Application of PBPK model for coproporphyrin I to evaluate the impact of SLCO1B1 genotype, ethnicity, and sex on its inter‐individual variability

Clinical Pharmacokinetic Studies in Pregnant Women and the Relevance of Pharmacometric Tools

Current Pharmaceutical Design ◽

10.2174/1381612825666190320135137 ◽

2019 ◽

Vol 25 (5) ◽

pp. 483-495 ◽

Cited By ~ 7

Author(s):

André Dallmann ◽

Paola Mian ◽

Johannes Van den Anker ◽

Karel Allegaert

Keyword(s):

Pregnant Women ◽

Clinical Pharmacokinetic ◽

Individual Variability ◽

Current Status ◽

Pharmacokinetic Studies ◽

Full Potential ◽

Pbpk Models ◽

Pregnancy And Postpartum ◽

Population Pk ◽

The Impact

Background: In clinical pharmacokinetic (PK) studies, pregnant women are significantly underrepresented because of ethical and legal reasons which lead to a paucity of information on potential PK changes in this population. As a consequence, pharmacometric tools became instrumental to explore and quantify the impact of PK changes during pregnancy. Methods: We explore and discuss the typical characteristics of population PK and physiologically based pharmacokinetic (PBPK) models with a specific focus on pregnancy and postpartum. Results: Population PK models enable the analysis of dense, sparse or unbalanced data to explore covariates in order to (partly) explain inter-individual variability (including pregnancy) and to individualize dosing. For population PK models, we subsequently used an illustrative approach with ketorolac data to highlight the relevance of enantiomer specific modeling for racemic drugs during pregnancy, while data on antibiotic prophylaxis (cefazolin) during surgery illustrate the specific characteristics of the fetal compartments in the presence of timeconcentration profiles. For PBPK models, an overview on the current status of reports and papers during pregnancy is followed by a PBPK cefuroxime model to illustrate the added benefit of PBPK in evaluating dosing regimens in pregnant women. Conclusions: Pharmacometric tools became very instrumental to improve perinatal pharmacology. However, to reach their full potential, multidisciplinary collaboration and structured efforts are needed to generate more information from already available datasets, to share data and models, and to stimulate cross talk between clinicians and pharmacometricians to generate specific observations (pathophysiology during pregnancy, breastfeeding) needed to further develop the field.

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The Impact of Personality Disorders on Longitudinal Change in Relationship Satisfaction in Long-Term Married Couples

Journal of Personality Disorders ◽

10.1521/pedi_2019_33_392 ◽

2020 ◽

Vol 34 (4) ◽

pp. 439-458 ◽

Cited By ~ 1

Author(s):

Susan C. South ◽

Michael J. Boudreaux ◽

Thomas F. Oltmanns

Keyword(s):

Marital Satisfaction ◽

Relationship Satisfaction ◽

Personality Disorders ◽

Married Couples ◽

Structured Interview ◽

Individual Variability ◽

Self Report ◽

Longitudinal Change ◽

The Impact

Personality disorders (PDs) are significantly, negatively related to marital satisfaction. We examine how maladaptive personality is related to change in marital satisfaction over time utilizing data from the St. Louis Personality and Aging Network (SPAN), a longitudinal, community-based study of personality and health in older adults. Participants were assessed at baseline for PD (self-report, informant-report, and structured interview); self- and spouse-reported relationship satisfaction assessed at baseline and five follow-ups was analyzed with latent growth curve modeling. Higher levels of PD at baseline were associated with lower self and spouse relationship satisfaction at baseline. On average, satisfaction did not change significantly over the study period, but there was significant individual variability. Higher levels of schizoid PD were protective of declines in partner's perception of satisfaction. Findings suggest that partners in long-term married unions may have adapted to the presence of their own or their spouse's level of personality pathology.

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European beech is a net annual source of methane (CH4)

10.5194/egusphere-egu21-4335 ◽

2021 ◽

Author(s):

Katerina Machacova ◽

Hannes Warlo ◽

Kateřina Svobodová ◽

Thomas Agyei ◽

Tereza Uchytilová ◽

...

