Nutrition of preterm infants in relation to bronchopulmonary dysplasia

Background

The pathogenesis of bronchopulmonary dysplasia (BPD) is multifactorial. In addition to prenatal inflammation, postnatal malnutrition also affects lung development.

Methods

A retrospective study was performed to analyse during the first two weeks of life the total, enteral and parenteral nutrition of premature infants (<31 weeks, birth weight ≤1500 g) born between 08/04 and 12/06.

Results

Ninety-five premature infants were analysed: 26 with BPD (27 ± 1 weeks) and 69 without BPD (28 ± 1 weeks). There was no statistical significant difference in the total intake of fluids, calories, glucose or protein and weight gain per day in both groups. The risk of developing BPD was slightly increased in infants with cumulative caloric intake below the minimal requirement of 1230 kcal/kg and a cumulative protein intake below 43.5 g/kg. Furthermore, the risk of developing BPD was significantly higher when infants had a cumulative fluid intake above the recommended 1840 ml/kg. In infants who developed BPD, the enteral nutrition was significantly lower than in non-BPD infants [456 ml/kg (IQR 744, 235) vs. 685 (IQR 987, 511)]. Infants who did not develop BPD reached 50% of total enteral feeding significantly faster [9.6 days vs. 11.5].

Conclusions

Preterm infants developing BPD received less enteral feeding, even though it was well compensated by the parenteral nutrient supply. Data suggest that a critical minimal amount of enteral feeding is required to prevent development of BPD; however, a large prospective clinical study is needed to prove this assumption.

     

Delay in diagnosis of pulmonary tuberculosis in low-and middle-income settings: systematic review and meta-analysis

Background

Assessment of delays in seeking care and diagnosis of tuberculosis is essential to evaluate effectiveness of tuberculosis control programs, and identify programmatic impediments. Thus, this review of studies aimed to examine the extent of patient, health system, and total delays in diagnosis of pulmonary tuberculosis in low- and middle- income countries.

Methods

It was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Electronic databases were searched to retrieve studies published from 2007 to 2015 including Pubmed central, Springer link, Hinari and Google scholar. Searching terms were pulmonary tuberculosis, health care seeking, health care seeking behavior, patient delay, diagnostic delay, health system delay, provider delay, and doctor delay. Retrieved studies were systematically reviewed and summarized using Comprehensive Meta-analysis software.

Results

Forty studies involving 18,975 patients qualified for systematic review, and 14 of them qualified for meta-analysis. The median diagnostic delay ranged from 30 to 366.5 days [IQR?=?44–77.8], with a 4–199 days [IQR?=?15–50] and 2–128.5 days [IQR?=?12–34] due to patient and health system delays, respectively. The meta-analysis showed 42% of pulmonary tuberculosis patients delayed seeking care by a month or more; uneducated patients [pooled OR?=?1.5, 95%CI?=?1.1–1.9] and those who sought initial care from informal providers [pooled OR?=?3, 95%CI?=?2.3–3.9] had higher odds of patient delay.

Conclusion

Delay in diagnosis is still a major challenge of tuberculosis control and prevention programs in low- and middle- income settings. Efforts to develop new strategies for better case-finding using the existing systems and improving patients’ care seeking behavior need to be intensified.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Sleep disturbances and semen quality in an Italian cross sectional study

Introduction

In order to obtain information about the relationship between sleep disturbances and sperm parameters, we analyzed data from a study conducted in a Italian Fertility Clinic, in men of couples seeking help for infertility.

Patients and methods

Male partners with or without a medical history of reproductive organ diseases (cryptorchidism, varicocele, orchitis, testicular torsion) were eligible for the study. There were 382 men evaluated from May 2014 to November 2016, all of whom completed a self-administered questionnaire on general lifestyle habits. Then all men underwent semen analysis. A total of 382 men aged 26 to 67 years (median age 39 year interquartile range 37–42) were recruited.

Main results

A total of 46.3% reported having sleep disturbances. In multivariate analysis, in absence of reproductive organ diseases, semen volume was lower in patients with difficulty in initiating sleep (2.0 ml, IQR 1.5–3.0 vs 3.0 ml, IQR 2.0–3.3, p = .01), whereas in presence of reproductive organ diseases motility A was lower in patients with early morning awakening (25.0%, IQR 15.0–35.0 vs. 40.0%, IQR 30.0–50.0, p = .001). In overweight men, semen volume was lower in patients with difficulty in initiating sleep (2.0 ml, IQR 1.5–3.0 vs 3.0 ml, IQR 2.0–3.0, p = .03). Moreover, among current smokers, patients with difficulty in initiating sleep had semen volume lower (1.5 ml, IQR 1.5–2.5 vs 3.0 ml, IQR 2.0–3.5, p = .0003) and sperm concentration higher (40 millions/ml, IQR 15–60 vs 10 millions/ml, IQR 5–50 p = .03) but total sperm count was not significant different.

