Interindividual Variations Research Articles

Ionizing Radiation-Induced DNA Damage Response in Primary Melanocytes and Keratinocytes of Human Skin

Currently, our knowledge of how different cell types in a tissue microenvironment respond to low and high linear energy transfer (LET) radiation is highly restricted. In this study, a comparative analysis was performed on γ-ray-induced DNA damage and repair in primary human melanocytes and keratinocytes isolated from 3 donors. Our study demonstrates a modest interindividual variability in both melanocytes and keratinocytes in terms of both spontaneous and ionizing radiation (IR)-induced 53BP1 foci formation and persistence. Melanocytes, in general, showed a slightly elevated (1.66–2.79 folds more) 53BP1 foci induction relative to keratinocytes after exposure to different doses of γ-rays (0.1–2.5 Gy) radiation. To verify the influence of ATM kinase on IR-induced 53BP1 foci formation, melanocytes and keratinocytes were treated with a specific ATM kinase inhibitor (KU55993, 10 μM) for 1 h prior to radiation. ATM kinase inhibition resulted in the reduction of both spontaneous and IR-induced 53BP1 foci by 17–42% in both melanocytes and keratinocytes of all the 3 donors. Increased persistence of IR-induced 53BP1 foci number was observed in ATM-inhibited melanocytes and keratinocytes after different post exposure times (6 h and 24 h). Taken together, our study suggests that interindividual variations exist in the induction and repair of DNA double-strand breaks (DSBs) in melanocytes and keratinocytes and that ATM is crucial for an optimal DSB repair efficiency in both human skin cell types.

Inter-individual responses of post-exercise hypotension in older adults with hypertension: An exploratory analysis of different exercise modalities.

Background: Various physical exercise modalities can acutely reduce blood pressure (BP). However, not all individuals respond similarly after an exercise session. Purpose: To measure inter-individual variations in 24-hBP after a single bout of various exercise modalities in older adults with hypertension. Methods: This retrospective study analyzed data from participants with hypertension (≥60years) previously included in three randomized controlled trials on this topic. BP was assessed using ambulatory BP monitoring. We compared the mean changes in total 24-h, daytime, and nighttime BP after aerobic (AE, n = 19), combined (COMB, n = 19), resistance (RES, n = 23), and isometric handgrip (ISO, n = 18) exercise sessions to a non-exercising control session (C). The minimum detectable changes to classify the participant as a "Responder" for the corresponding exercise protocol were 4 and 2mmHg for systolic and diastolic BP, respectively. Results: The prevalence of Responders for systolic BP was as follows: AE 24-h: 37%, daytime: 47% and nighttime: 37%; COMB 24-h: 26%, daytime: 21% and nighttime: 32%; RES 24-h: 26%, daytime: 26% and nighttime: 35%; and ISO 24-h: 22%, daytime: 22% and nighttime: 39%. For diastolic BP, the prevalence of Responders was as follows: AE 24-h: 53%, daytime: 53% and nighttime: 31%; COMB 24-h: 26%, daytime: 26% and nighttime: 31%; RES 24-h: 35%, daytime: 22% and nighttime: 52%; and ISO 24-h: 44%, daytime: 33% and nighttime: 33%. Conclusion: There was a high inter-individual variation of BP after a single bout of various exercises in older adults. Responders had higher BP values on the control day without exercise. Various exercise modalities might acutely reduce 24-h BP in older adults with hypertension.

Individual differences in social interaction contexts: Examining the role of personality traits in the degree of self-other integration

There is increasing evidence in the joint action literature that the degree of self-other integration is sensitive to situational factors that affect the social interaction context. Until now, however, no study has addressed the potential role of dispositional factors such as personality traits in observed interindividual variations. The current study aims to address this gap. Using the joint Simon effect (JSE) as a measure of the degree of self-other integration, our results highlight that the magnitude of the JSE is consistently higher among participants with a high level of Extraversion and Agreeableness compared to those with a low level. This seems to indicate that extravert and agreeable people exhibit increased self-other integration, i.e., a greater propensity to integrate others' action representations. These results are the first experimental evidence that personality traits can mediate the degree of self-other integration in social interaction contexts. We discuss our findings, and suggest that considering individual differences would help to clarify inconsistent results reported in the joint action literature regarding the impact of certain situational factors on the degree of self-other integration.

