Presence of arachidonoyl-carnitine is associated with adverse cardiometabolic responses in hypertensive patients treated with atenolol

Introduction

Atenolol, a commonly prescribed β blocker for hypertension, is also associated with adverse cardiometabolic effects such as hyperglycemia and dyslipidemia. Knowledge of the mechanistic underpinnings of these adverse effects of atenolol is incomplete.

Objective

We sought to identify biomarkers associated with risk for these untoward effects of atenolol. We measured baseline blood serum levels of acylcarnitines (ACs) that are involved in a host of different metabolic pathways, to establish associations with adverse cardiometabolic responses after atenolol treatment.

Methods

Serum samples from Caucasian hypertensive patients (n = 224) who were treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study were interrogated using a quantitative LC/MS assay for a large number of unique ACs in serum. For the 23 ACs that were detected in serum from ≥80 % of all patients, we conducted linear regression for changes in cardiometabolic factors with baseline AC levels, baseline cardiometabolic factors, age, sex, and BMI as covariates. For the 5 ACs that were detected in serum from 20 to 79 % of the patients, we similarly modeled changes in cardiometabolic factors, but with specifying the AC as present/absent in the regression.

Results

Among the 28 ACs, the presence (vs. absence) of arachidonoyl-carnitine (C20:4) was significantly associated with increased glucose (p = 0.0002), and was nominally associated with decreased plasma HDL-C (p = 0.017) and with less blood pressure (BP) lowering (p = 0.006 for systolic BP, p = 0.002 for diastolic BP), after adjustment.

Conclusion

Serum level of C20:4 is a promising biomarker to predict adverse cardiometabolic responses including glucose and poor antihypertensive response to atenolol.

     

NMR analysis of the CSF and plasma metabolome of rigorously matched amyotrophic lateral sclerosis,Parkinson’s disease and control subjects

Introduction

Amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are two severe neurodegenerative disorders for which the disease mechanisms are poorly understood and reliable biomarkers are absent.

Objectives

To identify metabolite biomarkers for ALS and PD, and to gain insights into which metabolic pathways are involved in disease.

Methods

Nuclear magnetic resonance (NMR) metabolomics was utilized to characterize the metabolite profiles of cerebrospinal fluid (CSF) and plasma from individuals in three age, gender, and sampling-date matched groups, comprising 22 ALS, 22 PD and 28 control subjects.

Results

Multivariate analysis of NMR data generated robust discriminatory models for separation of ALS from control subjects. ALS patients showed increased concentrations of several metabolites in both CSF and plasma, these are alanine (CSF fold change = 1.22, p = 0.005), creatine (CSF-fc = 1.17, p = 0.001), glucose (CSF-fc = 1.11, p = 0.036), isoleucine (CSF-fc = 1.24, p = 0.002), and valine (CSF-fc = 1.17, p = 0.014). Additional metabolites in CSF (creatinine, dimethylamine and lactic acid) and plasma (acetic acid, glutamic acid, histidine, leucine, pyruvate and tyrosine) were also important for this discrimination. Similarly, panels of CSF-metabolites that discriminate PD from ALS and control subjects were identified.

Conclusions

The results for the ALS patients suggest an affected creatine/creatinine pathway and an altered branched chain amino acid (BCAA) metabolism, and suggest links to glucose and energy metabolism. Putative metabolic markers specific for ALS (e.g. creatinine and lactic acid) and PD (e.g. 3-hydroxyisovaleric acid and mannose) were identified, while several (e.g. creatine and BCAAs) were shared between ALS and PD, suggesting some overlap in metabolic alterations in these disorders.

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

     

Cinnamon: does it hold its promises in cows? Using non-targeted blood serum metabolomics profiling to test the effects of feeding cinnamon to dairy cows undergoing lactation-induced insulin resistance

Introduction

Cinnamon exerts insulin-enhancing activity in vitro and was demonstrated to improve blood glucose and lipid profiles in several human studies. Such effects may have an impact on metabolically stressed cows.

Objective

To study the effects of cinnamon supplementation during the transition from late pregnancy to early lactation on the metabolism in dairy cows.

Methods

Twenty-four Holstein cows (n?=?8/group) were assigned to either the control group (CTR; without supplementation) or the supplementation groups [supplemental cinnamon at 20 (LCIN) or 40 (HCIN) g/cow per day (d)] from 28 d before calving until 21 d thereafter. Blood samples were assayed for glucose, nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and insulin; an index estimating insulin sensitivity (RQUICKI) was calculated. The serum metabolome was characterized in the samples collected from d 14 using a non-targeted approach.