Conclusion

Further studies are necessary to elucidate the relationship between sleep quality and semen parameters, which may have important public health implication.

     

Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study

Background

Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality.

Methods

We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing.

Results

We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3?days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2–4) and 6?days (stool; IQR 4.25–6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r?=???0.46, p?=?0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p?=?0.045).

Conclusions

The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients.

Trial registration

ClinicalTrials.gov ID NCT01782755. Registered February 4 2013.

     

No psychological distress in sportsmen aged 45 years and older after cardiovascular screening,including cardiac CT: The Measuring Athlete’s Risk of Cardiovascular events (MARC) study

Background

Psychological distress caused by cardiovascular pre-participation screening (PPS) may be a reason not to implement a PPS program. We assessed the psychological impact of PPS, including cardiac computed tomography (CT), in 318 asymptomatic sportsmen aged ≥45 years.

Methods

Coronary artery disease (CAD) was defined as a coronary artery calcium score ≥100 Agatson units and/or ≥50% luminal stenosis on contrast-enhanced cardiac CT. Psychological impact was measured with the Impact of Event Scale (IES) (seven items) on a six-point scale (grade 0–5). A sum score ≥19 indicates clinically relevant psychological distress. A Likert scale was used to assess overall experiences and impact on sports and lifestyle.

Results

A total of 275 participants (86.5% response rate, 95% CI 83–90%) with a mean age of 54.5 ± 6.4 years completed the questionnaires, 48 (17.5%, 95% CI 13–22%) of whom had CAD. The median IES score was 1 (IQR 0–2, [0–23]). IES was slightly higher in those with CAD (mean rank 175 vs. 130, p < 0.001). One participant (with CAD) experienced clinically relevant psychological distress (IES = 23). Participants reported numerous benefits, including feeling safer exercising (58.6%, 95% CI 53–65%) and positive lifestyle changes, especially in those with CAD (17.2 vs. 52.1%, p < 0.001). The majority were satisfied with their participation (93.8%, 95% CI 91–97%).

Conclusion

Cardiovascular PPS, including cardiac CT, causes no relevant psychological distress in older sportsmen. Psychological distress should not be a reason to forego screening in sportsmen.

     

A protocol for CABS-dock protein–peptide docking driven by side-chain contact information

Background

The characterization of protein–peptide interactions is a challenge for computational molecular docking. Protein–peptide docking tools face at least two major difficulties: (1) efficient sampling of large-scale conformational changes induced by binding and (2) selection of the best models from a large set of predicted structures. In this paper, we merge an efficient sampling technique with external information about side-chain contacts to sample and select the best possible models.

Methods

In this paper we test a new protocol that uses information about side-chain contacts in CABS-dock protein–peptide docking. As shown in our recent studies, CABS-dock enables efficient modeling of large-scale conformational changes without knowledge about the binding site. However, the resulting set of binding sites and poses is in many cases highly diverse and difficult to score.

Results

As we demonstrate here, information about a single side-chain contact can significantly improve the prediction accuracy. Importantly, the imposed constraints for side-chain contacts are quite soft. Therefore, the developed protocol does not require precise contact information and ensures large-scale peptide flexibility in the broad contact area.

Conclusions

The demonstrated protocol provides the extension of the CABS-dock method that can be practically used in the structure prediction of protein–peptide complexes guided by the knowledge of the binding interface.

     

Determination of fatty acid and sphingoid base composition of eleven ceramide subclasses in <Emphasis Type="Italic">stratum corneum</Emphasis> by UHPLC/scheduled-MRM

Introduction

Ceramides play a key role in skin barrier function in homeostatic and pathological conditions and can be sampled non-invasively through stratum corneum collection.

Objectives

To develop a novel UHPLC/Scheduled MRM method for the identification and relative distribution of eleven classes of ceramides, which are separated by UHPLC and determined by their specific retention times. The precise composition of the fatty acid and sphingoid base parts of each individual ceramide is determined via mass fragmentation.

Methods

More than 1000 human and pig ceramides were identified. Three human and minipig ceramide classes, CER[AS], CER[NS] and CER[EOS] have been investigated in depth.

Results

Sphingoid bases were characterized by a prevalence of chain lengths with sizes from C16 to C22, whereas fatty acids were mainly observed in the range of C22–C26. Overall, the ceramide profiles between human and minipig stratum corneum were similar. Differences in the CER[AS] and CER[NS] classes included a more homogeneous distribution of fatty acids (16–30 carbon atoms) in minipig, whereas in human longer fatty acid chains (>?24 carbon atoms) predominated.