Therapeutic and Metagenomic Potential of the Biomolecular Therapies against Periodontitis and the Oral Microbiome: Current Evidence and Future Perspectives.

The principles of periodontal therapy are based on the control of microbial pathogens and host factors that contribute to biofilm dysbiosis, with the aim of modulating the progression of periodontitis and periodontal tissue destruction. It is currently known how differently each individual responds to periodontal treatment, depending on both the bacterial subtypes that make up the dysbiotic biofilm and interindividual variations in the host inflammatory response. This has allowed the current variety of approaches for the management of periodontitis to be updated by defining the goals of target strategies, which consist of reducing the periodontopathogenic microbial flora and/or modulating the host-mediated response. Therefore, this review aims to update the current variety of approaches for the management of periodontitis based on recent target therapies. Recently, encouraging results have been obtained from several studies exploring the effects of some targeted therapies in the medium- and long-term. Among the most promising target therapies analyzed and explored in this review include: cell-based periodontal regeneration, mediators against bone resorption, emdogain (EMD), platelet-rich plasma, and growth factors. The reviewed evidence supports the hypothesis that the therapeutic combination of epigenetic modifications of periodontal tissues, interacting with the dysbiotic biofilm, is a key step in significantly reducing the development and progression of disease in periodontal patients and improving the therapeutic response of periodontal patients. However, although studies indicate promising results, these need to be further expanded and studied to truly realize the benefits that targeted therapies could bring in the treatment of periodontitis.

Heschl's gyrus duplication pattern and clinical characteristics in borderline personality disorder: A preliminary study.

Inter-individual variations in the sulco-gyral pattern of Heschl's gyrus (HG) might contribute to emotional processing. However, it remains largely unknown whether borderline personality disorder (BPD) patients exhibit an altered HG gyrification pattern, compared with healthy individuals, and whether such a brain morphological feature, if present, might contribute to their clinical characteristics. The present study used magnetic resonance imaging to investigate the distribution of HG gyrification patterns (single or duplicated) and their relationship to clinical characteristics in teenage BPD patients with minimal treatment exposure. No significant difference was noted for the prevalence of HG patterns between 20 BPD and 20 healthy participants. However, the BPD participants with left duplicated HG were characterized by higher prevalence of comorbid disruptive behavior disorders, with higher externalizing score compared with those with left single HG. Our preliminary results suggest that neurodevelopmental pathology associated with gyral formation might be implicated in the neurobiology of early BPD, especially for emotional and behavioral control.

A multi-population-based genomic analysis uncovers unique haplotype variants and crucial mutant genes in SARS-CoV-2

BackgroundCOVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rigorous detection and treatment strategies against SARS-CoV-2 have become very challenging due to continuous evolutions to the viral genome. Therefore, careful genomic analysis is sorely needed to understand transmission, the cellular mechanism of pathogenicity, and the development of vaccines or drugs. ObjectiveIn this study, we intended to identify SARS-CoV-2 genome variants that may help understand the cellular and molecular foundation of coronavirus infections required to develop effective intervention strategies. MethodsSARS-CoV-2 genome sequences were downloaded from an open-source public database, processed, and analyzed for variants in target detection sites and genes. ResultsWe have identified six unique variants, G---AAC, T---AAC---T, AAC---T, AAC--------T, C----------T, and C--------C, at the nucleocapsid region and eleven major hotspot mutant genes: nsp3, surface glycoprotein, nucleocapsid phosphoprotein, ORF8, nsp6, nsp2, nsp4, helicase, membrane glycoprotein, 3′-5′ exonuclease, and 2′-O-ribose methyltransferases. In addition, we have identified eleven major mutant genes that may have a crucial role in SARS-CoV-2 pathogenesis. ConclusionStudying haplotype variants and 11 major mutant genes to understand the mechanism of action of fatal pathogenicity and inter-individual variations in immune responses is inevitable for managing target patient groups with identified variants and developing effective anti-viral drugs and vaccines.