Keyword(s):

Greenhouse Gas ◽

Seasonal Dynamics ◽

Forest Floor ◽

Greenhouse Gas Emission ◽

European Beech ◽

Individual Variability ◽

Spatiotemporal Variability ◽

Vegetation Season ◽

Dormant Season ◽

The Impact

Trees are known to be sources of methane (CH4), an important greenhouse gas, into the atmosphere. However, still little is known about the seasonality of the tree stem CH4 fluxes, particularly for the dormant season, and about the impact of environmental parameters on this gas exchange. This makes the estimation of net annual ecosystem CH4 fluxes difficult.We determined seasonal dynamics of CH4 exchange of mature European beech stems (Fagus sylvatica) and of adjacent forest floor in a temperate montane forest of White Carpathians, Czech Republic, from November 2017 to December 2018. We used static chamber methods and gas chromatographic analyses. We aimed to understand the unknown role in seasonal changes of CH4 fluxes of these forests, and the spatiotemporal variability of the tree fluxes.The beech stems were net annual sources for atmospheric CH4, whereas the forest floor was a predominant sink for CH4. The stem CH4 emissions showed high inter-individual variability and clear seasonality following the stem CO2 efflux. The fluxes of CH4 peaked during the vegetation season, and remained low but significant to the annual totals during winter dormancy. By contrast, the forest floor CH4 uptake followed an opposite flux trend with low CH4 uptake detected in the winter dormant season and elevated CH4 uptake during the vegetation season. Based on our preliminary analyses, the detected high spatial variability in stem CH4 emissions can be explained neither by the CH4 exchange at the forest floor level, nor by soil CH4 concentrations, soil water content and soil temperature, all measured in vertical soil profiles close to the studied trees.European beech trees, native and widely spread species of Central Europe, seem to markedly contribute to the seasonal dynamics of the ecosystem CH4 exchange, and their CH4 fluxes should be included into forest greenhouse gas emission inventories.&#160;AcknowledgementThis research was supported by the Czech Science Foundation (17-18112Y), National Programme for Sustainability I (LO1415), CzeCOS (LM2015061), and SustES - Adaptation strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/0000797). We thank Libor Bor&#225;k and Leszek Dariusz Laptaszy&#324;ski for their technical and field support.&#160;

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Multidimensional aspects related to shiftworkers' health and well-being

Revista de Saúde Pública ◽

10.1590/s0034-89102004000700013 ◽

2004 ◽

Vol 38 (suppl) ◽

pp. 86-91 ◽

Cited By ~ 15

Author(s):

Giovanni Costa

Keyword(s):

Family Relations ◽

Biological Rhythms ◽

Well Being ◽

Individual Variability ◽

Human Dimensions ◽

Individual Characteristics ◽

Social Conditions ◽

Specific Work ◽

The Impact ◽

Health And Well Being

The impact of shift and night work on health shows a high inter- and intra-individual variability, both in terms of kind of troubles and temporal occurrence, related to various intervening factors dealing with individual characteristics, lifestyles, work demands, company organisation, family relations and social conditions. The way we define "health" and "well-being" can significantly influence appraisals, outcomes and interventions. As the goal is the optimisation of shiftworkers' health, it is necessary to go beyond the health protection and to act for health promotion. In this perspective, not only people related to medical sciences, but many other actors (ergonomists, psychologists, sociologists, educators, legislators), as well as shiftworkers themselves. Many models have been proposed aimed at describing the intervening variables mediating and/or moderating the effects; they try to define the interactions and the pathways connecting risk factors and outcomes through several human dimensions, which refer to physiology, psychology, pathology, sociology, ergonomics, economics, politics, and ethics. So, different criteria can be used to evaluate shiftworkers' health and well-being, starting from biological rhythms and ending in severe health disorders, passing through psychological strain, job dissatisfaction, family perturbation and social dis-adaptation, both in the short- and long-term. Consequently, it appears rather arbitrary to focus the problem of shiftworkers' health and tolerance only on specific aspects (e.g. individual characteristics), but a systemic approach appears more appropriate, able to match as many variables as possible, and aimed at defining which factors are the most relevant for those specific work and social conditions. This can support a more effective and profitable (for individuals, companies, and society) adoption of preventive and compensative measures, that must refer more to "countervalues" rather than to "counterweights".