Results

The serum concentrations of glucose and insulin did not differ among groups and followed a similar pattern over time. The serum NEFA concentrations were greater in LCIN (d 2, 7, and 14) and HCIN (d 14) than in CTR. On d 14 and 21, LCIN and HCIN had greater serum BHBA concentrations than CTR cows. The top 10 metabolites identified with significantly higher levels in the supplemented than the CTR cows were related to fatty acid metabolism.

Conclusion

The data suggest lipolytic and ketogenic effects of cinnamon supplementation in dairy cows during the transition from late gestation to early lactation. The fatty acid metabolites found elevated in the supplemented cows point towards impaired mitochondrial fatty acid β-oxidation.

     

Medical students and physical education students as CPR instructors: an appropriate solution to the CPR-instructor shortage in secondary schools?

Background

Integrating cardiopulmonary resuscitation (CPR) training in secondary schools will increase the number of potential CPR providers. However, currently too few certified instructors are available for this purpose. Training medical students and physical education student teachers to become CPR instructors could decrease this shortage.

Aim

Examine whether medical students and physical education student teachers can provide CPR training for secondary school pupils as well as (i.?e., non-inferior to) registered nurses.

Methods

A total of 144 secondary school pupils were randomly assigned to CPR training by a registered nurse (n = 12), a  medical student (n = 17) or a physical education student teacher (n = 15). CPR performance was assessed after training and after eight weeks in a simulated cardiac arrest scenario on a resuscitation manikin, using manikin software and video recordings.

Results

No significant differences were found between the groups on the overall Cardiff Test scores and the correctness of the CPR techniques during the post-training and retention test. All pupils showed sufficient CPR competence, even after eight weeks.

Conclusion

Training by medical students or physical education student teachers is non-inferior to training by a registered nurse, suggesting that school teachers, student teachers and medical students can be recruited for CPR training in secondary schools.

     

Postprandial metabolite profiles associated with type 2 diabetes clearly stratify individuals with impaired fasting glucose

Introduction

Fasting metabolite profiles have been shown to distinguish type 2 diabetes (T2D) patients from normal glucose tolerance (NGT) individuals.

Objectives

We investigated whether, besides fasting metabolite profiles, postprandial metabolite profiles associated with T2D can stratify individuals with impaired fasting glucose (IFG) by their similarities to T2D.

Methods

Three groups of individuals (age 45–65 years) without any history of IFG or T2D were selected from the Netherlands Epidemiology of Obesity study and stratified by baseline fasting glucose concentrations (NGT (n?=?176), IFG (n?=?186), T2D (n?=?171)). 163 metabolites were measured under fasting and postprandial states (150 min after a meal challenge). Metabolite profiles specific for a high risk of T2D were identified by LASSO regression for fasting and postprandial states. The selected profiles were utilised to stratify IFG group into high (T2D probability?≥?0.7) and low (T2D probability?≤?0.5) risk subgroups. The stratification performances were compared with clinically relevant metabolic traits.

Results

Two metabolite profiles specific for T2D (n_fasting = 12 metabolites, n_postprandial = 4 metabolites) were identified, with all four postprandial metabolites also being identified in the fasting state. Stratified by the postprandial profile, the high-risk subgroup of IFG individuals (n?=?72) showed similar glucose concentrations to the low-risk subgroup (n?=?57), yet a higher BMI (difference: 3.3 kg/m² (95% CI 1.7–5.0)) and postprandial insulin concentrations (21.5 mU/L (95% CI 1.8–41.2)).

Conclusion

Postprandial metabolites identified T2D patients as good as fasting metabolites and exhibited enhanced signals for IFG stratification, which offers a proof of concept that metabolomics research should not focus on the fasting state alone.

     

Effect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: the JAMP study

Background

To investigate the ameliorating effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood glucose control in patients with type 2 diabetes mellitus who were previously untreated with or who have a poor responsive to existing antidiabetic drugs.

Methods

Sitagliptin (50 mg/day) was added on to the pre-existing therapy for type 2 diabetes and changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline and performed exploratory analysis.