Trends of fecal calprotectin levels and associations with early life experience in preterm infants.

Preterm infants are at risk for severe infections due to their immature immune systems. Factors such as early life pain/stress experiences and feeding may influence immune activation and maturation of immune systems. However, the underlying mechanism remains unclear. Fecal calprotectin (FCP) is a noninvasive surrogate biomarker of mucosal inflammation in the gastrointestinal tract and has been used in detecting intestinal inflammation in specific pediatric gastrointestinal disorders. To describe the longitudinal trajectory of FCP levels in preterm infants and investigate the contributing factors that are associated with FCP levels. A longitudinal study design was used. Preterm infants were recruited from 2 neonatal intensive care units (NICU) of a children's medical center in the North-eastern US. Preterm infants were followed during their first 4 weeks of NICU hospitalization. Stool samples were collected twice per week to quantify the FCP levels. Cumulative pain/stress experiences and feeding types were measured daily. A linear mixed-effect model was used to examine the associations between FCP levels and demographic and clinical characteristics, cumulative pain/stress, and feeding over time. Forty-nine preterm infants were included in the study. Infants' FCP levels varied largely with a mean of 268.7±261.3µg/g and increased over time. Preterm infants experienced an average of 7.5±5.0 acute painful procedures and 15.3±20.8 hours of chronic painful procedures per day during their NICU stay. The mean percentage of mother's own milk increased from the first week (57.1±36.5%) to the fourth week (60.7±38.9%) after birth. Elevated FCP concentration was associated with acute and cumulative (chronic) pain/stress levels, mother's own milk, non-White race, and higher severity of illness score. FCP levels were elevated in preterm infants with wide interindividual and intraindividual variations. Cumulative pain/stress during the NICU hospitalization, feeding, race, and health status may influence FCP concentrations in early life that may be associated with inflammatory gut processes.

Nontargeted and Targeted Metabolomics Identifies Dietary Exposure Biomarkers for Navy Bean and Rice Bran Consumption in Children and Adults.

Dietary exposure biomarkers are needed for advancing knowledge on healthy foods. This study examined biomarkers for navy beans and rice bran in children and adults. Plasma, urine, stool, and study foods from dietary intervention studies were analyzed by metabolomics. A total of 38 children and 49 adults were assessed after consuming navy beans and/or rice bran for 2-, 4-, 6-, or 12 weeks. From the 138-175 metabolites modulated by diet, 11 were targeted for quantification. Trigonelline and pipecolate concentrations increased in children and adult plasma after 4 weeks compared to baseline. Increased xanthurenate (46%) was observed in children plasma after rice bran intake for 4 weeks. Study foods with navy beans had higher S-methylcysteine compared to control and supported the increased urine S-methylcysteine sulfoxide. Nontargeted metabolomics was moderately effective to identify target molecules as candidate biomarkers. Study limitations include interindividual metabolite variations before diet intervention. Validation is warranted using cross-over designs and larger sample sizes.

The COVID-19 Pandemic and Explaining Outcomes in Africa: Could Genomic Variation Add to the Debate?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, emanated from the Wuhan Province in China and rapidly spread across the globe causing extensive morbidity and mortality rate, and affecting the global economy and livelihoods. Contrary to early predictions of "body bags" across Africa, the African COVID-19 pandemic was marked by apparent low case numbers and an overall mortality rate when compared with the other geographical regions. Factors used to describe this unexpected pattern included a younger population, a swifter and more effective national health policy, limited testing capacities, and the possibility of inadequate reporting of the cases, among others. However, despite genomics contributing to interindividual variations in many diseases across the world, there are inadequate genomic and multiomics data on COVID-19 in Africa that prevent richer transdisciplinary discussions on the contribution of genomics to the spread of COVID-19 pandemic. To invite future debates on comparative studies of COVID-19 genomics and the pandemic spread around the world regions, this expert review evaluates the reported frequency distribution of genetic variants in candidate genes that are likely to affect COVID-19 infection dynamics/disease outcomes. We propose here that genomic variation should be considered among the many factors determining the COVID-19 infection and its outcomes in African populations and across the world.