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Komunitas Masyarakat Dan Perawatan Kesehatan Dalam Peningkatan Kualitas Hidup

DINAMIKA KESEHATAN JURNAL KEBIDANAN DAN KEPERAWATAN ◽

10.33859/dksm.v10i1.437 ◽

2020 ◽

Vol 10 (1) ◽

pp. 11-24

Author(s):

Agustinus Hermino

Keyword(s):

Quality Of Life ◽

Health Care ◽

Health Care Quality ◽

Health Sector ◽

Well Being ◽

Individual Variability ◽

Care Quality ◽

Global Era ◽

The Impact

Latar belakang: Seiring dengan perkembangan jaman, dalam beberapa tahun terakhir ini banyak perhatian yang difokuskan pada eksplorasi dampak penyakit fisik dan mental pada kualitas hidup seseorang baik secara individu maupun masyarakat secara keseluruhan. Sifat subyektif dari 'kualitas hidup' individu, merupakan konsep yang dinamis untuk diukur dan didefinisikan, tetapi bahwa secara umum dapat dipandang sebagai konsep multidimensi yang menekankan pada persepsi diri dari keadaan pikiran seseorang saat iniTujuan: penulisan ini bertujuan untuk memberikan pemahaman tentang peran masyarakat dalam memahani pentingnya kesehatan di era global ditinjau dari perspektif akademis. Pada sektor kesehatan pemahaman kesehatan menjadi sangat pentingnya karena akan menunjukkan pada kualitas hidup seseorang, tetapi hal ini tidak cukup secara individu karena diperlukan pemahaman secara menyeluruh terhadap masyarakat tentang makna kesehatan dan perawatan kesehatan.Metode: penulisan ilmiah ini adalah dengan melakukan analisa akademis dari dari berbagai sumber rujukan relevan sehingga menemukan makna teoritis baru dalam rangka menjawab tantangan yang terjadi di masyarakat.Hasil: Berdasarkan berbagai sumber rujukan yang ada, dapat disimpulkan bahwa kesehatan merupakan gaya hidup yang bertujuan untuk mencapai kesejahteraan fisik, emosional, intelektual, spiritual, dan lingkungan. Penggunaan langkah-langkah kesehatan dapat meningkatkan stamina, energi, dan harga diri, kemudian meningkatkan kualitas hidup. Dengan demikian maka konsep kesehatan memungkinkan adanya variabilitas individu. Kesehatan dapat dianggap sebagai keseimbangan aspek fisik, emosional, psikologis, sosial dan spiritual dari kehidupan seseorang. Kata kunci: masyarakat, perawatan kesehatan, kualitas hidup Society Community and Health Care in Improving Quality of LifeAbstract Background: Along with the development of the era, in recent years there has been a lot of attention focused on exploring the impact of physical and mental illness on the quality of life of a person both individually and as a whole. The subjective nature of an individual's 'quality of life' is a dynamic concept to measure and define, but that in general can be seen as a multidimensional concept that emphasizes self-perception of one's current state of mindAim: purpose of this study is to provide an understanding the role of community in understanding the importance of health in the global era from an academic perspective. In the health sector understanding of health is very important because it will show the quality of life of a person, but this is not enough individually because a comprehensive understanding of the meaning of health and health care is needed. Method: The method of scientific writing is to carry out academic analysis from various relevant reference sources, and find new theoretical meanings in order to answer the challenges that occur in society. Keyword: Community, Society,Health Care, Quality oflife Resullt : Based on various academic reference, it can be concluded that health is a lifestyle that aims to achieve physical, emotional, intellectual, spiritual, and environmental well-being. The use of health measures can increase stamina, energy, and self-esteem, then improve the quality of life. Thus the concept of health allows for individual variability. Health can be considered as a balance of physical, emotional, psychological, social and spiritual aspects of one's life. Keywords: community, health care, quality of life

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Systemic anti-commensal response to fungi analyzed by flow cytometry is related to gut mycobiome ecology

Microbiome ◽

10.1186/s40168-020-00924-8 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Alicia Moreno-Sabater ◽

Gaelle Autaa ◽

Delphine Sterlin ◽

Amenie Jerbi ◽

Remy Villette ◽

...

