Cerebrovascular reactivity over time course in healthy subjects

Abstract For the prognosis of stroke, patients with moyamoya disease (MMD) require the estimation of remaining cerebrovascular reactivity. For this purpose, CO2-triggered BOLD fMRI by use of short breath-hold periods seems to be a highly available alternative to nuclear medicine methods. Too long breath-hold periods are difficult to perform, too short breath-hold periods do not lead to sufficient BOLD signal changes. We aimed to investigate the required minimum breath-hold duration to detect distinct BOLD signals in the tissue of healthy subjects to find out how long the minimum breath-hold duration in clinical diagnostics of MMD should be. A prospective study was performed. Fourteen healthy subjects underwent fMRI during end-expiration breath-hold periods of different duration (3, 6, 9, and 12 s). Additionally, we compared the influence of paced and self-paced breathing altering the breath-hold periods. Data of a patient with MMD was evaluated to investigate whether the tested procedure is suitable for clinical use. Significant global BOLD signal increases were detected after breath-hold periods of 6, 9, and 12 s. The signals were significantly higher after breath-hold periods of 9 s than after 6 s, while not when the duration was extended from 9 to 12 s. Furthermore, we found additional BOLD signal changes before the expected signal increases, which could be avoided by paced respiratory instructions. This investigation indicates that end-expiration breath-hold period of at least 9 s might be used to measure the cerebrovascular reactivity. This time period resulted in distinct BOLD signal changes and could be performed easily.

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Jonckheere–Terpstra–Kendall-based non-parametric analysis of temporal differential gene expression

NAR Genomics and Bioinformatics ◽

10.1093/nargab/lqab021 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Hitoshi Iuchi ◽

Michiaki Hamada

Keyword(s):

Gene Expression ◽

Time Series ◽

Time Course ◽

Time Series Data ◽

Expression Patterns ◽

Detection Methods ◽

Series Data ◽

Expression Levels ◽

Over Time ◽

Non Parametric

Abstract Time-course experiments using parallel sequencers have the potential to uncover gradual changes in cells over time that cannot be observed in a two-point comparison. An essential step in time-series data analysis is the identification of temporal differentially expressed genes (TEGs) under two conditions (e.g. control versus case). Model-based approaches, which are typical TEG detection methods, often set one parameter (e.g. degree or degree of freedom) for one dataset. This approach risks modeling of linearly increasing genes with higher-order functions, or fitting of cyclic gene expression with linear functions, thereby leading to false positives/negatives. Here, we present a Jonckheere–Terpstra–Kendall (JTK)-based non-parametric algorithm for TEG detection. Benchmarks, using simulation data, show that the JTK-based approach outperforms existing methods, especially in long time-series experiments. Additionally, application of JTK in the analysis of time-series RNA-seq data from seven tissue types, across developmental stages in mouse and rat, suggested that the wave pattern contributes to the TEG identification of JTK, not the difference in expression levels. This result suggests that JTK is a suitable algorithm when focusing on expression patterns over time rather than expression levels, such as comparisons between different species. These results show that JTK is an excellent candidate for TEG detection.

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Decomposition of Growth Curves into Growth Rate and Acceleration: a Novel Procedure to Monitor Bacterial Growth and the Time-Dependent Effect of Antimicrobials

Applied and Environmental Microbiology ◽

10.1128/aem.01849-21 ◽

2021 ◽

Author(s):

M. Luisa Navarro-Pérez ◽

M. Coronada Fernández-Calderón ◽

Virginia Vadillo-Rodríguez

Keyword(s):