Intra-abdominal and perineal pressures during abdominal exercises: A cross sectional study in postpartum women.

Low intra-abdominal pressure (IAP) and high perineal pressure (PP) are safe conditions for pelvic floor. This study aims to measure IAP and PP in Beninese post-partum women during abdominal exercises and determine what exercise presents less risk for pelvic floor after delivery. IAP and PP were measured at rest and during exercises performed in random order: Cough, pelvic floor contraction (PFC), Curl-up, diaphragmatic aspiration (DA), Drawing-in, DA + Curl-up and Drawing-in+Curl-up, using a Micro-Full biofeedback PHENIX-Vivaltis with dual-channel probe. Results were presented as change from rest (maximal value during exercise minus value at rest) and expressed in percentage of this change for the reference exercise, Cough for IAP and PFC for PP. The ANOVA repeated measures test was used to compare pressures between exercises. Seventeen postpartum women participated to this study. The maximal IAP and PP change were the highest (100%), respectively, during cough and PFC. During DA, IAP was the lowest (-7%) and PP was 51%. During Curl-up, IAP was moderate (43%) and significantly higher than during PFC (33%), Drawing-in (16%) and DA. PP was low (29%) and similar to that during Drawing-in (23%). Compared to Curl-up, Drawing-in+Curl-up increased PP (50%) but did not decrease IAP (40%). DA + Curl-up increased PP (58%) and decreased IAP (31%) compared to Curl-up but not compared to DA. DA is safe and Curl-up presents little risk for the pelvic floor. According to interindividual variations observed in IAP and PP, intrinsic factors should be considered in future studies.

Antibody and T-Cell Subsets Analysis Unveils an Immune Profile Heterogeneity Mediating Long-term Responses in Individuals Vaccinated Against SARS-CoV-2.

Based on the fact that coronavirus disease 2019 (COVID-19) is still spreading despite worldwide vaccine administration, there is an imperative need to understand the underlying mechanisms of vaccine-induced interindividual immune response variations. We compared humoral and cellular immune responses in 127 individuals vaccinated with either BNT162b2, mRNA-1273, or ChAdOx1-nCoV-19 vaccine. Both mRNA vaccines induced faster and stronger humoral responses as assessed by high spike- and RBD-specific antibody titers and neutralizing efficacy in comparison to ChAdOx1-nCoV-19 vaccine. At 7 months postvaccination, a decreasing trend in humoral responses was observed, irrespective of the vaccine administered. Correlation analysis between anti-S1 IgG and interferon- (IFN-) production unveiled a heterogeneous immune profile among BNT162b2-vaccinated individuals. Specifically, vaccination in the high-responder group induced sizable populations of polyfunctional memory CD4 helper T cells (TH1), follicular helper T cells (TFH), and T cells with features of stemness (TSCM), along with high neutralizing antibody production that persisted up to 7 months. In contrast, low responders were characterized by significantly lower antibody titers and memory T cells and a considerably lower capacity for interleukin-2 and IFN- production. We identified that long-term humoral responses correlate with the individuals ability to produce antigen-specific persistent memory T-cell populations.

Evaluation of 14-day Concentration-time Curves of Vitamin D3 and 25-Hydroxyvitamin D3 in Healthy Adults With Varying Body Mass Index.