Keyword(s):

Flow Cytometry ◽

Alpha Diversity ◽

Fungal Species ◽

Individual Variability ◽

Humoral Immune ◽

Healthy Donors ◽

Significant Difference ◽

Genus Richness ◽

Humoral Responses ◽

The Impact

Abstract Background Interest for the study of gut mycobiota in relation with human health and immune homeostasis has increased in the last years. From this perspective, new tools to study the immune/fungal interface are warranted. Systemic humoral immune responses could reflect the dynamic relationships between gut mycobiota and immunity. Using a novel flow cytometry technology (Fungi-Flow) to determine immunoglobulin (Ig) responses to fungi, we studied the relationships between gut mycobiota and systemic humoral anti-commensal immunity. Results The Fungi-Flow method allows a sensitive and specific measurement of systemic IgG responses against 17 commensal and environmental fungi from the two main divisions; Ascomycota and Basidiomycota. IgG responses exhibited a high inter-individual variability. Anti-commensal IgG responses were contrasted with the relative abundance, alpha-diversity, and intra-genus richness of fungal species in gut mycobiota of twenty healthy donors. Categorization of gut mycobiota composition revealed two differentiated fungal ecosystems. Significant difference of anti-Saccharomyces systemic IgG responses were observed in healthy donors stratified according to the fungal ecosystem colonizing their gut. A positive and significant correlation was observed between the variety of IgG responses against fungal commensals and intestinal alpha-diversity. At the level of intra-genus species richness, intense IgG responses were associated with a low intra-genus richness for known pathobionts, but not commensals. Conclusions Fungi-Flow allows an easy and reliable measure of personalized humoral responses against commensal fungi. Combining sequencing technology with our novel Fungi-Flow immunological method, we propose that there are at least two defined ecosystems in the human gut mycobiome associated with systemic humoral responses. Fungi-Flow opens new opportunities to improve our knowledge about the impact of mycobiota in humoral anti-commensal immunity and homeostasis.

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Parental reports of communicative development at the age of 36 months: The Estonian CDI-III

First Language ◽

10.1177/0142723719887313 ◽

2019 ◽

Vol 40 (1) ◽

pp. 64-83

Author(s):

Tiia Tulviste ◽

Astra Schults

Keyword(s):

Day Care ◽

Parent Report ◽

Individual Variability ◽

Vocabulary Size ◽

Communicative Skills ◽

Communicative Development ◽

Language Difficulties ◽

Parental Reports ◽

Language Measures ◽

The Impact

Parental reports are a widely-used source of information about infants’ and toddlers’ communicative skills, but parent-report instruments valid for children older than 30 months are less known. This study explored individual variability in children’s communicative skills at the age of 3;0 via parental reports using the Estonian (E) CDI-III. The validity of ECDI-III was established through correlations with another parent-report instrument (ECDI-II) and a standardized examiner-administered language assessment (New Reynell Developmental Language Scales; NRDLS). A hundred Estonian-speaking children ( M age = 35.77 months, age range from 34 to 39 months; 20 of them with reported language difficulties) participated in the study. Relations between different communicative skills and the impact of such factors as the child’s gender, maternal and paternal education, reported language difficulties, the number of siblings, and day care attendance on variability in vocabulary size were also considered. The results showed that the ECDI-III components were moderately to strongly associated with each other, with the ECDI-II and NRDLS. Children with reported language difficulties scored lower on all language measures, except for orthographic awareness. Girls, children of more educated mothers, children with older siblings, and those who had attended day care for more months obtained higher vocabulary scores.

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Contribution of Berry Polyphenols to the Human Metabolome

Molecules ◽

10.3390/molecules24234220 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4220 ◽

Cited By ~ 9

Author(s):

Chandra ◽

Rathore ◽

Kay ◽

Everhart ◽

Curtis ◽

...

