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The recent rise in maternal workforce participation has led to more research regarding the role of maternal employment for (early) childhood mental health. This systematic review with meta-analysis covers new evidence on the association of both variables. A systematic literature search was conducted. Studies had to compare children 0–7 years of age on the basis of their mothers' employment status, working amount, employment duration, i.e., how long the mother had been back at work after birth, or timing of return to work. Child mental health was operationalized as behavior problems and prosocial behavior. Narrative and meta-analytic syntheses of evidence were conducted. Maternal employment was associated with more conduct problems but less internalizing behavior problems and anxious/depressed behavior in children; full-time employment was linked to more externalizing behavior problems and more hyperactivity/inattention. Longer employment duration was related to less (internalizing) behavior problems and more prosocial behavior but also more externalizing behavior problems. Narrative syntheses indicated early maternal return to work to be associated with more child externalizing behavior problems and less prosocial behavior. Whether maternal employment is associated with child mental health strongly depends on both variables' operationalization. Especially part-time employment, longer employment duration, and return to work only after the first year postpartum may be beneficial for child mental health. Practical implications pertain to an expanded offer of family leave and the endorsement of maternal employment after the first year postpartum. Here, factors that may buffer the negative associations with full-time employment warrant consideration. [ABSTRACT FROM AUTHOR]

Protein stability against aggregation is a major quality concern for the production of safe and effective biopharmaceuticals. Amongst the different drivers of protein aggregation, increasing evidence indicates that interactions between proteins and interfaces represent a major risk factor for the formation of protein aggregates in aqueous solutions. Potentially harmful surfaces relevant to biologics manufacturing and storage include air-water and silicone oil-water interfaces as well as materials from different processing units, storage containers, and delivery devices. The impact of some of these surfaces, for instance originating from impurities, can be difficult to predict and control. Moreover, aggregate formation may additionally be complicated by the simultaneous presence of interfacial, hydrodynamic and mechanical stresses, whose contributions may be difficult to deconvolute. As a consequence, it remains difficult to identify the key chemical and physical determinants and define appropriate analytical methods to monitor and predict protein instability at these interfaces. In this review, we first discuss the main mechanisms of surface-induced protein aggregation. We then review the types of contact materials identified as potentially harmful or detected as potential triggers of proteinaceous particle formation in formulations and discuss proposed mitigation strategies. Finally, we present current methods to probe surface-induced instabilities, which represent a starting point towards assays that can be implemented in early-stage screening and formulation development of biologics. [ABSTRACT FROM AUTHOR]

Ionotropic glutamate receptors include α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR), kainate receptors (KAR), and N-methyl-D-aspartate receptors (NMDAR). All function as cation channels; AMPAR and KAR are more permeable to sodium and NMDAR to calcium ions. Compared to the brain, receptor assemblies in platelets are unusual, suggesting distinctive functionalities. There is convincing evidence that AMPAR and KAR amplify platelet function and thrombus formation in vitro and in vivo. Transgenic mice lacking GluA1 and GluK2 (AMPAR and KAR subunits, respectively) have longer bleeding times and prolonged time to thrombosis in an arterial model. In humans, rs465566 KAR gene polymorphism associates with altered in vitro platelet responses suggesting enhanced aspirin effect. The NMDAR contribution to platelet function is less well defined. NMDA at low concentrations (≤10 μM) inhibits platelet aggregation and high concentrations (≥100 μM) have no effect. However, open NMDAR channel blockers interfere with platelet activation and aggregation induced by other agonists in vitro; anti-GluN1 antibodies interfere with thrombus formation under high shear rates ex vivo; and rats vaccinated with GluN1 develop iron deficiency anemia suggestive of mild chronic bleeding. In this review, we summarize data on glutamate receptors in platelets and propose a unifying model that reconciles some of the opposing effects observed. [ABSTRACT FROM AUTHOR]

Cells can form membraneless organelles by liquid–liquid phase separation. As these organelles are highly dynamic, it is crucial to understand the kinetics of these phase transitions. Here, we use droplet‐based microfluidics to mix reagents by chaotic advection and observe nucleation, growth, and coarsening in volumes comparable to cells (pL) and on timescales of seconds. We apply this platform to analyze the dynamics of synthetic organelles formed by the DEAD‐box ATPase Dhh1 and RNA, which are associated with the formation of processing bodies in yeast. We show that the timescale of phase separation decreases linearly as the volume of the compartment increases. Moreover, the synthetic organelles coarsen into one single droplet via gravity‐induced coalescence, which can be arrested by introducing a hydrogel matrix that mimics the cytoskeleton. This approach is an attractive platform to investigate the dynamics of compartmentalization in artificial cells. [ABSTRACT FROM AUTHOR]

Cells can form membraneless organelles by liquid–liquid phase separation. As these organelles are highly dynamic, it is crucial to understand the kinetics of these phase transitions. Here, we use droplet‐based microfluidics to mix reagents by chaotic advection and observe nucleation, growth, and coarsening in volumes comparable to cells (pL) and on timescales of seconds. We apply this platform to analyze the dynamics of synthetic organelles formed by the DEAD‐box ATPase Dhh1 and RNA, which are associated with the formation of processing bodies in yeast. We show that the timescale of phase separation decreases linearly as the volume of the compartment increases. Moreover, the synthetic organelles coarsen into one single droplet via gravity‐induced coalescence, which can be arrested by introducing a hydrogel matrix that mimics the cytoskeleton. This approach is an attractive platform to investigate the dynamics of compartmentalization in artificial cells. [ABSTRACT FROM AUTHOR]

The size distribution and the rheological properties of dispersions of biological colloids are relevant quality attributes for a variety of industrial applications, including pharmaceutical, food, and cosmetic products. For instance, the biophysical properties of monoclonal antibodies and therapeutic proteins, which represent an important class of drugs in the pharmaceutical market, are important for their safety and efficacy. In this work, we apply a microfluidic diffusion platform to analyze protein sizes and interactions in high-concentration antibody solutions directly in the liquid state with minimal perturbation of the sample. We show that this method provides size distributions in a size range scaling from a few angstroms to hundreds of nanometers. The detection sensitivity of the technique is independent of the particle size, and the method provides number-average distributions, enabling the simultaneous detection of both monomeric species and soluble aggregates. We further show that the same platform can be applied to measure viscosity-scaling effects in crowded environments by probing the Brownian motion of several tracers with different sizes. Such tracers experience a shift from the microviscosity to the macroviscosity of the sample at a critical probe size that is equal to the characteristic dimension of the main components of the dispersions. The technique simultaneously provides quantitative measurement of the microrheological properties and the macroviscosity of the sample, as well as information on the characteristic size of the components of the solution. Overall, these methods represent attractive tools in the context of the analysis of sizes and interactions of proteins in both diluted and high-concentration solutions during development, manufacturing, and formulation. [ABSTRACT FROM AUTHOR]

In the last decades, the pharmaceutical market has experienced an increase in the number of therapeutic proteins. The high activity and selectivity of these macromolecules is often achieved at the expense of complex structures, which exhibit several biophysical properties that must be carefully controlled and optimized for the successful development of these drugs as well as for guaranteeing their quality and safety. This need has motivated the application of a variety of biophysical techniques to analyze properties of therapeutic proteins and protein solutions including interactions, aggregation, solubility, viscosity, and thermal stability. After briefly summarizing currently available experimental approaches, we highlight the emerging possibilities offered by advances in microfluidic technology for the analysis of therapeutic proteins during manufacturing and formulation. [ABSTRACT FROM AUTHOR]