To analyze the concentration-time curves of single-dose oral 25(OH)D3 in comparison with vitamin D3 in healthy adults. The pharmacokinetics observed over two weeks after orally administering single 900 μg doses of vitamin D3 and 25(OH)D3 to six otherwise healthy vitamin D insufficient/deficient adults participating in a broader randomized, double-blind, crossover, single center trial was analyzed. The study protocol was approved by the institutional review board (H-37167). Individual concentration-time curves revealed that vitamin D3 took longer than 25(OH)D3 to reach its maximal concentration after ingestion in five participants. After 25(OH)D3 ingestion, 25(OH)D3 reached its maximal concentration, dropped rapidly, and plateaued before starting to decrease slowly. There were observable inter-individual variations in the bioavailability of vitamin D3 and 25(OH)D3 and the pattern of changes in 25(OH)D3 concentration after their ingestion. Pharmacokinetics of 25(OH)D3 in comparison with vitamin D3 was illustrated and described in this study.

Laboratory Diagnosis and Classification of Von Willebrand Disease: A Review

Von Willebrand Disease (VWD), as the most common inherited bleeding disorder, is a widely misdiagnosed disease due to several diagnostic pitfalls. At the heart of this challenge lies the complexity and heterogeneity of VWF, significant (pre-) analytic issues, limited access to a comprehensive repertoire of laboratory assays, inter-individual variations, lack of expertise and complex interpretation of results. Next to a personal and family bleeding history, an array of clinical laboratory tests is required because no single test reflects both quantity and quality of VWF. The assays measure different VWF properties and may be affected by (pre-) analytic variables possibly leading to inaccurate interpretation. Therefore, a laboratory investigation and diagnosis according to a standard algorithm, and repetitive testing, are essential for accurate diagnosis which is illustrated in detail in this review.

Pharmacometabolomics-Based Translational Biomarkers: How to Navigate the Data Ocean.

Metabolome is the end point of the genome-environment interplay, and enables an important holistic overview of individual adaptability and host responses to environmental, ecological, as well as endogenous changes such as disease. Pharmacometabolomics is the application of metabolome knowledge to decipher the mechanisms of interindividual and intraindividual variations in drug efficacy and safety. Pharmacometabolomics also contributes to prediction of drug treatment outcomes on the basis of baseline (predose) and postdose metabotypes through mathematical modeling. Thus, pharmacometabolomics is a strong asset for a diverse community of stakeholders interested in theory and practice of evidence-based and precision/personalized medicine: academic researchers, public health scholars, health professionals, pharmaceutical, diagnostics, and biotechnology industries, among others. In this expert review, we discuss pharmacometabolomics in four contexts: (1) an interdisciplinary omics tool and field to map the mechanisms and scale of interindividual variability in drug effects, (2) discovery and development of translational biomarkers, (3) advance digital biomarkers, and (4) empower drug repurposing, a field that is increasingly proving useful in the current era of Covid-19. As the applications of pharmacometabolomics are growing rapidly in the current postgenome era, next-generation proteomics and metabolomics follow the example of next-generation sequencing analyses. Pharmacometabolomics can also empower data reliability and reproducibility through multiomics integration strategies, which use each data layer to correct, connect with, and inform each other. Finally, we underscore here that contextual data remain crucial for precision medicine and drug development that stand the test of time and clinical relevance.

Bone Turnover in Relation to Thyroid-Stimulating Hormone in Hypothyroid Patients on Thyroid Hormone Substitution Therapy.