Growth Rate ◽

Mathematical Models ◽

Bacterial Growth ◽

Time Course ◽

Antimicrobial Agents ◽

Numerical Procedure ◽

Growth Curves ◽

Predictive Microbiology ◽

Insight Into ◽

Over Time

In this paper, a simple numerical procedure is presented to monitor the growth of Streptococcus sanguinis over time in the absence and presence of propolis, a natural antimicrobial. In particular, it is shown that the real-time decomposition of growth curves obtained through optical density measurements into growth rate and acceleration can be a powerful tool to precisely assess a large range of key parameters [ i.e. lag time ( t 0 ), starting growth rate ( γ 0 ), initial acceleration of the growth ( a 0 ), maximum growth rate ( γ max ), maximum acceleration ( a max ) and deceleration ( a min ) of the growth and the total number of cells at the beginning of the saturation phase ( N s )] that can be readily used to fully describe growth over time. Consequently, the procedure presented provides precise data of the time course of the different growth phases and features, which is expected to be relevant, for instance, to thoroughly evaluate the effect of new antimicrobial agents. It further provides insight into predictive microbiology, likely having important implications to assumptions adopted in mathematical models to predict the progress of bacterial growth. Importance: The new and simple numerical procedure presented in this paper to analyze bacterial growth will possibly allow identifying true differences in efficacy among antimicrobial drugs for their applications in human health, food security, and environment, among others. It further provides insight into predictive microbiology, likely helping in the development of proper mathematical models to predict the course of bacterial growth under diverse circumstances.

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Recovery of subjective visual horizontal after unilateral vestibular deafferentation by intratympanic instillation of gentamicin

Journal of Vestibular Research ◽

10.3233/ves-2006-161-207 ◽

2006 ◽

Vol 16 (1-2) ◽

pp. 69-73 ◽

Cited By ~ 4

Author(s):

Yoshinari Takai ◽

Toshihisa Murofushi ◽

Munetaka Ushio ◽

Shinichi Iwasaki

Keyword(s):

Healthy Subjects ◽

Time Course ◽

Early Stage ◽

Ccd Camera ◽

The Other ◽

Spontaneous Nystagmus ◽

Vestibular Evoked Myogenic Potentials ◽

Normal Range ◽

Intratympanic Gentamicin ◽

Unilateral Vestibular Deafferentation

The time course of the recovery of subjective visual horizontal (SVH) after unilateral vestibular deafferentation by intratympanic instillation of gentamicin was studied. Six patients who underwent intratympanic gentamicin instillation therapy for Meniere's disease (1 man and 5 women, 32 to 69 years of age) were enrolled in this study. For comparison, SVH in 23 healthy subjects (12 men and 11 woman, 23 to 48 years of age) was also measured. The mean ± SD of SVH in healthy subjects was 0.0 ± 1.1 deg. All of the 6 patients showed significantly deviated SVH toward the injected side-down at the early stage after the therapy. Although one patient showed recovery of SVH to the normal range 25 days after the injection, the other patients required more time for recovery. Three patients did not show recovery to the normal range after 1 year. On the other hand, spontaneous nystagmus observed using an infrared CCD camera in total dark disappeared after 35 days (median). Patients who had normal vestibular evoked myogenic potentials before the therapy showed a tendency of delay of recovery of SVH. The reasons why the recovery of SVH took longer than the disappearance of spontaneous nystagmus are discussed in this report.

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Sleep Disorder Over Time: Psychiatric Correlates Among Males

The British Journal of Psychiatry ◽

10.1192/bjp.136.5.456 ◽

1980 ◽

Vol 136 (5) ◽

pp. 456-462 ◽

Cited By ~ 15

Author(s):

Hervey Sweetwood ◽

Igor Grant ◽

Daniel F. Kripke ◽

Marvin S. Gerst ◽

Joel Yager

Keyword(s):

Prospective Study ◽

Sleep Disorder ◽

Sleep Disturbances ◽

Time Course ◽

Psychiatric Symptomatology ◽

Over Time

SummaryThis 18 month prospective study assessed the time course of sleep disturbances in 85 male psychiatric out-patients and 103 male non-patients. Over one-third of the patients and 5 per cent of the non-patients reported frequent symptoms of insomnia during at least 14 of the 18 months. Frequency and chronicity of insomnia were strongly associated with intensity of psychiatric symptomatology, but not with diagnosis. Minor tranquillizers and hypnotics were used frequently by patients and occasionally by non-patients, but there was little indication that they altered the course of insomnia.

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Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells

Clinical and Molecular Allergy ◽

10.1186/s12948-021-00163-8 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Noelle Zurmühl ◽

Anna Schmitt ◽

Ulrike Formentini ◽

Johannes Weiss ◽

Heike Appel ◽

...