Keyword(s):

Hippuric Acid ◽

Plant Secondary Metabolites ◽

Individual Variability ◽

Significant Treatment ◽

Quantitative Metabolomics ◽

Background Diet ◽

Hydroxyphenylacetic Acid ◽

The Usa ◽

The Impact ◽

Standard Library

Diets rich in berries provide health benefits, however, the contribution of berry phytochemicals to the human metabolome is largely unknown. The present study aimed to establish the impact of berry phytochemicals on the human metabolome. A “systematic review strategy” was utilized to characterize the phytochemical composition of the berries most commonly consumed in the USA; (poly)phenols, primarily anthocyanins, comprised the majority of reported plant secondary metabolites. A reference standard library and tandem mass spectrometry (MS/MS) quantitative metabolomics methodology were developed and applied to serum/plasma samples from a blueberry and a strawberry intervention, revealing a diversity of benzoic, cinnamic, phenylacetic, 3-(phenyl)propanoic and hippuric acids, and benzyldehydes. 3-Phenylpropanoic, 2-hydroxybenzoic, and hippuric acid were highly abundant (mean > 1 µM). Few metabolites at concentrations above 100 nM changed significantly in either intervention. Significant intervention effects (P < 0.05) were observed for plasma/serum 2-hydroxybenzoic acid and hippuric acid in the blueberry intervention, and for 3-methoxyphenylacetic acid and 4-hydroxyphenylacetic acid in the strawberry intervention. However, significant within-group effects for change from baseline were prevalent, suggesting that high inter-individual variability precluded significant treatment effects. Berry consumption in general appears to cause a fluctuation in the pools of small molecule metabolites already present at baseline, rather than the appearance of unique berry-derived metabolites, which likely reflects the ubiquitous nature of (poly)phenols in the background diet.

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Pupil Function in Pseudophakia: Proximal Miosis Behavior and Optical Influence

Photonics ◽

10.3390/photonics6040114 ◽

2019 ◽

Vol 6 (4) ◽

pp. 114 ◽

Cited By ~ 1

Author(s):

Elsa Fonseca ◽

Paulo Fiadeiro ◽

Renato Gomes ◽

Angel Sanchez Trancon ◽

António Baptista ◽

...

Keyword(s):

Pupil Size ◽

Angular Size ◽

Optical Quality ◽

Individual Variability ◽

Computer Simulation Model ◽

Small Contribution ◽

Distant Object ◽

Object Distance ◽

The Mean ◽

The Impact

The pseudophakic eye lacks the ability to produce a refractive change in response to object proximity. Thus, individual anatomical features such as the pupil size play an important role in achieving functional vision levels. In this work, the range of pupil sizes at varying object distance was measured in pseudophakic participants. Furthermore, the impact of the measured values on eye optical quality was investigated using a computer simulation model. A binocular eye-tracker was used to measure the participants’ pupil sizes at six object distances, ranging from 0.33 m (i.e., vergence of 3.00 D) to 3.00 m (i.e., vergence of 0.33 D), while observing a Maltese cross with a constant angular size of 1 ∘ . In total, 58 pseudophakic participants were enrolled in this study (age mean ± standard deviation: 70.5 ± 11.3 years). The effects of object distance and age on pupil size variation were investigated using linear mixed effects regression models. Age was found to have a small contribution to individual variability. The mean infinite distance pupil size (intercept) was 4.45 ( 95 % CI: 2.74, 6.17) mm and the mean proximal miosis (slope) was − 0.23 ( 95 % CI: −0.53, 0.08) mm/D. The visual acuity (VA) estimation for a distant object ranged from − 0.1 logMAR (smallest pupil) to 0.04 logMAR (largest pupil) and the near VA ( 0.33 m) when mean proximal miosis was considered ranged from 0.28 logMAR (smallest pupil) to 0.42 logMAR (largest pupil). When mean distance pupil was considered, proximal miosis individual variability produced a variation of 0.04 logMAR for the near object and negligible variation for the distant object. These results support the importance of distance pupil size measurement for the prediction of visual performance in pseudophakia, while suggesting that proximal miosis has a negligible impact in VA variability.

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Individual variability and sex differences in conditioned pain modulation and the impact of resilience, and conditioning stimulus pain unpleasantness and salience

Pain ◽

10.1097/j.pain.0000000000001863 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Cited By ~ 2

Author(s):

Shahrzad Firouzian ◽

Natalie R. Osborne ◽

Joshua C. Cheng ◽

Junseok A. Kim ◽

Rachael L. Bosma ◽

...

Keyword(s):

Sex Differences ◽

Conditioning Stimulus ◽

Individual Variability ◽

Pain Modulation ◽

Conditioned Pain Modulation ◽

The Impact ◽

Pain Unpleasantness

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