Results

HbA1c levels were significantly decreased after 1 month of treatment compared to baseline, with a mean change in HbA1c level from baseline of ?0.73% (range, ?0.80 to ?0.67) in the entire study population at 3 months. Patients who received a medium dose of glimepiride showed the least improvement in HbA1c levels. The percentage of patients who achieved an HbA1c level of <7.0% significantly increased after 1 month of treatment, reaching 53.1% at 3 months. The percentage of patients who achieved a fasting blood glucose level of <130 mg/dL significantly increased after 1 month of treatment, reaching 50.9% at 3 months.

Conclusions

Sitagliptin improved the HbA1c level and rate of achieving the target control levels in patients with type 2 diabetes mellitus who were previously untreated with, or poorly responsive to, existing antidiabetic drugs. Thus, sitagliptin is expected to be useful in this patient group. However, the additional administration of sitagliptin in patients treated with medium-dose glimepiride only slightly improved blood glucose control when corrected for baseline HbA1c level.

     

Regular enzyme recovery enhances cellulase production by <Emphasis Type="Italic">Trichoderma reesei</Emphasis> in fed-batch culture

Objective

To protect the enzymes during fed-batch cellulase production by means of partial enzyme recovery at regular intervals.

Results

Extracellular enzymes were partially recovered at the intervals of 1, 2, or 3 days. Mycelia were also removed to avoid contamination. Increases in the total harvested cellulase (24–62%) and β-glucosidase (22–76%) were achieved. In fermentor cultivation when the enzymes were recovered every day with 15% culture broth. The total harvested cellulase and β-glucosidase activity increased by 43 and 58%, respectively, with fungal cell concentration maintained at 3.5–4.5 g l^?1.

Conclusion

Enzyme recovery at regular intervals during fed-batch cellulase cultivation could protect the enzyme in the culture broth and enhance the enzyme production when the fungal cell concentration is maintained in a reasonable range.

     

Application of residual polysaccharide-degrading enzymes in dried shiitake mushrooms as an enzyme preparation in food processing

Objective

To examine the activities of residual enzymes in dried shiitake mushrooms, which are a traditional foodstuff in Japanese cuisine, for possible applications in food processing.

Results

Polysaccharide-degrading enzymes remained intact in dried shiitake mushrooms and the activities of amylase, β-glucosidase and pectinase were high. A potato digestion was tested using dried shiitake powder. The enzymes reacted with potato tuber specimens to solubilize sugars even under a heterogeneous solid-state condition and that their reaction modes were different at 38 and 50 °C.

Conclusion

Dried shiitake mushrooms have a potential use in food processing as an enzyme preparation.

     

Erythropoietin stimulates the coronary collateral development in patients with coronary chronic total occlusion

Objective

Erythropoietin (EPO) improves cardiac function and induces neovascularisation in post-myocardial infarction heart failure. The aim of this study was to analyse the association between the serum erythropoietin level and coronary collateral development in patients with coronary artery disease and chronic total occlusion.

Methods

A total of 168 patients consisting of 117 with coronary artery disease (CAD, (62 with chronic total occlusion (CTO), 55 without CTO)) and 51 with healthy coronary arteries were included in the study. The patients were assigned as coronary artery disease without CTO (group 0), CAD with CTO (group 1: poor collateral development, group 2: good collateral development) and normal coronary arteries (group 3).

Results

There was a significant positive correlation between serum EPO levels and the Rentrop scores in angiography (r = 0.243, p = 0.001). Similarly, a positive correlation was found between serum EPO levels and the Syntax scores (r = 0.253, p = 0.001). Echocardiography revealed a negative correlation between serum EPO levels and the cardiac ejection fraction (r = ?0.210, p = 0.006).

Conclusions

Serum EPO is a useful biomarker for coronary collateral development in patients with CTO.

     

Nuclear magnetic resonance-based metabolomics of OCT-embedded frozen kidney samples in mouse and man following standardized pre-analytics

Introduction

Pre-analytical processing significantly affects tissue metabolomes. Since most frozen kidney samples are stored after embedding, standardization of cryoprotective medium removal before metabolomics is essential.

Objectives

We used rodent and human kidney samples to develop an easy and robust pre-analytical procedure compatible with ¹H-nuclear magnetic resonance (NMR)-based metabolomics.

Methods

In mice, renal ischemia was induced for 30 min, followed by 48-h reperfusion (I/R, n?=?6). Right kidneys were transversally cut in two fragments, and snap-frozen in liquid nitrogen (LN2) or in Optimal Cutting Temperature ^® (OCT) fixative. In man, double kidney biopsies were simultaneously obtained before transplantation (n?=?15), and snap-frozen in LN2 or OCT.