Objective To determine whether the overall hemostasis potential (OHP) and calibrated automated thrombogram (CAT) were significantly different between dogs with thrombosis and normal dogs. Animals Ten dogs with clinical evidence of thromboembolic disease had both OHP and CAT performed. Forty healthy control dogs had OHP performed, and 23 of these also had CAT performed. Measurements and Main Results Dogs with thrombosis had significantly higher OHP ( P = 0.003), overall coagulation potential ( P = 0.0001), and maximum optical density (Max OD, P < 0.0001) than normal dogs, and a significantly longer delay in the start of clot formation ( P = 0.01). Max OD was higher than established reference intervals in 80% of the dogs with thrombosis. Using the CAT assay, dogs with thrombosis had a significantly longer lag time than normal dogs ( P < 0.001). Plasma fibrinogen concentration correlated positively with overall coagulation potential, OHP, Max OD, and the slope of the OHP curve ( P < 0.05), and was increased in 90% of dogs with thrombosis. Conclusions The OHP assay findings were significantly different between normal dogs and those with thrombosis. CAT did not detect any significant differences between these populations of dogs, other than the lag time of the assay. [ABSTRACT FROM AUTHOR]

Hypercoagulability plays a key role in the progression of cardiovascular disease (CVD). Although omega-3 polyunsaturated fatty acid (PUFA) intake has been inversely related to the risk of cardiovascular events, themechanisms are not fully understood. The aim of this study was to investigate the effects of omega-3 on novel markers of global coagulation. The generation of fibrin and thrombin, measured via overall hemostasis potential (OHP) assay and calibrated automated thrombography, respectively, was determined in 40 healthy subjects and 16 patients with CVD at baseline and after 4 weeks of 640 mg/day omega-3 PUFA. In healthy subjects, fibrin generation was significantly reduced, as measured by overall coagulation potential (p = 0.013), OHP (p < 0.001), velocity of fibrin polymerization (p = 0.002), and significant increase in delay to fibrin generation (p = 0.002). The peak of generated thrombin was significantly reduced (p = 0.043). In subjects with CVD, omega-3 PUFA significantly reduced OHP and significantly increased the lag time to thrombin generation (both p < 0.001). Treatment with omega-3 PUFA had no effect on other fibrin and thrombin generation parameters in CVD patients. Four-week omega-3 PUFA supplementation reduced thrombotic potential in healthy subjects, as shown by reduced fibrin generation and peak thrombin. There was a greater effect on fibrin generation in healthy subjects compared with those with CVD. [ABSTRACT FROM AUTHOR]

Inherited macrothrombocytopenias are a clinically heterogeneous group of disorders, many of which cause moderate-to-severe bleeding tendencies in affected individuals, but which remain under-recognized and are frequently misdiagnosed as immune thrombocytopenia purpura. Diagnostic strategies to date have included a predominant phenotypic approach. The emergence of genetic testing and the implementation of next generation sequencing strategies in the investigation and diagnosis of these disorders have broadened our understanding of their pathogenesis, classification, and presentation. This review describes the increasingly expanding group of recognized inherited macrothrombocytopenias and highlights their pathophysiology and the role of phenotypic and genetic testing in their description and diagnosis. [ABSTRACT FROM AUTHOR]

Objective--To optimize the overall hemostasis potential (OHP) assay for use with canine platelet-poor plasma and determine reference intervals in healthy dogs. Animals--40 healthy dogs. Procedures--Blood was collected from the dogs into citrated tubes, and platlet-poor plasma was obtained. The OHP assay and standard coagulation assays (prothrombin time, activated partial thromboplastin time, and fibrinogen concentration) were performed for each sample. The OHP assay outputs were tested for correlations with results of the standard coagulation assays, age, and sex. Results--Modifications to the published methodology for the OHP assay were required for use with canine plasma, with less coagulation activator (thrombin) and more fibrino-lysis activator (tissue plasminogen activator) than used with human plasma. Male dogs had a higher OHP than did females. High fibrinogen concentrations were associated with increases in maximum optical density, OHP, and overall coagulation potential, and reduced prothrombin time was associated with increases in maximum optical density, overall coagulation potential, OHP, and maximum slope. Conclusions and Clinical Relevance--Results supported the use of the OHP assay as an accessible, cost-effective global coagulation assay. Further research is required to determine its clinical application as an alternative to thromboelastography or thrombin generation assays. [ABSTRACT FROM AUTHOR]

Hyperactivation and aggregation of platelets play a major role in thrombosis and hemostasis. The aims of this study were to investigate the effects of omega-3 polyunsaturated fatty acids (PUFAs) on platelet function. Light transmission aggregometry and flow cytometric analyses of platelet activation and platelet--leukocyte aggregates were determined at baseline and after 4 weeks of omega-3 (docosahexaenoic acid 520 mg and eicosapentaenoic acid 120 mg) supplementation. In total, 40 healthy subjects and 16 patients with a history of cardiovascular disease (CVD) completed the study. In healthy subjects, omega-3 PUFA significantly reduced adenosine diphosphate (ADP)--induced (maximum amplitude, 77.0% ± 3.2% vs. 71.6% ± 3.4%, p = 0.036; maximum slope, 86.3 ± 1.8 vs. 80.7 ± 2.1, p = 0.014) and adrenaline-induced platelet aggregation (maximum slope, 42.8 ± 2.7 vs. 37.4 ± 3.0, p = 0.013; lag time, 00:21 ± 00:02 vs. 00:31 ± 00:03 s, p = 0.002). Omega-3 PUFA also reduced P-selectin expression (40.5% ± 2.9% vs. 34.4% ± 2.4%, p = 0.049) on platelets and platelet-monocyte aggregates (38.5% ± 2.6% vs. 31.4% ± 2.5%, p = 0.022) after activation with ADP 0.5 µM. There were fewer changes in platelet aggregation and activation found in subjects with CVD. Nevertheless, there was a reduction in the slope of arachidonic acid--induced platelet aggregation (13.21 ± 6.41 vs. 4.88 ± 3.01, p = 0.009) and increased lag time for U46619 (00:16 ± 00:00 vs. 00:29 ± 00:07 s, p = 0.018) induced platelet aggregation. Thus, 4-week supplementation of 640 mg omega-3 PUFA reduced measures of platelet aggregation and activation in healthy subjects but effects were less evident in patients with existing CVD. Our findings support the recommendation that the omega-3 PUFA dose be higher in CVD than among healthy subjects. [ABSTRACT FROM AUTHOR]

Cell therapies have been used to regenerate the heart by direct myocardial delivery, by coronary infusion and by surface attached scaffolds. Multipotent mesenchymal stem cells (MSC) with capacity to differentiate into cardiomyocytes and other cell lines have been predominantly trialled in rodents. However, large animal models are increasingly needed to translate basic research into new, safe regenerative therapies. Understanding the mode of action of cell therapies in the mammalian heart has been limited by cell tracking capability. This study examined the ability to track the fate of allogeneic MSC in sheep using various fluorescent dyes. MSC isolated from sheep bone marrow were grown in culture following extraction and flow cytometric characterisation. After labelling with fluorescent tracking dyes (e.g. CFSE and DiI) cells were tested for in vitro and in vivo signal up to six weeks. Labelling effect on cell division and differentiation was studied. Several dyes lost fluorescence and slowed cell division. However, the thiol reactive dye CM-DiI showed detectable in vivo fluorescence in labelled MSC six weeks after injection into sheep skeletal muscle and two weeks after implantation of an MSC coated biomaterial scaffold. CM-DiI labelled MSC differentiated in vitro showed label retention over four weeks. The fluorescent membrane dye CM-DiI tracks implanted sheep MSC and provides an alternative to traditional cell markers such as gene modified GFP. [Copyright &y& Elsevier]