Background Bone turnover markers (BTMs) have emerged as a useful tool for monitoring bone remodeling activity in the skeleton, and their serum levels correlate with bone loss rates in osteoporotic and normal individuals. Whether the same holds for other metabolic bone diseases is still subject to discussion. Methods We analyzed the relation between levels of BTMs and TSH in 79 females on thyroid hormone substitution therapy for hypothyroidism. Based on the reference range for TSH (0.2–4.0 mU/L) in our lab, we assessed BTMs in five different groups of patients based on the following criteria: (1) hypothyroidism (TSH >4.0); (2) TSH in the high normal range (1.0–4.0); (3) TSH in the low normal range (0.2–1.0); (4) TSH below the normal range (0.01–0.2); (5) TSH undetectable (<0.01). We studied the relationship between TSH and four different bone markers: procollagen type 1 N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin (OC), and bone specific alkaline phosphatase (BSAP). In a subgroup of patients, bone mineral density was assessed by a DXA scan. Results PINP emerged as the most sensitive and dynamic BTM for assessment of bone turnover in this patient group, achieving significant rho values on nonparametric correlation analysis for both TSH (rho −0.47; p=0.0001) and FT4 (rho 0.27; p=0.018). CTX and OC also revealed significant correlations to TSH, albeit with lower rho values (−0.37 and −0.24, respectively). Categorical analysis showed that bone turnover increased significantly, albeit with pronounced interindividual variability for TSH values below the lower limit of normal (0.2 mU/l), with the most severe affected being women exhibiting suppression of TSH. Further analysis of loss rates by DXA in a limited subgroup of patients showed that this was accompanied by accelerated bone loss. Conclusion PINP is the most sensitive marker of bone turnover in thyroid disorders. TSH values below the lower limit of normal are associated with increased bone turnover and accelerated bone loss, however, with pronounced interindividual variations. Assessment of PINP may be a valuable tool in cases where there is concern about possible adverse effects of thyroid hormone substitution therapy on bone.

Perceived Training of Junior Speed Skaters versus the Coach's Intention: Does a Mismatch Relate to Perceived Stress and Recovery?

The aim of this observational study was to examine the differences between training variables as intended by coaches and perceived by junior speed skaters and to explore how these relate to changes in stress and recovery. During a 4-week preparatory period, intended and perceived training intensity (RPE) and duration (min) were monitored for 2 coaches and their 23 speed skaters, respectively. The training load was calculated by multiplying RPE by duration. Changes in perceived stress and recovery were measured using RESTQ-sport questionnaires before and after 4 weeks. Results included 438 intended training sessions and 378 executed sessions of 14 speed skaters. A moderately higher intended (52:37 h) versus perceived duration (45:16 h) was found, as skaters performed fewer training sessions than anticipated (four sessions). Perceived training load was lower than intended for speed skating sessions (−532 ± 545 AU) and strength sessions (−1276 ± 530 AU) due to lower RPE scores for skating (−0.6 ± 0.7) or shorter and fewer training sessions for strength (−04:13 ± 02:06 hh:mm). All training and RESTQ-sport parameters showed large inter-individual variations. Differences between intended–perceived training variables showed large positive correlations with changes in RESTQ-sport, i.e., for the subscale’s success (r = 0.568), physical recovery (r = 0.575), self-regulation (r = 0.598), and personal accomplishment (r = 0.589). To conclude, speed skaters that approach or exceed the coach’s intended training variables demonstrated an increased perception of success, physical recovery, self-regulation, and personal accomplishment.

Autism Is Associated With Interindividual Variations of Gray and White Matter Morphology

BackgroundAlthough many studies have explored atypicalities in gray matter (GM) and white matter (WM) morphology of autism, most of them relied on unimodal analyses that did not benefit from the likelihood that different imaging modalities may reflect common neurobiology. We aimed to establish brain patterns of modalities that differentiate between individuals with and without autism and explore associations between these brain patterns and clinical measures in the autism group. MethodsWe studied 183 individuals with autism and 157 nonautistic individuals (age range, 6–30 years) in a large, deeply phenotyped autism dataset (EU-AIMS LEAP [European Autism Interventions—A Multicentre Study for Developing New Medications Longitudinal European Autism Project]). Linked independent component analysis was used to link all participants’ GM volume and WM diffusion tensor images, and group comparisons of modality shared variances were examined. Subsequently, we performed univariate and multivariate brain-behavior correlation analyses to separately explore the relationships between brain patterns and clinical profiles. ResultsOne multimodal pattern was significantly related to autism. This pattern was primarily associated with GM volume in bilateral insula and frontal, precentral and postcentral, cingulate, and caudate areas and co-occurred with altered WM features in the superior longitudinal fasciculus. The brain-behavior correlation analyses showed a significant multivariate association primarily between brain patterns that involved variation of WM and symptoms of restricted and repetitive behavior in the autism group. ConclusionsOur findings demonstrate the assets of integrated analyses of GM and WM alterations to study the brain mechanisms that underpin autism and show that the complex clinical autism phenotype can be interpreted by brain covariation patterns that are spread across the brain involving both cortical and subcortical areas.