Results

¹H-NMR spectrum of pure OCT highlighted two major peaks, i.e. from 3.4 to 4.2 ppm (47.2%) and from 1.2 to 2.2 ppm (42.5%). ¹H-NMR spectra of mouse OCT kidneys were biased at 3.7. By contrast, ¹H-NMR analyses of mouse OCT kidneys iteratively rinsed in saline significantly discriminated sham versus I/R groups, with Q² at 0.695 (to be compared with Q² at 0.866 for LN2 sham vs. I/R kidneys). Discriminant metabolites were analogous in both OCT and LN2 kidneys, with a correlation coefficient of 0.83. In man, iteratively rinsing OCT kidneys in saline eliminated the spectral 3.7-peak, thereby making metabolomes of OCT kidneys interpretable and similar to LN2 samples, with a correlation coefficient of 0.73.

Conclusion

NMR metabolomics using OCT-frozen kidney samples is valuable in mouse and man, following standardized OCT removal. This may help use residual biobanked human tissues to better understand renal pathophysiology.

     

Perceived stress and bruxism in university students

Background

Many studies have shown the correlation between bruxism and stress that affects the quality of life of university students. The present study highlights this correlation—for the first time—in a group of university students in Italy.

Methods

We have investigated the prevalence of awake and asleep bruxism and its correlation with perceived stress in a group of 278 Italian undergraduate students (117 M). A self report questionnaire was constructed using a socio-demographic test, the Perceived Stress Scale (PSS) and the item n. 8 of the Fonseca Questionnaire for presence of bruxism.

Results

The perceived stress score using PSS-10 scale was 32.2 (SD 4.6, 95% CL 31.6–32.7) for all the subjects, with significant gender difference: M = 31.2 and F = 32.9 (P = 0.0019). The prevalence for awake bruxism was 37.9% (F = 40.8%; M = 34.2%,), while for sleep bruxism was 31.8% (F = 33.3%; M = 29.1%), both without significant gender difference. A positive correlation, with significant concordance and dependence, between stress score and awake bruxism was present for male students only.

Conclusions

University students showed higher bruxism and stress levels compared to the general population, with higher stress for females, but, even if female students show higher stress, a correlation between stress and bruxism exists only for male gender. Further studies should be performed.

     

Altered plasma acylcarnitine and amino acid profiles in type 2 diabetic kidney disease

Introduction

Dysregulation of acylcarnitines (AcylCNs) and amino acids metabolism have implicated in abnormality of fatty acid oxidation in type 2 diabetes (T2D). However, it is not well known whether altered plasma AcylCN, and amino acid profiles are associated with albuminuria or diabetic nephropathy (DN) in T2D.

Objective

The aim of this study was to elucidate alterations in plasma levels of AcylCNs and amino acids with respect to the T2D patients with various stages of albuminuria.

Methods

We recruited 52 healthy subjects as control, and 156 T2D patients which were divided into 52 normoalbuminuria, 52 microalbuminuria, and 52 macroalbuminuria. Plasma 37 AcylCNs and 12 amino acids were analyzed by tandem mass spectrometry.

Results

We found that T2D with normoalbuminuria and microalbuminuria had lower shot-, medium-, and long-chain AcylCNs, whereas T2D with macroalbuminuria had higher short-and medium-chain AcylCNs and lower long-chain AcylCNs than healthy subjects. Moreover, estimated glomerular filtration rate (eGFR) was a negative, independent and significant predictor of albumin to creatinine ratio (ACR) levels (β = ?0.376, P < 0.001), whereas plasma Low-density lipoprotein cholesterol (LDL-C) was significantly and positively associated with ACR levels (β = 0.169, P = 0.049). Furthermore, multivariate ordinal logistic regression analysis revealed that isobutyrylcarnitine (C4) was a positive, independent, and significant predictor of ACR levels with higher odds of having T2D patients with progression normoalbuminuria to microalbuminuria [OR = 9.93, 95 % CI (3.51–28.05), P < 0.001].

Conclusions

The findings suggest that plasma C4 may serve as a potential biomarker for the early stages of DN.

     

Metabolomics of biomarker discovery in ovarian cancer: a systematic review of the current literature

Introduction

Metabolomics is the emerging member of “omics” sciences advancing the understanding, diagnosis and treatment of many cancers, including ovarian cancer (OC).