The use of mean platelet diameter (MPD) to classify inherited thrombocytopenia (IT) has been demonstrated in several studies. Alternatively, the mean platelet volume (MPV) may be used, but in macrothrombocytopenia this may not be available. We hypothesized that platelet forward scatter (FSC) measurements using flow cytometry may be used for the size-based classification of IT. The study aimed to assess the ability of platelet FSC to measure platelet size and whether it could be used as an alternative to the MPD or MPV. Blood samples were obtained from individuals undergoing investigation for inherited platelet function disorders (IPFD, n = 40) or platelet number disorders (IPND, n = 46). A hematology analyzer was used to obtain MPV and platelet counts, flow cytometry to measure platelet FSC and ImageJ software to measure MPD from stained blood smears. The International Society of Thrombosis and Hemostasis (ISTH) Bleeding Assessment Tool (BAT) was used to calculate bleeding scores. Twenty-nine(63%) of IPND patients had an MPV that could not be reported. A significant correlation to platelet FSC was found to the MPD (p <.0001) and MPV (p <.0001) and an inverse correlation with platelet count (p <.0001). No significant correlation was found between FSC and bleeding history. In conclusion, platelet FSC is an alternative to MPV and may be used in macrothrombocytopenia where the MPV is not recorded [ABSTRACT FROM AUTHOR]

An increasing body of evidence shows that membraneless organelles are key components in cellular organization. These observations open a variety of outstanding questions about the physico-chemical rules underlying their assembly, disassembly and functions. Some molecular determinants of biomolecular condensates are challenging to probe and understand in complex in vivo systems. Minimalistic in vitro reconstitution approaches can fill this gap, mimicking key biological features, while maintaining sufficient simplicity to enable the analysis of fundamental aspects of biomolecular condensates. In this context, microfluidic technologies are highly attractive tools for the analysis of biomolecular phase transitions. In addition to enabling high-throughput measurements on small sample volumes, microfluidic tools provide for exquisite control of self-assembly in both time and space, leading to accurate quantitative analysis of biomolecular phase transitions. Here, with a specific focus on droplet-based microfluidics, we describe the advantages of microfluidic technology for the analysis of several aspects of phase separation. These include phase diagrams, dynamics of assembly and disassembly, rheological and surface properties, exchange of materials with the surrounding environment and the coupling between compartmentalization and biochemical reactions. We illustrate these concepts with selected examples, ranging from simple solutions of individual proteins to more complex mixtures of proteins and RNA, which represent synthetic models of biological membraneless organelles. Finally, we discuss how this technology may impact the bottom-up fabrication of synthetic artificial cells and for the development of synthetic protein materials in biotechnology. • Experiments in test tubes can help us understanding fundamental aspects of biology • Microfluidic technology offers several advantages including: • high-throughput measurements on small sample volumes; • exquisite control of self-assembly in both time and space; • accurate quantitative analysis of several aspects of biomolecular phase transitions [ABSTRACT FROM AUTHOR]

Keywords: Kinetik; Membranlose Organellen; Mikrofluidik; Phasenübergänge; Prozesse außerhalb des Gleichgewichts Kinetik, Membranlose Organellen, Mikrofluidik, Phasenübergänge, Prozesse außerhalb des Gleichgewichts. [Extracted from the article]

Variants of the Diaphanous-Related Formin 1 (DIAPH-1) gene have recently been reported causing inherited macrothrombocytopenia. The essential/"diagnostic" characteristics associated with the disorder are emerging; however, robust and complete criteria are not established. Here, we report the first cases of DIAPH1-related disorder in Australia caused by the autosomal dominant gain-of-function DIAPH1 R1213X variant formed by truncation of the protein within the diaphanous auto-regulatory domain (DAD) with loss of regulatory motifs responsible for autoinhibitory interactions within the DIAPH1 protein. We affirm phenotypic changes induced by the DIAPH1 R1213X variant to include macrothrombocytopenia, early-onset progressive sensorineural hearing loss, and mild asymptomatic neutropenia. High-resolution microscopy confirms perturbations of cytoskeletal dynamics caused by the DIAPH1 variant and we extend the repertoire of changes generated by this variant to include alteration of procoagulant platelet formation and possible dental anomalies. [ABSTRACT FROM AUTHOR]

Background: Evidence on risk factors of birth-related posttraumatic stress disorder (PTSD) symptoms in mothers is increasing, whereas fathers are less examined. This study aims to determine differential predictors of PTSD symptoms in mothers and fathers.Methods: Data derive from the DREAM study, including 1,146 mothers and 828 fathers. We assessed mental health, work, and sociodemographic factors during pregnancy, pregnancy- and birth-related factors, and birth-related PTSD symptoms using the Impact of Event Scale-Revised 8 weeks postpartum. Structural equation models were estimated to examine associations between predictors and latent factors of PTSD symptoms for mothers and fathers simultaneously. Scaled chi-square difference tests were used to investigate differences between both groups in predictors.Results: Clinically relevant birth-related PTSD symptoms were found in 2.3% of mothers and 0.7% of fathers. Depressive and anxiety symptoms, pregnancy complications, and poorer subjective birth experience predicted PTSD symptoms in both groups. Additionally, lower support during birth and an unplanned cesarean section predicted PTSD symptoms in mothers, whereas lower job satisfaction, higher job burden, being first-time father, lower education, and mothers' lower support during birth were predictors for fathers. We found significant differences between groups regarding job burden during pregnancy, support during birth, and an unplanned cesarean section.Limitations: Generalization of findings might be limited by self-selection bias and some systematic dropout.Conclusions: Our results suggest differential predictors of PTSD symptoms in mothers and fathers. For fathers, less examined factors such as work factors may be important. Identifying differential risk factors may lead to customized prevention and treatment offers. [ABSTRACT FROM AUTHOR]

Background: Many mothers combine two sides of their life: They are both educated employees and family organizers. The aim of this study is to investigate risk and protective factors of depressive symptoms during the postpartum period (PPD symptoms) on both those sides of mothers' life, including education, job-, and housework-related factors.Methods: Data (n = 689) were drawn from the prospective-longitudinal cohort study "Dresden Study on Parenting, Work, and Mental Health" (DREAM). Education, job satisfaction, job burden, and the housework-related factor ministering to family needs (MTFN) were measured during pregnancy. Depressive symptoms were measured 8 weeks postpartum. Multiple linear regression analyses were conducted.Results: While education was not significantly associated with PPD symptoms, low job satisfaction, high job burden, and low MTFN levels were significant risk factors for PPD symptoms. When controlling for further potential confounders, job satisfaction and job burden remained significant predictors.Limitations: Generalization of findings might be limited due to participation bias and some systematic dropout.Conclusions: Job characteristics should be considered in future research on postpartum mental health. For the prevention of PPD symptoms, it seems important to ensure satisfying and less burdensome working conditions during pregnancy. Additionally, the results indicate that further research on the effects of housework-related factors on PPD symptoms is worthwhile. [ABSTRACT FROM AUTHOR]

The article describes the case of a patient diagnosed with delayed-onset heparin-induced thrombocytopenia (HIT) complicated by venous and arterial thromboses. It discusses the patient's medical history, characterization of HIT, results of the patient's medical tests, and treatment received by the patient.

