Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Behavioral Determinants and Consequences of Childhood Adiposity: Epidemiological studies in high-income populations

The aim of this thesis was to examine the relationship of parental- and child behaviors with the development of adiposity and cardiometabolic health in children, and to provide more insight in the direction of the associations by using data of prospective population-based studies in high-income populations. Most studies described in this thesis were embedded in The Generation R Study, a prospective population-based cohort study situated in Rotterdam, the Netherlands

Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: A longitudinal analysis of rapid progressors and long-term asymptomatics.

To gain more insight into the role of HIV-1-specific cytotoxic T lymphocytes (CTL) in the pathogenesis of AIDS, we investigated temporal relations between HIV-1 Gag-specific precursor CTL (CTLp), HIV-1 viral load, CD4+ T cell counts, and T cell function. Six HIV-1-infected subjects, who were asymptomatic for more than 8 yr with CD4+ counts > 500 cells/mm3, were compared with six subjects who progressed to AIDS within 5 yr after HIV-1 seroconversion. In the long-term asymptomatics, persistent HIV-1 Gag-specific CTL responses and very low numbers of HIV-1-infected CD4+ T cells coincided with normal and stable CD4+ counts and preserved CD3 mAb-induced T cell reactivity for more than 8 yr. In five out of six rapid progressors Gag-specific CTLp were also detected. However, early in infection the number of circulating HIV-1-infected CD4+ T cells increased despite strong and mounting Gag-specific CTL responses. During subsequent clinical progression to AIDS, loss of Gag-specific CTLp coincided with precipitating CD4+ counts and severe deterioration of T cell function. The possible relationships of HIV-1 Gag-specific CTLp to disease progression are discussed

Medically Unexplained Oropharyngeal Dysphagia at the University Hospital ENT Outpatient Clinic for Dysphagia: A Cross-Sectional Cohort Study

Medically unexplained oropharyngeal dysphagia (MUNOD) is a rare condition. It presents without demonstrable abnormalities in the anatomy of the upper aero-digestive tract and/or swallowing physiology. This study investigates whether MUNOD is related to affective or other psychiatric conditions. The study included patients with dysphagic complaints who had no detectible structural or physiological abnormalities upon swallowing examination. Patients with any underlying disease or disorder that could explain the oropharyngeal dysphagia were excluded. All patients underwent a standardized examination protocol, with FEES examination, the Hospital Anxiety and Depression Scale (HADS), and the Dysphagia Severity Scale (DSS). Two blinded judges scored five different FEES variables. None of the 14 patients included in this study showed any structural or physiological abnormalities during FEES examination. However, the majority did show abnormal piecemeal deglutition, which could be a symptom of MUNOD. Six patients (42.8%) had clinically relevant symptoms of anxiety and/or depression. The DSS scores did not differ significantly between patients with and without affective symptoms. Affective symptoms are common in patients with MUNOD, and their psychiatric conditions could possibly be related to their swallowing problems

A call for standardization:evaluating different methodologies to induce in vitro foreign body giant cell formation for biomaterials research and design

Foreign body giant cells (FBGCs) are crucial in the foreign body reaction at the biomaterial-tissue interface, forming through the fusion of cells from the monocyte/macrophage lineage and performing functions such as material degradation and fibrous encapsulation. Yet, their presence and role in biomaterials research is only slowly unveiled. This review analyzed existing FBGC literature identified through a search string and sources from FBGC articles to evaluate the most commonly used methods and highlight the challenges in establishing a standardized protocol. Our findings revealed a fragmented research landscape marked by significant variability in in vitro culture conditions, i.e., cell origin and type, culture media and sera, fusion-inducing factors, seeding density, culture surface, and inconsistencies in the read-outs. This complicates efforts toward standardization and hampers cross-study comparisons. Based on these results, we highlight the need and propose guidelines for standardized culture protocols for FBGC research. Overall, this review aims to underscore the relevance of improving reproducibility and reliability in FBGC research, facilitating effective cross-study comparisons and advancing understanding of FBGC formation and function, ultimately contributing to designing more effective biomaterial-based therapies. STATEMENT OF SIGNIFICANCE: Foreign body giant cells (FBGCs) are crucial in the body's response to implanted biomaterials. Yet, current research addressing their role and impact is highly fragmented. This review comprehensively and systematically examines the diverse methodologies and definitions used in FBGC research and identifies critical gaps and inconsistencies hindering the reproducibility and comparison of findings. By advocating for standardized protocols, we aim to enhance the reliability and equivalence of research, thus providing a stronger foundation for understanding biomaterial-driven FBGC formation and function. Establishing such a framework will impact biomaterial-based therapies, supporting their effectiveness and safety in medical applications, and is thus of relevance for scientists, companies, and clinicians in the biomaterial and medical device communities.</p

Potential of L-fucose isolated from Brown Seaweeds as Promising Natural Emulsifier compare to Carboxymethyl Cellulose (CMC)

L-fucose has been understood as sulfated polysaccharides and it could be extracted and fractionated from brown algae. These polysaccharides contains carbohydrate, sulfate, and protein that may be used as emulsifier. This research was aimed to study the emulsification properties of L-fucose through the determination of total dissolved solids (TDS), color CIE L*a*b* and stability of oil-in-water emulsion. As much as 0.5% of high concentrated L-fucose and 0.5% of carboxymethyl cellulose (CMC) were used as emulsifier in a 10% (v/v) oil-in-water (O/W) emulsion. The emulsifier was added to O/W emulsions and then heated at 72°C. Result of stability emulsion and TDS showed that L-fucose was comparable to the CMC but remarkable changed the color of O/W emulsion. Heating process significantly reduced the stability O/W emulsion when L-fucose was applied. As conclusion, L-fucose might be used as natural emulsifier in O/W emulsion but in the low heat treatment of food processing. This study may provide valuable information for utilizing natural emulsifier from abundant resources from nature

Heparin-guided binding of vascular endothelial growth factor to supramolecular biomaterial surfaces

Growth factors can steer the biological response to a biomaterial post implantation. Heparin is a growth factor binding molecule that can coordinate growth factor presentation to cells and therefore is able to regulate many biological processes. One way to functionalize biomaterials with heparin and growth factors is via a supramolecular approach. Here, we show a proof-of-concept study in which a supramolecular approach based on ureido-pyrimidinone (UPy) was used, which allows for modular functionalization. PCLdiUPy was functionalized with a UPy-modified heparin binding peptide (UPy-HBP) to facilitates binding of heparin, which in turn can bind vascular endothelial growth factor (VEGF) via its heparin binding domain. The adsorption of both heparin and VEGF were studied in two different functionalization approaches (pre-complex and two-step) and at different molecular ratios. Quartz crystal microbalance with dissipation energy adsorption data showed that VEGF and pre-complexed heparin:VEGF adsorbed non-specifically, with no distinguish between non-specific adsorption and heparin guided-adsorption. On the biological side, heparin guided-adsorption of Heparin:VEGF enhanced HUVECs surface coverage as compared to non-specific adsorption. These results provide a detailed insight on the molecular sandwich which is useful for new design strategies of supramolecular biomaterials with well-controlled immobilization of different growth factors.</p

Macrophage-driven biomaterial degradation depends on scaffold microarchitecture

In situ tissue engineering is a technology in which non-cellular biomaterial scaffolds are implanted in order to induce local regeneration of replaced or damaged tissues. Degradable synthetic electrospun scaffolds are a versatile and promising class of biomaterials for various in situ tissue engineering applications, such as cardiovascular replacements. Functional in situ tissue regeneration depends on the balance between endogenous neo-tissue formation and scaffold degradation. Both these processes are driven by macrophages. Upon invasion into a scaffold, macrophages secrete reactive oxygen species (ROS) and hydrolytic enzymes, contributing to oxidative and enzymatic biomaterial degradation, respectively. This study aims to elucidate the effect of scaffold microarchitecture, i.e., μm-range fiber diameter and fiber alignment, on early macrophage-driven scaffold degradation. Electrospun poly-ε-caprolactone-bisurea (PCL-BU) scaffolds with either 2 or 6 μm (Ø) isotropic or anisotropic fibers were seeded with THP-1 derived human macrophages and cultured in vitro for 4 or 8 days. Our results revealed that macroph age-induced oxidative degradation in particular was dependent on scaffold microarchitecture, with the highest level of ROS-induced lipid peroxidation, NADPH oxidase gene expression and degradation in the 6 μm Ø anisotropic group. Whereas, biochemically polarized macrophages demonstrated a phenotype-specific degradative potential, the observed differences in macrophage degradative potential instigated by the scaffold microarchitecture could not be attributed to either distinct M1 or M2 polarization. This suggests that the scaffold microarchitecture uniquely affects macrophage-driven degradation. These findings emphasize the importance of considering the scaffold microarchitecture in the design of scaffolds for in situ tissue engineering applications and the tailoring of degradation kinetics thereof. </p