scholarly journals Metabolomics pilot study identifies circadian desynchronization and distinct intra-patient variability patterns in critical illness

2019 ◽  
Author(s):  
Elizabeth R. Lusczek ◽  
Lee Parsons ◽  
Jesse Elder ◽  
Stephen B. Harvey ◽  
Mariya Skube ◽  
...  
Keyword(s):  
Pilot Study ◽  
Circadian Rhythms ◽  
Vital Signs ◽  
Principal Component ◽  
Underlying Disease ◽  
Plasma Metabolites ◽  
Metabolic Profiles ◽  
Healthy Controls ◽  
Icu Patients ◽  
Sound Levels

AbstractBackgroundSynchronized circadian rhythms play a key role in coordinating physiologic health. Desynchronized circadian rhythms may predispose individuals to disease or be indicative of underlying disease. Intensive care unit (ICU) patients likely experience desynchronized circadian rhythms due to disruptive environmental conditions in the ICU and underlying pathophysiology. This observational pilot study was undertaken to determine if circadian rhythms are altered in ICU patients relative to healthy controls by profiling circadian rhythms in vital signs and plasma metabolites.MethodsWe monitored circadian rhythms in 5 healthy controls and 5 ICU patients for 24 hours. Heart rate and blood pressure were measured every 30 minutes, temperature was measured every hour, and blood was sampled for mass spectrometry-based plasma metabolomics every 4 hours. Bedside sound levels were measured every minute. Circadian rhythms were evaluated in vitals and plasma metabolites individually and in each group using the cosinor method.ResultsICU patient rooms were significantly louder than healthy controls’ rooms and average noise levels were above EPA recommendations. Healthy controls generally had significant circadian rhythms individually and as a group. While a few ICU patients had significant circadian rhythms in isolated variables, no significant rhythms were identified in ICU patients as a group, except in cortisol. This indicates a lack of coherence in circadian phases and amplitudes among ICU patients. Finally, principal component analysis of metabolic profiles showed surprising patterns in plasma sample clustering. Each ICU patient’s samples were clearly discernable in individual clusters, separate from a single cluster of healthy controls.ConclusionsICU patients’ circadian rhythms show significant desynchronization compared to healthy controls. Clustering of plasma metabolic profiles suggests that metabolomics could be used to track individual patients’ clinical courses longitudinally. Our results show global disordering of metabolism and the circadian system in ICU patients which should be characterized further in order to determine implications for patient care.

scholarly journals Altered Blood Levels of Vitamin D, Cathelicidin and Parathyroid Hormone in Patients with Sepsis—a Pilot Study

2017 ◽  
Vol 45 (1) ◽  
pp. 36-45 ◽  
Author(s):  
T. Greulich ◽  
W. Regner ◽  
M. Branscheidt ◽  
C. Herr ◽  
A. R. Koczulla ◽  
...  
Keyword(s):  
Vitamin D ◽  
Antimicrobial Activity ◽  
Parathyroid Hormone ◽  
Pilot Study ◽  
Serum Levels ◽  
Blood Levels ◽  
Healthy Controls ◽  
Icu Patients ◽  
The Impact