Conclusion

The method will be useful for the analysis of healthy and pathological skin in various specie, and the measurement of the relative distribution of ceramides as biomarkers for pharmacodynamic studies.

     

Association between viscoelastic tests-guided therapy with synthetic factor concentrates and allogenic blood transfusion in liver transplantation: a before-after study

Background

Perioperative bleeding and transfusion are important causes of morbidity and mortality in patients undergoing liver transplantation. The aim of this study is to assess whether viscoelastic tests-guided therapy with the use of synthetic factor concentrates impact transfusion rates of hemocomponents in adult patients undergoing liver transplantation.

Methods

This is an interventional before-after comparative study. Patients undergoing liver transplantation before the implementation of a protocol using thromboelastometry and synthetic factor concentrates were compared to patients after the implementation. Primary outcome was transfusion of any hemocomponents. Secondary outcomes included: transfusion of red blood cells (RBC), fresh frozen plasma (FFP), cryoprecipitate or platelets, clinical complications, length of stay and in-hospital mortality.

Results

A total of 183 patients were included in the control and 54 in the intervention phase. After propensity score matching, the proportion of patients receiving any transfusion of hemocomponents was lower in the intervention phase (37.0 vs 58.4%; OR, 0.42; 95% CI, 0.20–0.87; p?=?0.019). Patients in the intervention phase received less RBC (30.2 vs 52.5%; OR, 0.21; 95% CI, 0.08–0.56; p?=?0.002) and FFP (5.7 vs 27.3%; OR, 0.11; 95% CI, 0.03–0.43; p?=?0.002). There was no difference regarding transfusion of cryoprecipitate and platelets, complications related to the procedure, hospital length of stay and mortality.

Conclusions

Use of a viscoelastic test-guided transfusion algorithm with the use of synthetic factor concentrates reduces the transfusion rates of allogenic blood in patients submitted to liver transplantation.

Trial registration

This trial was registered retrospectively on November 15th, 2018 – clinicaltrials.gov – Identifier: NCT03756948.

     

Chilling slows anaerobic metabolism to improve anoxia tolerance of insects

Background

Insects are renowned for their ability to survive anoxia. Anoxia tolerance may be enhanced during chilling through metabolic suppression.

Aims

Here, the metabolomic response of insects to anoxia, both with and without chilling, for different durations (12–36 h) was examined to assess the potential cross-tolerance mechanisms.

Results

Chilling during anoxia (cold anoxia) significantly improved survival relative to anoxia at warmer temperatures. Reduced intermediate metabolites and increased lactic acid, indicating a switch to anaerobic metabolism, were characteristic of larvae in anoxia.

Conclusions

Anoxia tolerance was correlated survival improvements after cold anoxia were correlated with a reduction in anaerobic metabolism.

     

The negative effect of ANGPTL8 on HDL-mediated cholesterol efflux capacity

Background

It is well known that angiopoietin-like protein 8 (ANGPTL8) exerts its effects on lipid metabolism through the inhibition of lipoprotein lipase and subsequent elevation of plasma triglyceride. However, it is not clear whether ANGPTL8 could affect lipid metabolism via other pathways. The study was aimed to investigate the effects of ANGPTL8 on the function of high-density lipoprotein (HDL), which plays a protective role in atherosclerosis progression.

Methods

Two hundred and ten subjects were recruited. Plasma ANGPTL8 was measured by enzyme-linked immunosorbent assays. Cholesterol efflux capacity was chosen as the biomarker of HDL function and measured via H³-cholesterol loading THP-1 cell models.

Results

ANGPTL8 exhibited no significant difference between CAD group and nonCAD group, but ANGPTL8 in DM group was significantly higher than that in the nonDM group [568.3 (406.2–836.8) vs 458.2 (356.8–755.6), P?=?0.023]. Compared to controls, subjects in CAD group and DM group exhibited significantly lower cholesterol efflux capacity [CAD: 14.58?±?2.06 vs 12.51?±?2.83%, P?<?0.0001; DM: 13.62?±?2.57 vs 12.34?±?3.16%, P?=?0.0099]. ANGPTL8 was inversely correlated with cholesterol efflux capacity (r?=???0.188, P?<?0.01). Regression analysis revealed that plasma ANGPTL8 was an independent contributor to cholesterol efflux capacity (standardized β?=???0.143, P?=?0.023).

Conclusion

ANGPTL8 presents a negative effect on HDL-mediated cholesterol efflux capacity.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.

     

Cardiac rehabilitation in patients who underwent primary percutaneous coronary intervention for acute myocardial infarction: determinants of programme participation and completion

Background

Hospital length of stay after acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (pPCI) has reduced, resulting in more limited patient education during admission. Therefore, systematic participation in cardiac rehabilitation (CR) has become more essential. We aimed to identify patient-related factors that are associated with participation in and completion of a CR programme.

Methods

We identified 3,871 consecutive AMI patients who underwent pPCI between 2003 and 2011. These patients were linked to the database of Capri CR, which provides dedicated, multi-disciplinary CR. ‘Participation’ was defined as registration at Capri CR within 6 months after pPCI. CR was ‘complete’ if a patient undertook the final exercise test.

Results

In total, 1,497 patients (39%) were registered at Capri CR. Factors independently associated with CR participation included age (<50 vs. >70 year: odds ratio (OR) 7.0, 95% confidence interval (CI) 5.1–9.6), gender (men vs. women: OR 1.9, 95% CI 1.3–1.8), index diagnosis (ST-elevation myocardial infarction [STEMI] vs. non-ST-elevation myocardial infarction [NSTEMI]: OR 2.4, 95% CI 2.0–2.7) and socio-economic status (high vs. low: OR 2.0, 95% CI 1.6–2.5). The model based on these factors discriminated well (c-index 0.75). CR programme completion was 80% and was inversely related with diabetes, current smoking and previous MI. The discrimination of the model based on these factors was poor (c-index 0.59).

Conclusions

Only a minority of AMI/pPCI patients participated in a CR programme. Completion rates, however, were better. Increased physician and patient awareness of the benefits of CR are still needed, with focus on the elderly, women and patients with low socio-economic status.

     

Metabolomics approach for predicting response to neoadjuvant chemotherapy for colorectal cancer

Introduction

Colorectal cancer (CRC) is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. Only some CRC patients will benefit from neoadjuvant chemotherapy (NACT).

Objectives

An accurate prediction of response to NACT in CRC patients would greatly facilitate optimal personalized management, which could improve their long-term survival and clinical outcomes.

Methods

In this study, plasma metabolite profiling was performed to identify potential biomarker candidates that can predict response to NACT for CRC. Metabolic profiles of plasma from non-response (n?=?30) and response (n?=?27) patients to NACT were studied using UHPLC–quadruple time-of-flight)/mass spectrometry analyses and statistical analysis methods.

Results

The concentrations of nine metabolites were significantly different when comparing response to NACT. The area under the receiver operating characteristic curve value of the potential biomarkers was up to 0.83 discriminating the non-response and response group to NACT, superior to the clinical parameters (carcinoembryonic antigen and carbohydrate antigen 199).

Conclusion

These results show promise for larger studies that could result in more personalized treatment protocols for CRC patients.

     

Accumulation of Fascin<Superscript>+</Superscript> cells during experimental autoimmune neuritis

Background

Experimental autoimmune neuritis (EAN) is a well-known animal model of human demyelinating polyneuropathies and is characterized by inflammation and demyelination in the peripheral nervous system. Fascin is an evolutionarily highly conserved cytoskeletal protein of 55 kDa containing two actin binding domains that cross-link filamentous actin to hexagonal bundles.

Methods

Here we have studied by immunohistochemistry the spatiotemporal accumulation of Fascin?+?cells in sciatic nerves of EAN rats.

Results

A robust accumulation of Fascin?+?cell was observed in the peripheral nervous system of EAN which was correlated with the severity of neurological signs in EAN.

Conclusion

Our results suggest a pathological role of Fascin in EAN.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticphatology.diagnomx.eu/vs/6734593451114811

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

Isolation of human mesenchymal stem cells from amnion,chorion, placental decidua and umbilical cord: comparison of four enzymatic protocols

Objective

To compare four enzymatic protocols for mesenchymal stem cells (MSCs) isolation from amniotic (A-MSC) and chorionic (C-MSC) membranes, umbilical cord (UC-MSC) and placental decidua (D-MSC) in order to define a robust, practical and low-cost protocol for each tissue.

Results

A-MSCs and UC-MSCs could be isolated from all samples using trypsin/collagenase-based protocols; C-MSCs could be isolated from all samples with collagenase- and trypsin/collagenase-based protocols; D-MSCs were isolated from all samples exclusively with a collagenase-based protocol.

Conclusions

The trypsin-only protocol was least efficient; the collagenase-only protocol was best for C-MSCs and D-MSCs; the combination of trypsin and collagenase was best for UC-MSCs and none of tested protocols was adequate for A-MSCs isolation.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.