Keyword(s):

Dendritic Cells ◽

Healthy Subjects ◽

Time Course ◽

In Vitro Study ◽

Allergic Diseases ◽

Plasmacytoid Dendritic Cells ◽

Antigen Uptake ◽

Der P 1 ◽

The Impact

Abstract Background Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. Methods This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. Results We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. Conclusions To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.

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Predicting context specific enhancer-promoter interactions from ChIP-Seq time course data

10.7287/peerj.preprints.3093 ◽

2017 ◽

Author(s):

Tomasz Dzida ◽

Mudassar Iqbal ◽

Iryna Charapitsa ◽

George Reid ◽

Henk Stunnenberg ◽

...

Keyword(s):

Estrogen Receptor Alpha ◽

Time Course ◽

Target Genes ◽

Mcf7 Cells ◽

Genome Wide ◽

A Genome ◽

Machine Learning Approach ◽

Protein Occupancy ◽

Context Specific ◽

Over Time

We have developed a machine learning approach to predict context specific enhancer-promoter interactions using evidence from changes in genomic protein occupancy over time. The occupancy of estrogen receptor alpha (ERα), RNA polymerase (Pol II) and histone marks H2AZ and H3K4me3 were measured over time using ChIP-Seq experiments in MCF7 cells stimulated with estrogen. A Bayesian classifier was developed which uses the correlation of temporal binding patterns at enhancers and promoters and genomic proximity as features to predict interactions. This method was trained using experimentally determined interactions from the same system and was shown to achieve much higher precision than predictions based on the genomic proximity of nearest ERα binding. We use the method to identify a genome-wide confident set of ERα target genes and their regulatory enhancers genome-wide. Validation with publicly available GRO-Seq data demonstrates that our predicted targets are much more likely to show early nascent transcription than predictions based on genomic ERα binding proximity alone.

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Changes in Nitric Oxide Releases of the Contralateral Acupoint during and after Laser Acupuncture at Bilateral Same-Name Acupoints in Human

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/5763458 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Wan-Ling Jiang ◽

Hua-Jiang Wei ◽

Zhou-Yi Guo ◽

Yi-Rong Ni ◽

Hong-Qin Yang ◽

...

Keyword(s):

Nitric Oxide ◽

Healthy Subjects ◽

Vessel Wall ◽

Time Course ◽

Contralateral Side ◽

Control Area ◽

Laser Acupuncture ◽

Blinded Fashion ◽

No Release ◽

No Releases

Objective.The purpose of the study was to examine the effects of laser acupuncture (LA) at right Neiguan (RPC6)/left Neiguan (LPC6) acupoints on the releases of nitric oxide (NO) in the treated and contralateral/nontreated PC6, compared to the nonacupoint control area.Methods. 24 mW LA at RPC6, LPC6, and nonacupoint in 22 healthy subjects for 40 min: sterilized dialysis tube was taped to the nontreated PC6/nonacupoint during the treatment and immediately taped to the treated and nontreated PC6/nonacupoint after LA removal. NO-scavenging compound was injected into the tube for 40 min to absorb the molecular which was tested by spectrophotometry in a blinded fashion.Results. LA-induced NO releases over PC6 acupoints for the nontreated and treated sides all significantly increased after LA removal, but for the nontreated acupoints they did not change during LA stimulation. LA at RPC6 induced the more release of the NO at contralateral side than stimulating LPC6, but not on nonacupoints. The results suggest that LA-induced NO release over contralateral acupoint and NO release resulting from the lateralized specificity all are different and specific to the acupoint within different time course.Conclusions. LA-evoked NO release over acupoints could improve the neurogenic, endothelial activity of the vessel wall to further facilitate microcirculation.

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AB1239 THE EFFECT OF INFLUENZA VACCINATION ON THE MULTI-BIOMARKER DISEASE ACTIVITY SCORE AND ITS COMPONENT BIOMARKERS IN HEALTHY SUBJECTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1188 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1910-1911

Author(s):

D. Furst ◽

L. Lenz ◽

M. Horton ◽

D. Flake ◽

E. Sasso ◽

...