It has been recognised that vitamin D (VitD) has a potential role in the regulation of inflammation and protection from infection. In a prospective clinical observational pilot study, we investigated the serum levels of 25-hydroxyvitamin-D3 (25(OH D3), 1,25-hydroxyvitamin-D3 (1,25(OH)2D3), parathyroid hormone (PTH), and cathelicidin in intensive care unit (ICU) patients with or without systemic inflammatory response syndrome (SIRS). We included 32 patients with SIRS (septic patients), 16 ICU patients without SIRS, and 16 healthy controls. To substantiate the findings of the clinical study, we stimulated monocyte-derived macrophages with microbial patterns and analysed the impact of VitD on release of cytokines and antimicrobial activity. We found that patients with or without SIRS had relatively low levels of 25(OH)D3 and 1,25(OH)2D3. Patients with sepsis had significantly lower levels of 25(OH)D3 as compared to ICU control patients and healthy controls (10.53 ± 11.3 μg/l versus 16.46 ± 12.58 μg/l versus 24.04 ± 12.07 μg/l); the same was true for 1,25(OH)2D3. Serum levels of PTH and cathelicidin were significantly increased in sepsis patients, as compared to the other groups. In vitro, VitD significantly decreased the release of pro-inflammatory cytokines from macrophages and increased the antimicrobial activity of the cells. We concluded that patients with sepsis have significantly lower VitD levels. In vitro, VitD modulates inflammation and increases the antibacterial activity of innate immune cells. These findings suggest that VitD insufficiency is mechanistically related to increased susceptibility to SIRS and sepsis.

scholarly journals Influence of chronotype on daily mood fluctuations: pilot study in patients with depression

BJPsych Open ◽  
2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Konstantin F. Brückmann ◽  
Jürgen Hennig ◽  
Matthias J. Müller ◽  
Stanislava Fockenberg ◽  
Anne-Marthe Schmidt ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pilot Study ◽  
Negative Affect ◽  
Clinical Setting ◽  
Early Morning ◽  
Healthy Controls ◽  
Patient Subgroup ◽  
Depression Risk ◽  
Gender And Age ◽  
The Relationship

Summary Depression risk is associated with a late chronotype pattern often described as an ‘evening chronotype’. Fluctuations in mood over consecutive days have not yet been measured according to chronotype in in-patients with depression. A total of 30 in-patients with depression and 32 healthy controls matched for gender and age completed a chronotype questionnaire and twice-daily ratings on mood for 10 consecutive days (registered in the German Clinical Trials Register: DRKS00010215). The in-patients had Saturdays and Sundays as hospital-leave days. The relationship between chronotype and daily mood was mediated by the weekday–weekend schedule with higher levels of negative affect in the evening-chronotype patient subgroup at weekends. Results are discussed with respect to a probably advantageous standardised clinical setting with early morning routines, especially for patients with evening chronotypes.

scholarly journals The inflammatory profile of cerebrospinal fluid, plasma, and saliva from patients with severe neuropathic pain and healthy controls-a pilot study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mika Jönsson ◽  
Björn Gerdle ◽  
Bijar Ghafouri ◽  
Emmanuel Bäckryd
Keyword(s):  
Cerebrospinal Fluid ◽  
Neuropathic Pain ◽  
Pain Intensity ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Partial Least Square Regression ◽  
Therapeutic Interventions ◽  
Healthy Controls ◽  
Inflammatory Profile

Abstract Background Neuropathic pain (NeuP) is a complex, debilitating condition of the somatosensory system, where dysregulation between pro- and anti-inflammatory cytokines and chemokines are believed to play a pivotal role. As of date, there is no ubiquitously accepted diagnostic test for NeuP and current therapeutic interventions are lacking in efficacy. The aim of this study was to investigate the ability of three biofluids - saliva, plasma, and cerebrospinal fluid (CSF), to discriminate an inflammatory profile at a central, systemic, and peripheral level in NeuP patients compared to healthy controls. Methods The concentrations of 71 cytokines, chemokines and growth factors in saliva, plasma, and CSF samples from 13 patients with peripheral NeuP and 13 healthy controls were analyzed using a multiplex-immunoassay based on an electrochemiluminescent detection method. The NeuP patients were recruited from a clinical trial of intrathecal bolus injection of ziconotide (ClinicalTrials.gov identifier NCT01373983). Multivariate data analysis (principal component analysis and orthogonal partial least square regression) was used to identify proteins significant for group discrimination and protein correlation to pain intensity. Proteins with variable influence of projection (VIP) value higher than 1 (combined with the jack-knifed confidence intervals in the coefficients plot not including zero) were considered significant. Results We found 17 cytokines/chemokines that were significantly up- or down-regulated in NeuP patients compared to healthy controls. Of these 17 proteins, 8 were from saliva, 7 from plasma, and 2 from CSF samples. The correlation analysis showed that the most important proteins that correlated to pain intensity were found in plasma (VIP > 1). Conclusions Investigation of the inflammatory profile of NeuP showed that most of the significant proteins for group separation were found in the less invasive biofluids of saliva and plasma. Within the NeuP patient group it was also seen that proteins in plasma had the highest correlation to pain intensity. These preliminary results indicate a potential for further biomarker research in the more easily accessible biofluids of saliva and plasma for chronic peripheral neuropathic pain where a combination of YKL-40 and MIP-1α in saliva might be of special interest for future studies that also include other non-neuropathic pain states.