Haematological changes from conception to childbirth: An indicator of major pregnancy complications.

About 800 women die every day worldwide from pregnancy-related complications, including excessive blood loss, infections and high-blood pressure (World Health Organization, 2019). To improve screening for high-risk pregnancies, we set out to identify patterns of maternal hematological changes associated with future pregnancy complications. Using mixed effects models, we established changes in 14 complete blood count (CBC) parameters for 1710 healthy pregnancies and compared them to measurements from 98 pregnancy-induced hypertension, 106 gestational diabetes and 339 postpartum hemorrhage cases. Results show interindividual variations, but good individual repeatability in CBC values during physiological pregnancies, allowing the identification of specific alterations in women with obstetric complications. For example, in women with uncomplicated pregnancies, haemoglobin count decreases of 0.12 g/L (95% CI -0.16, -0.09) significantly per gestation week (p value <.001). Interestingly, this decrease is three times more pronounced in women who will develop pregnancy-induced hypertension, with an additional decrease of 0.39 g/L (95% CI -0.51, -0.26). We also confirm that obstetric complications and white CBC predict the likelihood of giving birth earlier during pregnancy. We provide a comprehensive description of the associations between haematological changes through pregnancy and three major obstetric complications to support strategies for prevention, early-diagnosis and maternal care.

The influence of different dietary patterns on changes in the intestinal microbiota and human body weight

The human gut microbiome responds dynamically to changes in diet, contributing to the diversity of the human diet. The composition of the diet can also influence the metabolic products that are ultimately present in the intestinal lumen and plasma. Observations in humans on vegan, omnivorous, or synthetic enteral diets deficient in fiber have demonstrated dramatic imbalances in the gut microbiome, accompanied by changes in carbohydrate and amino acid-derived bacterial metabolites. It has been established that diet plays a dominant role in the formation of interindividual variations in host-associated microbial communities. Given the impact of the microbial community on human health and its multiple mechanisms of action, establishing the impact of different dietary approaches and models is critical.

SYMPHONY consortium: Orchestrating personalized treatment for patients with bleeding disorders

BackgroundTreatment choices for individual patients with an inborn bleeding disorder are increasingly challenging due to increasing options and rising costs for society. We have initiated an integrated interdisciplinary national research program. ObjectivesThe SYMPHONY consortium strives to orchestrate personalized treatment in patients with an inborn bleeding disorder, by unraveling the mechanisms behind interindividual variations of bleeding phenotype. PatientsThe SYMPHONY consortium will investigate patients with an inborn bleeding disorder, both diagnosed and not yet diagnosed. ResultsResearch questions are categorized under the themes: (1) diagnosis, (2) treatment, and (3) fundamental research, and consist of work packages addressing specific domains. Importantly, collaborations between patients and talented researchers from different areas of expertise promise to augment the impact of the SYMPHONY consortium, leading to unique interactions and intellectual property. ConclusionsSYMPHONY will perform research on all aspects of care, treatment individualization in patients with inborn bleeding disorders, as well as diagnostic innovations and results of molecular genetics and cellular model technology with regard to the hemostatic process. We believe that these research investments will lead to health‐care innovations with long‐term clinical and societal impact.This consortium has been made possible by a governmental, competitive grant from the Netherlands Organization for Scientific Research (NWO) within the framework of the NWA‐ORC Call grant agreement NWA.1160.18.038.