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Disease Activity ◽

Virus Vaccine ◽

Healthy Subjects ◽

Influenza Virus Vaccine ◽

National Institutes Of Health ◽

Research Support ◽

Myriad Genetics ◽

Over Time

Background:The multi-biomarker disease activity (MBDA) blood test measures 12 protein biomarkers (IL-6, CRP, SAA, EGF, VEGF, VCAM, MMP-1, MMP-3, leptin, resistin, TNF-RI and YKL40). It uses a validated algorithm to provide a score on a scale of 1-100 for assessing disease activity in patients with rheumatoid arthritis (RA). The MBDA score reflects several molecular aspects of inflammation, including cytokines, acute phase reactants, growth factors, molecular adhesion, metalloproteinases and hormones. Insights gained by understanding how vaccination affects these biomarkers in healthy subjects - in whom the level of inflammation prior to vaccination should be low and stable - may aid the understanding of how vaccination affects patients with RA.Objectives:The goal of this study was to understand how immunization of healthy subjects with the influenza vaccine affects the assessment of inflammation with the MBDA score and its 12 biomarkers.Methods:A 4-strain influenza virus vaccine (Fluarix Quadrivalent, GlaxoSmithKline) was administered intramuscularly to 22 healthy volunteer subjects on October 24, 2018. Serum samples were obtained immediately prior to vaccination (baseline) and 1, 2 and 3 weeks after vaccination. No restrictions were placed on subject activity. Samples were stored at -80oC until measurement of the 12 MBDA biomarkers for determination of the adjusted MBDA score, hereafter called the MBDA score. (Adjustment accounts for the effects of age, sex and adiposity1). MBDA scores (natural scale) and biomarker concentrations (log scale) were modeled using generalized estimating equations (GEE) that account for correlations between measurements from the same subject at multiple timepoints. Significance of MBDA score change or biomarker concentration change over time was determined by a likelihood ratio test of timepoints.Results:Of the 22 healthy subjects receiving the influenza virus vaccine, 14 (63.6%) were female, with mean (SD) age of 40.0 years (8.9). MBDA scores were low (<30), moderate (30-44) or high (>44) for 15 (68%), 6 (27%) and 1 (5%) subjects at baseline, and this distribution was stable over time (Figure 1). Overall, MBDA scores did not change significantly over time (p=0.48, Figure 2). Mean changes in MBDA score (95% CI) from baseline to weeks 1, 2 and 3 were 0.32 (-3.07, 3.71), 0.82 (-3.03, 4.67) and 2.86 (-1.10, 6.82), respectively (Figure 2); the week 3 value becomes 0.95 (-1.78, 3.68) if the week 3 outlier is removed. Among the 66 post-baseline measurements of change in MBDA score (Figure 2), 3 (5%) exceeded the 95% CI for change in MBDA score in this study (i.e., 14). When assessing the entire cohort across all timepoints, EGF was the only biomarker that demonstrated statistically significant change over time (p=5.6 x 10-7). At weeks 1, 2 and 3, the mean relative concentrations of EGF, compared with baseline, were 0.62 (0.52, 0.74), 0.86 (0.70, 1.06) and 0.62 (0.50, 0.76), respectively.Figure 1Figure 2Conclusion:Immunization of 22 healthy subjects with a quadrivalent influenza vaccine did not have a statistically significant effect on MBDA scores during a 3-week observation, and it had minimal effect on the component biomarkers.References:[1]Curtis et al.Rheumatology [Oxford]2018;58:874Disclosure of Interests:Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company), Lauren Lenz Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Megan Horton Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Darl Flake Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Eric Sasso Shareholder of: Myriad Genetics, Inc., Employee of: Myriad Genetics, Inc., Michael E. Weinblatt Grant/research support from: BMS, Amgen, Lilly, Crescendo and Sonofi-Regeneron, Consultant of: Horizon Therapeutics, Bristol-Myers Squibb, Amgen, Abbvie, Crescendo, Lilly, Pfizer, Roche, Gilead

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