Objectives

To systematically identify the metabolomic abnormalities in OC detection, and the dominant metabolic pathways associated with the observed alterations.

Methods

An electronic literature search was performed, up to and including January 15th 2016, for studies evaluating the metabolomic profile of patients with OC compared to controls. QUADOMICS tool was used to assess the quality of the twenty-three studies included in this systematic review.

Results

Biological samples utilized for metabolomic analysis include: serum/plasma (n = 13), urine (n = 4), cyst fluid (n = 3), tissue (n = 2) and ascitic fluid (n = 1). Metabolites related to cellular respiration, carbohydrate, lipid, protein and nucleotide metabolism were significantly altered in OC. Increased levels of tricarboxylic acid cycle intermediates and altered metabolites of the glycolytic pathway pointed to perturbations in cellular respiration. Alterations in lipid metabolism included enhanced fatty acid oxidation, abnormal levels of glycerolipids, sphingolipids and free fatty acids with common elevations of palmitate, oleate, and myristate. Increased levels of glutamine, glycine, cysteine and threonine were commonly reported while enhanced degradations of tryptophan, histidine and phenylalanine were found. N-acetylaspartate, a brain amino acid, was found elevated in primary and metastatic OC tissue and ovarian cyst fluid. Further, elevated levels of ketone bodies including 3-hydroxybutyrate were commonly reported. Increased levels of nucleotide metabolites and tocopherols were consistent through out the studies.

Conclusion

Metabolomics presents significant new opportunities for diagnostic biomarker development, elucidating previously unknown mechanisms of OC pathogenesis.

     

How resilient is the general population to heatwaves? A knowledge survey from the ENHANCE project in Brussels and Amsterdam

Background

Studies have shown an increase in mortality and morbidity during heatwaves, especially among the elderly. We assessed the knowledge of the general population of Brussels and Amsterdam on groups at risk and protective measures for heat-related health effects.

Results

Six locations with mixed populations were selected in each city. Passer-by’s in both cities were asked to participate in a short survey. Respondents in Brussels (n = 120) had significantly more knowledge on risk groups and protective measures than respondents in Amsterdam (n = 133). In both cities, individuals with higher education had better knowledge on risk groups and protective measures than individuals with lower education.

Conclusions

Efforts at heat-awareness raising must be strengthened, especially in Amsterdam, and public health actions should effectively target vulnerable groups with lower education in both cities.

     

Weight loss and weight maintenance obtained with or without GLP-1 analogue treatment decrease branched chain amino acid levels

Introduction

Increased levels of circulating branched chain amino acids (BCAAs), as well as phenylalanine, and tyrosine have been suggested to be involved in the pathogenesis of insulin resistance and type 2 diabetes. However, it is unknown how these metabolites are affected by weight loss, and during weight-maintaining treatment with glucagon-like peptide-1 receptor agonist (GLP-1 RA).

Objective

We aimed to characterize changes in metabolites related to protein turnover and glycolysis after a weight loss intervention followed by long term weight maintenance with/without GLP-1 RA.

Methods

Fifty-eight obese individuals underwent a diet-induced 12 % body weight loss during 8 weeks. Participants were randomized to weight maintenance with or without administration of the GLP-1 RA liraglutide (1.2 mg/day) for 52 weeks. Metabolomic profiling by high-throughput proton nuclear magnetic resonance spectroscopy was used for quantification of metabolites.

Results

The weight loss was maintained in both groups and was associated with 9–20 % decreases in plasma concentrations of alanine, phenylalanine, histidine, tyrosine and the BCAAs leucine, isoleucine and valine (p < 0.05). Plasma citrate levels increased during weight loss (p = 5.2 × 10^?15) and showed inverse correlation with insulin resistance measured by HOMA–IR levels (r = ?0.318, p = 0.025). Valine concentrations were lower in the control group compared to the GLP-1RA group during weight maintenance (p = 0.005).

Conclusion

Weight loss is associated with marked changes in plasma concentrations of eight amino acids and glycolysis-related metabolites. Levels of the suggested type 2 diabetes risk markers (BCAAs) remain low during long-term weight maintenance.

     

High resolution metabolomic analysis of ASD human brain uncovers novel biomarkers of disease

Introduction

Autism spectrum disorders (ASD) is a group of neurodevelopmental disorders believed to have a multifactorial basis. Presently, diagnosis is based on behavioral and developmental signs in children before the age of 3 and no reliable clinical biomarkers are available for early detection.