scholarly journals Metabolomics for Biomarker Discovery: Key Signatory Metabolic Profiles for the Identification and Discrimination of Oat Cultivars

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 165
Author(s):  
Chanel J. Pretorius ◽  
Fidele Tugizimana ◽  
Paul A. Steenkamp ◽  
Lizelle A. Piater ◽  
Ian A. Dubery
Keyword(s):  
High Performance ◽  
Biomarker Discovery ◽  
Cultivar Identification ◽  
Principal Component ◽  
Rapid Identification ◽  
Maturity Stage ◽  
Metabolic Profiles ◽  
High Definition ◽  
Metabolic Markers ◽  
Leaves And Roots

The first step in crop introduction—or breeding programmes—requires cultivar identification and characterisation. Rapid identification methods would therefore greatly improve registration, breeding, seed, trade and inspection processes. Metabolomics has proven to be indispensable in interrogating cellular biochemistry and phenotyping. Furthermore, metabolic fingerprints are chemical maps that can provide detailed insights into the molecular composition of a biological system under consideration. Here, metabolomics was applied to unravel differential metabolic profiles of various oat (Avena sativa) cultivars (Magnifico, Dunnart, Pallinup, Overberg and SWK001) and to identify signatory biomarkers for cultivar identification. The respective cultivars were grown under controlled conditions up to the 3-week maturity stage, and leaves and roots were harvested for each cultivar. Metabolites were extracted using 80% methanol, and extracts were analysed on an ultra-high performance liquid chromatography (UHPLC) system coupled to a quadrupole time-of-flight (qTOF) high-definition mass spectrometer analytical platform. The generated data were processed and analysed using multivariate statistical methods. Principal component analysis (PCA) models were computed for both leaf and root data, with PCA score plots indicating cultivar-related clustering of the samples and pointing to underlying differential metabolic profiles of these cultivars. Further multivariate analyses were performed to profile differential signatory markers, which included carboxylic acids, amino acids, fatty acids, phenolic compounds (hydroxycinnamic and hydroxybenzoic acids, and associated derivatives) and flavonoids, among the respective cultivars. Based on the key signatory metabolic markers, the cultivars were successfully distinguished from one another in profiles derived from both leaves and roots. The study demonstrates that metabolomics can be used as a rapid phenotyping tool for cultivar differentiation.

scholarly journals 1H NMR-Based Analysis of Serum Metabolites in Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Taijie Lin ◽  
Jinping Gu ◽  
Caihua Huang ◽  
Suli Zheng ◽  
Xu Lin ◽  
...  
Keyword(s):  
Intraperitoneal Injection ◽  
Ventricular Hypertrophy ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Metabolic Profiles ◽  
Metabolic Dysfunction ◽  
Sprague Dawley ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Aims. To study the changes of the metabolic profile during the pathogenesis in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH).Methods. Forty male Sprague-Dawley (SD) rats were randomly divided into 5 groups (n=8, each). PAH rats were induced by a single dose intraperitoneal injection of 60 mg/kg MCT, while 8 rats given intraperitoneal injection of 1 ml normal saline and scarified in the same day (W0) served as control. Mean pulmonary arterial pressure (mPAP) was measured through catherization. The degree of right ventricular hypertrophy and pulmonary hyperplasia were determined at the end of first to fourth weeks; nuclear magnetic resonance (NMR) spectra of sera were then acquired for the analysis of metabolites. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to discriminate different metabolic profiles.Results. The prominent changes of metabolic profiles were seen during these four weeks. Twenty specific metabolites were identified, which were mainly involved in lipid metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism. Profiles of correlation between these metabolites in each stage changed markedly, especially in the fourth week. Highly activated methionine and betaine metabolism pathways were selected by the pathway enrichment analysis.Conclusions. Metabolic dysfunction is involved in the development and progression of PAH.

scholarly journals Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Huan-Hua Xu ◽  
Zhen-Hong Jiang ◽  
Cong-Shu Huang ◽  
Yu-Ting Sun ◽  
Long-Long Xu ◽  
...  
Keyword(s):  
Chemical Properties ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Practical Significance ◽  
Plasma Metabolites ◽  
Active Components ◽  
The Difference

Abstract Background OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI. Methods Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. Results Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism. Conclusions This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.

scholarly journals Case-Control Pilot Study of Soft Contact Lens Wearers With Corneal Infiltrative Events and Healthy Controls

2016 ◽  
Vol 57 (1) ◽  
pp. 47 ◽  
Author(s):  
Kathryn Richdale ◽  
Dawn Y. Lam ◽  
Heidi Wagner ◽  
Aaron B. Zimmerman ◽  
Beth T. Kinoshita ◽  
...  
Keyword(s):  
Pilot Study ◽  
Contact Lens ◽  
Case Control ◽  
Healthy Controls ◽  
Soft Contact ◽  
Soft Contact Lens

scholarly journals Monitoring Migraine Cycle Dynamics with an Easy-to-Use Electrophysiological Marker—A Pilot Study

Sensors ◽  
2018 ◽  
Vol 18 (11) ◽  
pp. 3918 ◽  
Author(s):  
Goded Shahaf ◽  
Pora Kuperman ◽  
Yuval Bloch ◽  
Shahak Yariv ◽  
Yelena Granovsky
Keyword(s):  
Pilot Study ◽  
Stress Level ◽  
Event Related Potentials ◽  
Healthy Controls ◽  
Preliminary Results ◽  
Auditory Oddball ◽  
Control Subjects ◽  
Related Potentials ◽  
Auditory Oddball Task ◽  
The Brain

Migraine attacks can cause significant discomfort and reduced functioning for days at a time, including the pre-ictal and post-ictal periods. During the inter-ictsal period, however, migraineurs seem to function normally. It is puzzling, therefore, that event-related potentials of migraine patients often differ in the asymptomatic and inter-ictal period. Part of the electrophysiological dynamics demonstrated in the migraine cycle are attention related. In this pilot study we evaluated an easy-to-use new marker, the Brain Engagement Index (BEI), for attention monitoring during the migraine cycle. We sampled 12 migraine patients for 20 days within one calendar month. Each session consisted of subjects’ reports of stress level and migraine-related symptoms, and a 5 min EEG recording, with a 2-electrode EEG device, during an auditory oddball task. The first minute of the EEG sample was analyzed. Repetitive samples were also obtained from 10 healthy controls. The brain engagement index increased significantly during the pre-ictal (p ≈ 0.001) and the ictal (p ≈ 0.020) periods compared with the inter-ictal period. No difference was observed between the pre-ictal and ictal periods. Control subjects demonstrated intermediate Brain Engagement Index values, that is, higher than inter-ictal, yet lower than pre-ictal. Our preliminary results demonstrate the potential advantage of the use of a simple EEG system for improved prediction of migraine attacks. Further study is required to evaluate the efficacy of the Brain Engagement Index in monitoring the migraine cycle and the possible effects of interventions.

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