GluN1 is a mandatory component ofN-methyl-D-aspartate receptors (NMDARs) best known for their roles in the brain, but with increasing evidence for relevance in peripheral tissues, including platelets. Certain anti-GluN1 antibodies reduce brain infarcts in rodent models of ischaemic stroke. There is also evidence that human anti-GluN1 autoantibodies reduce neuronal damage in stroke patients, but the underlying mechanism is unclear. This study investigated whether anti-GluN1-mediated neuroprotection involves inhibition of platelet function. Four commercial anti-GluN1 antibodies were screened for their abilities to inhibit human platelet aggregation. Haematological parameters were examined in rats vaccinated with GluN1. Platelet effects of a mouse monoclonal antibody targeting the glycine-binding region of GluN1 (GluN1-S2) were tested in assays of platelet activation, aggregation and thrombus formation. The epitope of anti-GluN1-S2 was mapped and the mechanism of antibody action modelled using crystal structures of GluN1. Our work found that rats vaccinated with GluN1 had a mildly prolonged bleeding time and carried antibodies targeting mostly GluN1-S2. The monoclonal anti-GluN1-S2 antibody (from BD Biosciences) inhibited activation and aggregation of human platelets in the presence of adrenaline, adenosine diphosphate, collagen, thrombin and a protease-activated receptor 1-activating peptide. When human blood was flowed over collagen-coated surfaces, anti-GluN1-S2 impaired thrombus growth and stability. The epitope of anti-GluN1-S2 was mapped to α-helix H located within the glycine-binding clamshell of GluN1, where the antibody binding was computationally predicted to impair opening of the NMDAR channel. Our results indicate that anti-GluN1-S2 inhibits function of human platelets, including dense granule release and thrombus growth. Findings add to the evidence that platelet NMDARs regulate thrombus formation and suggest a novel mechanism by which anti-GluN1 autoantibodies limit stroke-induced neuronal damage. [ABSTRACT FROM AUTHOR]

To date, research on the transition to parenthood and associated changes in relationship satisfaction (RS) has focused predominantly on mothers with their firstborn. This study targeted fathers to investigate their trajectories of RS with a particular focus on emerging differences between first- and second-time fathers. It furthermore considered various predictors such as the role of age, education, income, duration of relationship, marital status, child's biological sex, and child temperament. Data from a total of 606 fathers from the prospective longitudinal cohort study DREAM were analyzed. The analyses included assessments of four measurement time points (T1: prepartum; T2–T4: postpartum) over a period of more than 2 years. Latent growth curve modeling was applied with RS as the dependent variable and number of children as one of eight predictors of growth over time. First-time fathers showed higher initial RS, however experienced a steeper decline in the transition to parenthood than second-time fathers. At 8 weeks postpartum, first-time fathers still reported higher RS than second-time fathers. While RS continued to decline for first-time fathers up until 14 months postpartum, second-time fathers experienced an increase in RS. At 14 months and 2 years postpartum, second-time fathers showed higher RS scores than first-time fathers. Similar to first-time mothers, first-time fathers seem to experience a stronger RS decline during the transition to parenthood than second-time fathers, suggesting that especially couples becoming parents for the first time should be prepared for expected changes in their relationship. [ABSTRACT FROM AUTHOR]

Background: The association between mode of delivery (MOD) and parent-infant-bonding has only been studied in mothers and findings have been inconclusive. The aim of this study was to prospectively investigate how MOD relates to postpartum parent-infant-bonding in both mothers and fathers and whether these associations are mediated by birth experience. Methods: This study is part of the prospective cohort study "Dresden Study on Parenting, Work, and Mental Health" (DREAM). Our sample comprised N = 1,780 participants who completed quantitative questionnaires during pregnancy as well as 8 weeks and 14 months postpartum. MOD was dummy coded, contrasting spontaneous vaginal delivery against vaginal delivery induced by drugs, operative vaginal delivery, planned, and unplanned cesarean section. Parent-infant bonding and birth experience were assessed using validated scales. A moderated mediation analysis based on ordinary least square (OLS) regression and bootstrapped estimates was conducted, considering relevant confounding variables. Results: Compared to spontaneous vaginal delivery, all categories of MOD predicted more negative birth experiences in both parents. A more positive birth experience predicted stronger parent-infant-bonding at 8 weeks, but not at 14 months postpartum. Mothers who delivered via cesarean section (planned or unplanned) reported stronger parent-infant-bonding at 8 weeks and 14 months postpartum. In fathers, only unplanned cesarean section was associated with stronger parent-infant-bonding at 8 weeks postpartum. At 8 weeks postpartum, birth experience mediated the association between a vaginal delivery induced by drugs and a planned cesarean section and mother-infant-bonding and between a vaginal delivery induced by drugs, an operative vaginal delivery, and planned cesarean section and father-infant-bonding. At 14 months postpartum, birth experience mediated the association between a vaginal delivery induced by drugs, operative vaginal delivery, and planned cesarean section and parent-infant-bonding in both parents. Conclusions: The results emphasize the importance of the birth experience for parent-infant-bonding in both mothers and fathers. Further research should address the mechanisms by which parents with an unplanned cesarean section establish stronger parent-infant-bonding compared to parents whose baby was delivered via spontaneous vaginal delivery, despite their overall more negative birth experiences. [ABSTRACT FROM AUTHOR]

Abstract: Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin use. IgG antibodies to complexes of platelet factor 4 (PF4) and heparin trigger the clinical manifestations of HIT. Only a subset of these antibodies will activate platelets and these can only be identified with platelet aggregation (functional) assays. Heparin-induced platelet aggregation (HIPA) and 14C-serotonin release (SRA) assays for HIT are time-consuming and complex to perform. We have developed a whole blood impedance (WBI) test using the new Multiplate® analyser. All samples referred to our laboratory over a 10month period were screened for heparin-PF4 antibodies by an ELISA method (Zymutest HIA IgG). The 4T''s score was used to assess HIT pretest probability. Twenty antibody positive samples were further tested by all three functional assays: light transmission aggregometry (LTA), SRA and WBI. Thirteen out of twenty samples were positive by LTA (10 patients) and 15 by WBI (11 patients). SRA, considered to be the gold standard, was used as a confirmatory test and 11 were found to be positive (10 patients); four discrepant samples were weakly positive by WBI. The prevalence of a positive functional test was strongly correlated with the 4T''s clinical risk score, but a small number of low-risk patients had positive functional assays. In this study, the WBI assay detected all SRA positive patients and was positive for two others suggesting greater sensitivity. The rapid and easy to perform assay may be a useful tool for haematology laboratories to detect platelet-activating HIT antibodies. [Copyright &y& Elsevier]

Background: The COVID-19 pandemic has confronted working parents with an accumulation of stressors regarding changes in work, family, and social life, putting their mental health at risk. Stressors include altered working conditions such as working from home or changes in working hours as well as the difficulty to reconcile work and childcare due to the closure of childcare facilities. The present study examined the relationship of psychosocial work stress (i.e., work-privacy conflict and effort-reward imbalance at work) and depressive symptoms in working parents and whether this association was moderated by individual resilience. Methods: Data of the present study (n = 452) were collected in Germany between May and June 2020 as part of the DREAMCORONA study. A subsample of working mothers (n = 191) and fathers (n = 261) completed the subscale for work-privacy conflict (WPC) of the Copenhagen Psychosocial Questionnaire, the Effort-Reward Imbalance (ERI) Questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), and the Edinburgh Postnatal Depression Scale (EPDS). Multiple linear regression analyses including moderation were performed, controlling for gender, working hours per week, and a lifetime history of depression as potential confounders. Results: Both WPC (β = 0.336, p <.001) and ERI (β = 0.254, p <.001) were significantly associated with depressive symptoms. Resilience moderated the relationship between ERI and depressive symptoms (β = − 0.101, p =.018), indicating that higher resilience weakened the relationship. However, this effect was not found regarding the relationship between WPC and depressive symptoms (β = 0.055, p =.167). Conclusions: The results highlight the need for measures to reduce psychosocial work stressors such as WPC and ERI during the COVID-19 pandemic on the one hand and to promote resilience on the other hand. The findings partially support the potential protective role of resilience buffering the association between psychosocial stress and mental health in working parents. Longitudinal studies are needed to confirm this effect. [ABSTRACT FROM AUTHOR]

Introduction: Frailty is associated with changes in inflammation, coagulation, and possibly platelet function. Aspirin is still prescribed for stroke prevention in older patients with atrial fibrillation, although not recommended by current guidelines. In frail older people, it is unclear whether platelet aggregability and response to aspirin are altered. This study aims to investigate the effects of frailty and chronological age on platelet aggregability and on responses to aspirin in older patients with atrial fibrillation. Methods: Inpatients with atrial fibrillation aged ≥65 years were recruited from a tertiary referral hospital in Sydney, Australia. Frailty was determined using the Reported Edmonton Frail Scale. Platelet aggregation studies were performed using whole blood impedance aggregometry. Results: Data from 115 participants were analyzed (mean age 85 ± 6 years, 41% female, 52% frail). Spearman correlation coefficients found no significant associations of platelet aggregation with chronological age or with frailty score. Comparison between frail and non-frail groups showed that there was no impact of frailty status on aggregation assays amongst participants who were not taking any antiplatelet drugs. Amongst participants taking aspirin, the frail had higher adjusted arachidonic acid agonist (ASPI) test measures (AU per platelet) than the non-frail (0.11 ± 0.11 vs. 0.05 ± 0.04; p = 0.04), suggesting that in frail participants, platelet aggregation is less responsive to aspirin than in non-frail. Conclusions: We found no effect of chronological age or frailty status on platelet aggregation amongst older patients with atrial fibrillation in this pilot study. However, frailty could be associated with reduced aspirin responsiveness among older patients with atrial fibrillation. [ABSTRACT FROM AUTHOR]

Human megakaryocytes release glutamate and express glutamate-gated Ca 2 + -permeable N -methyl-D-aspartate receptors (NMDARs) that support megakaryocytic maturation. While deregulated glutamate pathways impact oncogenicity in some cancers, the role of glutamate and NMDARs in megakaryocytic malignancies remains unknown. The aim of this study was to determine if NMDARs participate in Ca 2 + responses in leukemic megakaryoblasts and if so, whether modulating NMDAR activity could influence cell growth. Three human cell lines, Meg-01, Set-2 and K-562 were used as models of leukemic megakaryoblasts. NMDAR components were examined in leukemic cells and human bone marrow, including in megakaryocytic disease. Well-established NMDAR modulators (agonists and antagonists) were employed to determine NMDAR effects on Ca 2 + flux, cell viability, proliferation and differentiation. Leukemic megakaryoblasts contained combinations of NMDAR subunits that differed from normal bone marrow and the brain. NMDAR agonists facilitated Ca 2 + entry into Meg-01 cells, amplified Ca 2 + responses to adenosine diphosphate (ADP) and promoted growth of Meg-01, Set-2 and K-562 cells. Low concentrations of NMDAR inhibitors (riluzole, memantine, MK-801 and AP5; 5–100 μM) were weakly cytotoxic but mainly reduced cell numbers by suppressing proliferation. The use-dependent NMDAR inhibitor, memantine (100 μM), reduced numbers and proliferation of Meg-01 cells to less than 20% of controls (IC 50 20 μM and 36 μM, respectively). In the presence of NMDAR inhibitors cells acquired morphologic and immunophenotypic features of megakaryocytic differentiation. In conclusion, NMDARs provide a novel pathway for Ca 2 + entry into leukemic megakaryoblasts that supports cell proliferation but not differentiation. NMDAR inhibitors counteract these effects, suggesting a novel opportunity to modulate growth of leukemic megakaryoblasts. [ABSTRACT FROM AUTHOR]

Background: Glutamate is stored in platelet dense granules and large amounts (>400μM) are released during thrombus formation. N-methyl-d-aspartate glutamate receptors (NMDARs) have been shown in platelets but their roles are unclear. Materials and methods: Platelet activation indices (CD62P expression and PAC-1 binding) and platelet aggregation were tested in the presence of well-characterized agonists (glutamate, NMDA, glycine) and antagonists (MK-801, memantine, AP5) of neuronal NMDARs. Expression of NMDAR subunits in platelets was determined. Results: NMDAR agonists facilitated and NMDAR antagonists inhibited platelet activation and aggregation. Low concentrations (100μM) of MK-801 and memantine reduced adrenaline-induced CD62P expression by 47±5 and 42±3%, respectively, and inhibited adrenaline-induced platelet aggregation by 17±6 and 25±5%, respectively (P <0.05). AP5 caused less inhibition of platelet function, requiring concentrations of at least 250μM to inhibit aggregation. NMDAR agonists did not aggregate platelets by themselves but enhanced aggregation initiated by low concentrations of ADP. Exogenous glutamate helped reverse inhibition of platelet aggregation by riluzole (inhibitor of glutamate release). Compared with seven possible NMDAR subunits in neurons, human platelets contained four: GluN1, GluN2A, GluN2D and GluN3A, a combination rarely seen in neurons. The presence of NMDAR transcripts in platelets implied platelet ability to regulate NMDAR expression presumably ‘on demand’. Flow cytometry and electron microscopy demonstrated that in non-activated platelets, NMDAR subunits were contained inside platelets but relocated onto platelet blebs, filopodia and microparticles after platelet activation. Conclusions: Our results support an active role for NMDARs in platelets, in a process that involves activation-dependent receptor relocation towards the platelet surface. [ABSTRACT FROM AUTHOR]

Abstract: Gene association with HLA suggests involvement of immune mediated mechanisms in the pathogenesis of Parkinson''s disease (PD). Only a small number of studies have found differences between circulating leukocyte populations in PD patients compared to controls, with conflicting results. To clarify whether there is a circulating leukocyte PD phenotype, we assessed the numbers of T, B and natural killer cells, and monocytes and found a small reduction (15–25%) in CD4+ T and CD19+ B cells in PD. These findings suggest some compromise in immune cells in PD and have potential implications for immune function and the progression of PD. [Copyright &y& Elsevier]

Introduction Obstructive sleep apnoea (OSA) is associated with increased cardiovascular risk, however the mechanisms are not well established. Objectives This study aimed to determine whether treatment of OSA with nasal continuous positive airway pressure (CPAP) would favourably alter coagulability across the sleepewake cycle. Methods In a randomised crossover trial, 28 patients received therapeutic or placebo CPAP, each for 2 months with a 1 month washout between treatments. After each treatment period, a 24 h coagulation study was conducted in the laboratory. Plasminogen activator inhibitor-1 (PAI-1), D-dimer, fibrinogen, von Willebrand Factor (vWF), factor VIII (FVIII), factor VII (FVII) and factor V (FV) were determined at seven time points over the day and night. Results At baseline, patients had severe OSA (Apnoea Hypopnoea Index 37.9623.9 events/h). Treatment of OSA with CPAP compared with placebo resulted in lower 24 h levels of vWF (-3.9%, p=0.013), FVIII (-6.2%, p=0.007) and FV (-4.2%, p<0.001). The greatest difference occurred during the nocturnal and early morning periods. In contrast, fibrinogen, D-dimer, FVII and PAI-1 did not differ between treatments, however all markers displayed diurnal variability independent of treatment. Conclusions In this randomised, placebo-controlled crossover trial, treatment of OSA with CPAP reduced the early morning level of vWF, and nocturnal levels of FVIII and FV. These findings suggest that CPAP may reduce cardiovascular risk in OSA, in part through reducing risk of thrombosis. INSET: Key messages. [ABSTRACT FROM AUTHOR]

Heparin-induced thrombocytopenia (HIT) is a rare but potentially serious complication of heparin use. Prompt diagnosis is crucial and requires the integration of clinical assessment and laboratory testing. Pretest clinical scoring systems (i.e., 4 Ts) have been established. Immunoassays can detect the presence of antibodies directed toward heparin-platelet factor 4 (H-PF4) complexes, but provide no information about their ability to activate platelets. A low clinical score, when combined with a negative immunoassay result obviates the need for further testing. However, immunoassays and 4 Ts scores have only modest specificity. Functional testing (serotonin release assay or heparin-induced platelet activation) remain important in confirming the presence of pathogenic H-PF4 antibodies, but are technically demanding to perform and limited in guiding clinical decisions in the acute setting. This review evaluates current immuno- and functional assays available in the laboratory diagnosis of HIT, and describes recent attempts to improve the specificity of enzyme immunoassays, including adopting an immunoglobulin G-specific assay and raising the optical density value cutoff for a positive result. The importance of donor selection and newer functional assays, including flow cytometry-based assays, are also discussed. A current approach to integrating clinical scoring, immunoassays, and functional testing for HIT is also outlined. [ABSTRACT FROM AUTHOR]

Taylor B, Tofler G, Morel-Kopp M-C, Carey H, Carter T, Elliott M, Dailey C, Villata L, Ward C, Woodward M, Schenck K. The effect of initial treatment of periodontitis on systemic markers of inflammation and cardiovascular risk: a randomized controlled trial. Eur J Oral Sci 2010; 118: 350–356. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Observational studies indicate that chronic periodontal disease is associated with adverse cardiovascular outcomes. The aim of this study was to determine whether initial periodontal treatment has a beneficial effect on systemic markers of inflammation and cardiovascular risk. One hundred and thirty-six adults with chronic periodontitis were allocated to either intervention or control groups in a 3-month randomized controlled intervention study. The intervention group received initial periodontal treatment, whereas the control group did not receive that treatment until after the study. Blood levels of cardiovascular risk factors, and of hematological, inflammatory, and metabolic markers, were measured at the beginning and the end of the study, and differences were calculated. Fibrinogen level was the primary outcome measure. Data for 61 persons in the intervention group and for 64 persons in the control group were available for statistical analysis. Compared with the control group, the intervention group showed a non-significant trend for a lower fibrinogen level. Significant increases in hemoglobin and hematocrit were seen after treatment, showing that initial periodontal treatment, a relatively simple and cost-effective intervention, has systemic effects. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented from doctors discussing mutation in GPIbΒ gene concomitant with severely reduced surface levels of CD9 protein.

Background: This study aims to examine whether physical activity (PA) before and during pregnancy and birth experience predict incident postpartum depressive (PPD) symptoms. Because PA may increase endurance and feelings of physical control, it may contribute to a positive birth experience and birth experience may mediate the association between PA before and during pregnancy and PPD symptoms.Methods: The study is part of the prospective-longitudinal cohort study "Dresden Study on Parenting, Work, and Mental Health" (DREAM). Participants were n = 1,254 (expectant) mothers. PA was assessed during pregnancy, birth experience and PPD symptoms 8 weeks postpartum. Multiple regression analyses were performed, including potential confounders.Results: A negative birth experience was linked to PPD symptoms, when controlling for relevant confounders. There was no evidence for a link between PA before and during pregnancy and birth experience or between PA during pregnancy and PPD symptoms. PA at low and at vigorous intensity before pregnancy was associated with PPD symptoms, but not when controlling for confounders. Because PA was not associated with birth experience, no mediation analysis was performed.Limitations: The current sample was relatively homogenous (i.e., mostly German native speakers, primiparous, highly educated). Birth experience was assessed retrospectively at 8 weeks following birth.Conclusions: Our results highlight the importance of the birth experience in the development of PPD symptoms. Promoting a positive birth experience represents a promising approach to prevent PPD symptoms. Further research on the association between PA and PPD symptoms is warranted. [ABSTRACT FROM AUTHOR]

Background: Platinum-based chemotherapy agents have been associated with potentially fatal acute immune-mediated hemolytic anemia. The target antigen, cause of the positive direct antiglobulin test (DAT) and mechanism of hemolysis have been the subject of controversy.Case Report: We report a patient who developed a DAT-positive hemolytic episode after a red cell (RBC) transfusion was delivered during the infusion of her 17th cycle of oxaliplatin. Standard pretransfusion testing was uncomplicated; however, after infusion, the serum was no longer compatible with the transfused units and a strong (4+) panreactive IgG antibody was detected.Results: The patient's serum from 10 days after the episode, only when therapeutic concentrations of oxaliplatin were added, reacted with all RBCs tested using the indirect antiglobulin test (IAT) (3+). The effect was retained with a purified IgG fraction and almost eliminated with IgG-depleted serum. Immunoprecipitation analysis revealed a band with the molecular weight of the Band 3 anion channel only in the presence of the patient's serum and oxaliplatin.Conclusion: Our investigations indicated that oxaliplatin interacted with both an IgG antibody and a RBC membrane epitope probably located on the Band 3 anion channel. [ABSTRACT FROM AUTHOR]

Background: The majority of Western women work during their reproductive years, but past research has often neglected the influence of work-related factors on postpartum mental health. Especially postpartum depression (PPD) is an enormous psychological burden for mothers. Therefore, this study aims to investigate the prospective impact of precarious working conditions and psychosocial work stress during pregnancy (such as work-privacy conflict and effort-reward imbalance at the job) on symptoms of maternal PPD.Methods: In the prospective-longitudinal cohort study DREAM (DResdner Studie zu Elternschaft, Arbeit und Mentaler Gesundheit), N = 587 employed women were questioned about their work during pregnancy and their mental health 8 weeks after delivery.Results: Multiple regression analyses revealed that work-privacy conflict, low reward at work, and precarious working conditions significantly predicted symptoms of PPD, even when controlling for lifetime depression, anxiety, education, parity, and age.Conclusion: Our results indicate that psychosocial work stress and precarious working conditions have important implications for maternal peripartum mental health. They might act as prospective risk factors for PPD during the period of maternal leave. Hence, future research should focus on preventative measures targeting work life. [ABSTRACT FROM AUTHOR]

• Higher work-privacy-conflict was associated with poorer parent–child-bonding. • When stratifying by parents' sex this association stayed significant only for men. • Working from home had no significant moderating effect on this association. During the COVID-19 pandemic, working parents have been faced with a double burden by struggling to satisfy their children's needs as well as dealing with altered working requirements at the same time. In the unprecedented context of a pandemic, the present study extends the existing literature to investigate the association between work-privacy-conflict (WPC) and parent–child-bonding in families with children aged 0–34 months old. Additionally, the potential moderating role of working from home is considered. Data of the present cross-sectional study (n = 385) were collected in Germany between May and June 2020 as part of the [name of the study will be inserted after the masked review]. Mothers (n = 165) and fathers (n = 220) currently working completed the Work-Privacy-Conflict Scale and the Postpartum Bonding Questionnaire. A hierarchical linear regression analysis including the confounders sex, working from home, working hours per week, age of index child, and childcare revealed a significant association between higher WPC and poorer parent–child-bonding (ß = 0.154, 95 % CI [0.02, 0.28]). In a second linear regression analysis stratified by sex, only the association within the sample of men remained significant (ß = 0.240, 95 % CI [0.07, 0.39]). Working from home had no significant moderating effect on the association between WPC and parent–child-bonding. Given our results, it seems particularly important for working parents to maintain a balance between work and private life as it could not only affect themselves but also the emotional connection to their child. Future research should consider additional factors, such as mental health, parenting, and couple dynamics when investigating the interference of WPC with parent–child-bonding. Additionally, a longitudinal approach will be necessary to establish causal relations between WPC and parent–child-bonding. [ABSTRACT FROM AUTHOR]

MYH9-related disorders (MYH9-RDs) caused by mutation of the MYH9 gene which encodes non-muscle myosin heavy-chain-IIA (NMMHC-IIA), an important motor protein in hemopoietic cells, are the most commonly encountered cause of inherited macrothrombocytopenia. Despite distinguishing features including an autosomal dominant mode of inheritance, giant platelets on the peripheral blood film accompanied by leucocytes with cytoplasmic inclusion bodies (döhle-like bodies), these disorders remain generally under-recognized and often misdiagnosed as immune thrombocytopenia (ITP). This may result in inappropriate treatment with corticosteroids, immunosupressants and in some cases, splenectomy. We explored the efficacy of next generation sequencing (NGS) with a candidate gene panel to establish the aetiology of thrombocytopenia for individuals who had been referred to our center from hematologists in the Australasian region in whom the cause of thrombocytopenia was suspected to be secondary to an inherited condition but which remained uncharacterized despite phenotypic investigations. Pathogenic MYH9 variants were detected in 15 (15/121, 12.4%) individuals and the pathogenecity of a novel variant of uncertain significance was confirmed in a further two related individuals following immunofluorescence (IF) staining performed in our laboratory. Concerningly, only one (1/17) individual diagnosed with MYH9-RD had been referred with this as a presumptive diagnosis, in all other cases (16/17, 94.1%), a diagnosis was not suspected by referring clinicians, indicating a lack of awareness or a failing of our diagnostic approach to these conditions. We examined the mean platelet diameter (MPD) measurements as a means to better identify and quantify platelet size. MPDs in cases with MYH9-RDs were significantly larger than controls (p < 0.001) and in 91% were greater than a previously suggested threshold for platelets in cases of ITP. In addition, we undertook IF staining in a proportion of cases and confirm that this test and/or NGS are satisfactory diagnostic tests. We propose that fewer cases of MYH9-RDs would be missed if diagnostic algorithms prioritized IF and/or NGS in cases of thrombocytopenia associated with giant platelets, even if döhle-like bodies are not appreciated on the peripheral blood film. Finally, our report describes the long-term use of a thrombopoietin agonist in a case of MYH9-RD that had previously been diagnosed as ITP, and demonstrates that treatment with these agents may be possible, and is well tolerated, in this group of patients. [ABSTRACT FROM AUTHOR]

Cells form stress granules (SGs) upon stress stimuli to protect sensitive proteins and RNA from degradation. In the yeast Saccharomyces cerevisiae, specific stresses such as nutrient starvation and heat-shock trigger recruitment of the yeast pyruvate kinase Cdc19 into SGs. This RNA-binding protein was shown to form amyloid-like aggregates that are physiologically reversible and essential for cell cycle restart after stress. Cellular Cdc19 exists in an equilibrium between a homotetramer and monomer state. Here, we show that Cdc19 aggregation in vitro is governed by protein quaternary structure, and we investigate the physical--chemical basis of Cdc19's assembly properties. Equilibrium shift toward the monomer state exposes a hydrophobic low-complexity region (LCR), which is prone to induce intermolecular interactions with surrounding proteins. We further demonstrate that hydrophobic/hydrophilic interfaces can trigger Cdc19 aggregation in vitro. Moreover, we performed in vitro biophysical analyses to compare Cdc19 aggregates with fibrils produced by two known dysfunctional amyloidogenic peptides. We show that the Cdc19 aggregates share several structural features with pathological amyloids formed by human insulin and the Alzheimer's disease--associated Aβ42 peptide, particularly secondary β-sheet structure, thermodynamic stability, and staining by the thioflavin T dye. However, Cdc19 aggregates could not seed aggregation. These results indicate that Cdc19 adopts an amyloid-like structure in vitro that is regulated by the exposure of a hydrophobic LCR in its monomeric form. Together, our results highlight striking structural similarities between functional and dysfunctional amyloids and reveal the crucial role of hydrophobic/hydrophilic interfaces in regulating Cdc19 aggregation. [ABSTRACT FROM AUTHOR]

Background: Parental work stress and impaired mental health seem to have intensified during the current COVID-19 pandemic. Both can have a negative impact on parent-child bonding: psychosocial work stress in the course of a spillover effect from work to family and symptoms of impaired mental health as part of a crossover effect from parent to child. This potentially affects the child’s development in the long term. Method: This cross-sectional study examined the relationship between psychosocial work stress and parent-child bonding during the early COVID-19 pandemic (May–June 2020). Symptoms of depression and aggressiveness were considered as mediators of this relationship. The sample consisted of employees in Eastern Germany (n = 380; 42.9% mothers, 57.1% fathers), aged 24–55 years, with children aged 0–36 months. Results: In the total sample, an association was only found after adjusting for potential confounders, indicating that higher psychosocial work stress is associated with weaker bonding between the parent and child (β = 0.148, p =.017, 95% CI [0.566, 5.614]). The separate analyses for mothers and fathers did not reveal a statistically significant relationship between psychosocial work stress and parent-child bonding. In the total sample, the higher the psychosocial work stress was, the higher were the parental symptoms of depression (β = 0.372, p <.001, 95% CI [3.417, 5.696]) and aggressiveness β = 0.254, p <.001, 95% CI [1.008, 3.208]). The mental health symptoms in turn were related to weaker parent-child bonding (symptoms of depression β = 0.320, p <.001, 95% CI [0.345, 0.749]; symptoms of aggressiveness β = 0.394, p <.001, 95% CI [0.697, 1.287]). The results furthermore suggested that parental mental health symptoms mediate the association between psychosocial work stress and parent-child bonding (symptoms of depression, ab = 2.491, 95% CI [1.472, 3.577] and of aggressiveness, ab = 2.091, 95% CI [1.147, 3.279]). The mediation effect was also found in the separate analyses for the mothers and fathers. Discussion: The results of this study during the early COVID-19 pandemic in Germany highlight the importance of prevention as well as intervention measures in relation to psychosocial work stress that may play a debilitating role in the context of family relationships. In addition, the results suggest that both employers and employees should be made aware of the importance of psychosocial work stress, as it can have a negative impact on mental health, which in turn may have a major influence on family relationships. [ABSTRACT FROM AUTHOR]

Cell culture process monitoring in monoclonal antibody (mAb) production is essential for efficient process development and process optimization. Currently employed online, at line and offline methods for monitoring productivity as well as process reproducibility have their individual strengths and limitations. Here, we describe a matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based on a microarray for mass spectrometry (MAMS) technology to rapidly monitor a broad panel of analytes, including metabolites and proteins directly from the unpurified cell supernatant or from host cell culture lysates. The antibody titer is determined from the intact antibody mass spectra signal intensity relative to an internal protein standard spiked into the supernatant. The method allows a semi-quantitative determination of light and heavy chains. Intracellular mass profiles for metabolites and proteins can be used to track cellular growth and cell productivity. [ABSTRACT FROM AUTHOR]

Hemizygous deletion of a variable region on chromosome 11q containing FLI1 causes an inherited platelet-related bleeding disorder in Paris-Trousseau thrombocytopenia and Jacobsen syndrome. These multisystem disorders are also characterized by heart anomalies, changes in facial structure, and intellectual disability. We have identified a consanguineous family with autosomal recessive inheritance of a bleeding disorder that mimics Paris-Trousseau thrombocytopenia but has no other features of the 11q23 deletion syndrome. Affected individuals in this family have moderate thrombocytopenia; absent collagen-induced platelet aggregation; and large, fused a-granules in 1% to 5% of circulating platelets. This phenotype was caused by a FLI1 homozygous c.970C>T-point mutation that predicts an arginine-to-tryptophan substitution in the conserved ETS DNA-binding domain of FLI1. This mutation caused a transcription defect at the promoter of known FLI1 target genes GP6, GP9, and ITGA2B, as measured by luciferase assay in HEK293 cells, and decreased the expression of these target proteins in affected members of the family as measured by Western blotting of platelet lysates. This kindred suggests abnormalities in FLI1 as causative of Paris-Trousseau thrombocytopenia and confirms the important role of FLI1 in normal platelet development. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Patients with stable coronary artery disease (CAD) are at risk of arterial thrombosis causing myocardial infarction. Detection of global haemostatic markers of hypercoagulability and hypofibrinolysis may be important for risk stratification and individualised treatment. We examined overall haemostatic potential (OHP) and thrombin generation in a group of stable CAD patients. We also sought to investigate associations between fibrinolytic inhibitors and abnormal global fibrinolysis in these patients. Materials and Methods: Blood samples were collected from 56 patients defined by coronary anatomy as symptomatically stable CAD. Medications were recorded. Samples were analysed using the global coagulation assays OHP and thrombin generation (calibrated automated thrombogram, CAT), platelet aggregometry measured by Multiplate®, and levels of plasminogen activator inhibitor-1 (PAI-1) antigen measured by ELISA. Results were compared with a reference group of healthy controls. Results: Stable CAD patients displayed increased fibrin and thrombin generation and impaired fibrinolysis (decreased overall fibrinolytic potential, OFP, and increased clot lysis time) compared with healthy controls. No effect of antiplatelet agents or other medications on these parameters was observed using platelet-poor plasma. After multivariate adjustment, OFP of healthy individuals was significantly associated with fibrinogen, but in CAD patients PAI-1 became an important determinant. Conclusions: Hypercoagulability of plasma is observed in stable CAD, with both increased thrombin generation and reduced fibrinolytic potential making a significant contribution. The OHP assay may provide a simple method of identifying hypercoagulability in individual patients. [Copyright &y& Elsevier]

Early bereavement is associated with increased cardiovascular events. The mechanism, however, has not been well studied. We assessed whether bereavement is associated with an increased heart rate (HR) and decreased heart rate variability that might contribute to increased cardiovascular risk. A total of 78 bereaved spouses and parents (55 women and 23 men; aged 34 to 87 years, mean 65) were studied with 24-hour Holter monitoring within 2 weeks of bereavement (acute) and at 6 months. Their findings were compared to those from a nonbereaved reference group (52 women and 27 men) aged 33 to 91 years (mean 63.6). All participants were in sinus rhythm. We assessed the mean HR, atrial and ventricular arrhythmias, and both time and frequency domain heart rate variability measures. Acute bereavement was associated with increased 24-hour HR (mean ± SE, 75.1 ± 1.1 vs 70.7 ± 1.0; p = 0.004) and reduced heart rate variability, as indicated by lower standard deviation of the NN intervals index (median 45.4 vs 49.9, p = 0.017), total power (7.78 ± 0.10 vs 8.02 ± 0.09, p = 0.03), very low frequency (7.23 ± 0.09 vs 7.44, p = 0.046) and low frequency (5.76 ± 0.12 vs 6.16 ± 0.09, p = 0.01). At 6 months, the bereaved had a significantly lower HR (p = 0.001) and increased standard deviation of the NN intervals index (p = 0.02), square root of the mean square of differences of successive intervals (p = 0.045), number of interval differences of successive NN intervals >50 ms divided by the number of NN intervals (p = 0.039), low-frequency power (p = 0.02), and high frequency (p = 0.002) compared to the initial acute levels. In conclusion, the present study, the first to report 24-hour HR monitoring in the early weeks of bereavement, has demonstrated increased HR and altered autonomic function that might contribute to the increased cardiovascular events in early bereavement. [ABSTRACT FROM AUTHOR]

Background: Bereavement is associated with increased cardiovascular risk, particularly in surviving spouses and parents, however the mechanism is not well understood due to limited studies. The purpose of this study was to evaluate haemodynamic changes (blood pressure (BP) and heart rate (HR)), that may contribute to increased cardiac risk in early bereavement. Methods: We enrolled 80 bereaved individuals and 80 non-bereaved as a reference group. Twenty-four hour ambulatory blood pressure monitoring was performed within two weeks (acute assessment) and at six months following bereavement. Results: Compared to the non-bereaved, the acutely bereaved had higher 24-hour systolic BP (mean (SE) 130.3 (1.5) vs 127.5 (1.4)mmHg, p =0.03), higher daytime systolic BP (135.6 (1.5) vs 131.6 (1.4)mmHg, p =0.02) and higher daytime systolic load (median % 39.0 vs 29.3, p =0.02). By six months the BP of the bereaved tended to be lower than acute measures. This difference was significant amongst those not taking BP lowering medications for 24-hour systolic BP (126.5 (2.4) vs 129.7 (2.3)mmHg, p =0.04), daytime systolic BP (129.8 (2.1) vs 133.9 (2.0)mmHg, p =0.01) and daytime diastolic pressure (76.7 (1.0) vs 78.9 (0.9)mmHg, p =0.03). Twenty-four hour heart rate was also higher acutely in the bereaved compared with the reference group (74.0 (1.2) vs 71.7 (0.9) b/min, p =0.02); at six months heart rate in the bereaved had fallen to non-bereaved levels (70.4 (0.09), p =0.02). Conclusion: Early bereavement is associated with increased systolic blood pressure and heart rate. These haemodynamic changes may contribute to a time-limited increase in cardiovascular risk. [ABSTRACT FROM AUTHOR]

Ischaemic brain damage induces autoimmune responses, including the production of autoantibodies with potential neuroprotective effects. Platelets share unexplained similarities with neurons, and the formation of anti-platelet antibodies has been documented in neurological disorders. The aim of this study was to investigate the presence of anti-platelet antibodies in the peripheral blood of patients after ischaemic stroke and determine any clinical correlations. Using a flow cytometry-based platelet immunofluorescence method, we detected platelet-reactive antibodies in 15 of 48 (31%) stroke patients and two of 50 (4%) controls (p < 0.001). Western blotting revealed heterogeneous reactivities with platelet proteins, some of which overlapped with brain proteins. Stroke patients who carried anti-platelet antibodies presented with larger infarcts and more severe neurological dysfunction, which manifested as higher scores on the National Institutes of Health Stroke Scale (NIHSS; p = 0.009), but they had a greater recovery in the NIHSS by the time of hospital discharge (day 7 ± 2) compared with antibody-negative patients (p = 0.043). Antibodies from stroke sera reacted more strongly with activated platelets (p = 0.031) and inhibited platelet aggregation by up to 30.1 ± 2.8% (p < 0.001), suggesting the potential to interfere with thrombus formation. In conclusion, platelet-reactive antibodies can be found in patients soon after ischaemic stroke and correlate with better short-term outcomes, suggesting a potential novel mechanism limiting thrombosis. [ABSTRACT FROM AUTHOR]