Objectives

This study aimed to biochemically profile the cerebellum from post-mortem human brain from ASD sufferers (n = 11) and compare their profiles to that of age-matched controls (n = 11) with no known brain disorder.

Methods

Using liquid chromatography combined with LTQ-Orbitrap mass spectrometry we detected 14,328 features in ESI+ mode in polar extracts of post-mortem brain.

Results

Of these only 37 were found to be statistically significantly different between ASD and controls (p < 0.05; fdr < 0.05). A panel of four features had a predictive power of 96.64 %, following statistical cross validation, for ASD detection. This model produced an AUC = 0.874 (CI 0.768–0.944) and a Fisher’s exact score of p = 4.50E?29.

Conclusion

Whilst at this time we were unable to chemically identify the four features of interest we believe that this study underscores the potential value of high resolution metabolomics for the study of ASD. Further characterization of the polar metabolome of post mortem ASD brains could lead to the identification of potential biomarkers and novel therapeutics for the disease. The development of accurate biomarkers could assist in the early detection of ASD and promote early intervention strategies to improve outcome.

     

Introducing transcatheter aortic valve implantation with a new generation prosthesis: Institutional learning curve and effects on acute outcomes

Objectives

We present our single-centre experience with the direct flow medical (DFM) trans-catheter aortic valve implantation (TAVI) prosthesis addressing the impact of learning curve upon outcomes.

Background

The DFM has been recently introduced for TAVI. The prosthesis presents original design and implantation features.

Methods

Patients were divided into three groups according to the chronological implantation sequence that reflected technical skills acquisition of the entire team.

Results

Group I included the first 20 patients (early learning phase), group II the second 20 patients (proctoring to other members of the team), and group III the following 93 patients (technique consolidation). Differences in baseline and procedural variables were analysed. Nonparametric correlation and linear regression were used to identify changes according to institutional cumulative experience. There was a significant correlation between catheterisation time and institutional experience (rho = ?0.4; p < 0.0001) confirmed at linear regression (beta = ?0.2; p = 0.001; CI: ?0.3?–??0.08). Moreover, there was lower rate of valve retrieval in group III (15% vs. 20% vs. 10%; p = 0.5). No intra-procedural mortality was reported and improved early safety (at 30 days) was observed (80% vs. 85% vs. 87.1; p = 0.7). At hospital discharge, valve haemodynamic performance was satisfactory with only mild regurgitation in 10% (I), 20% (II), and 9.7% (III) (p = 0.8).

Conclusions

DFM adequate sizing and implantation can be achieved after the early learning phases. A significant reduction in catheterisation time is reported after the first 20 patients. Results remain satisfactory during the proctoring and technical consolidation phase.

     

Daily variation and effect of dietary folate on urinary pteridines

Introduction

Urinary pteridines are putative molecular biomarkers for noninvasive cancer screening and prognostication. Central to their translational biomarker development is the need to understand the sources and extent of their non-epidemiological variation.

Objectives

This study was designed to characterize the two primary sources of urinary pteridine variance: daily variation and the effect of dietary folate.

Methods

Daily variation was studied by collecting urine specimens (n = 81) three times daily for 3 days. The effect of dietary folate was investigated in a treatment study in which urine specimens (n = 168) were collected daily during a control week and a treatment week during which participants received dietary folate supplements. Measurements of six urinary pteridines were made using high-performance liquid chromatography–tandem mass spectrometry. Coefficients of variation were calculated to characterize daily variance between and within subjects, while nearest neighbor non-parametric analyses were used to identify diurnal patterns and measure dietary folate effects.

Results

Daily variance was approximately 35 % RSD for both within-day and between-day periods for most pteridines. Diurnal patterns in response to circadian rhythms were similarly observed for urinary pteridines. Folate supplementation was shown to alter urinary pteridine profiles in a pathway dependent manner, suggesting that dietary folate may regulate endogenous neopterin and biopterin biosynthesis.

Conclusions

Urinary pteridine levels were found to be responsive to both daily variation and folate supplementation. These findings provide new insights into pteridine biosynthesis and regulation as well as useful information for the design of future clinical translational research.

     

Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy

Introduction

Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles.

Objectives

We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB.

Methods

A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20–22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer.

Results

Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = ?0.62, p < 0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20–22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20–22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB < 37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64–1) in the SYM women, whilst other metabolites were not.

Conclusion

High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation.