostic value of IGF-I in patients admitted for acute decompensation of cirrhosis.

Materials and methods: Cohort study that included 103 patients. IGF-I was measured by enzyme-linked immunosorbent assay (ELISA).

Results: Ninety-day mortality was 26.2% and it was independently associated with MELD, age and IGF-I. The Kaplan–Meier survival probability at 90 days was 94.3% in patients with IGF-I?≥13?ng/mL and 63.2% for patients with IGF-I?<13?ng/mL (p?=?.001).

Discussion and conclusion: IGF-I levels are independently associated with mortality in acute decompensation of cirrhosis.     

Association of IL-10 (-819T/C, -592A/C and -1082A/G) and IL-6 -174G/C gene polymorphism and the risk of pneumonia-induced sepsis

Context: Association between inherited variants and the risks of sepsis is controversial.

Objective: To evaluate the risk of pneumonia-induced sepsis by examining its linkage with polymorphisms of IL-6 and IL-10.

Materials and methods: Samples were obtained from 188 pneumonia-induced sepsis patients, 162 pneumonia patients and 200 healthy controls.

Results: Subjects with IL-10 -1082 AA genotypes and IL-6 -174?CC genotype had a higher risk of sepsis and increased mRNA levels.

Conclusion: The variants of IL-10 -1082 A allele and IL-6 -174 C allele contributed to an increased risk of pneumonia-induced sepsis.     

Soluble CD40 ligand in haemodialysis patients: survival impact and cardiovascular prognostic role

Context: Soluble CD40 ligand (sCD40l) can predict cardiovascular events (CVE) and mortality in haemodialysis (HD) patients (short-, medium-term follow-up studies).

Objective: To evaluate the relationship between sCD40l and survival, CVE and mortality in HD patients on long-term follow-up.

Methods: We registered 46?HD patients’ baseline characteristics, mortality and CVE for 108 months.

Results: SCD40l correlated positively with C-reactive protein, was higher in survivors, but had no impact on survival and was not predictive for CVE or CV mortality.

Conclusion: The levels of sCD40l have no influence on survival or CVE and mortality in HD patients in a long-term follow-up.     

Predictors of leptin concentration and association with cardiovascular risk in patients with coronary artery disease: results from the AtheroGene study

Context: Leptin is produced in white adipose tissue, but also in human coronary atherosclerotic lesions.

Objective: The aim of this study is to assess the prognostic value of leptin in patients with proven coronary artery disease (CAD) (N?=?1907).

Methods: AtheroGene is a contemporary CAD cohort study (N?=?3229). Median follow-up time was 3.8 (Quartile 1/3 with 2.8/4.9) years.

Results: Leptin concentration was associated with a hazard ratio (HR) for the fully adjusted model of HR?=?1.32 in women but was not significant in men. The endpoint cardiovascular death and non-fatal myocardial infarction was observed in 167 patients.

Conclusion: In women with known CAD, increased leptin concentration is useful for predicting cardiovascular death and non-fatal myocardial infarction.