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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]

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]

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]

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]

Background: The first 2 years of life are a particularly sensitive period for the parent-child relationship as well as a healthy, age-appropriate child development. Both have been shown to be linked to postpartum depressive and anxiety symptoms, while the role of obsessive-compulsive symptoms, which are also common, is still largely understudied. In addition, fathers have been neglected in this area of research. This study, which includes both mothers and fathers, aims to investigate the longitudinal associations between postpartum obsessive-compulsive symptoms and different domains of child development, as well as the mediating role of the parent-child relationship. Methods: Data were drawn from the prospective longitudinal study DREAM, with 674 mothers and 442 fathers from the general population completing self-report questionnaires at four measurement points. Longitudinal associations between parental postpartum obsessive-compulsive symptoms 8 weeks postpartum, the parent-child relationship 14 months postpartum, and child development 24 months postpartum were investigated using regression and mediation analyses. A number of potential confounding variables were considered, i.e., age, academic degree, postpartum depressive and anxiety symptoms of the parents, preterm birth and temperament of the child, as well as COVID-19 pandemic-driven adversities. Results: When adjusting for confounders, neither maternal nor paternal postpartum obsessive-compulsive symptoms had adverse effects on the respective parent-child relationship and child development. Further, no mediating role of the parent-child relationship between parental postpartum obsessive-compulsive symptoms and child development could be confirmed. Instead, we found that the mother- and father-child relationship were differentially related to specific child developmental domains. For mothers, a poorer mother-child relationship was prospectively related to poorer fine motor development. For fathers, a poorer father-child relationship prospectively predicted a poorer overall development as well as poorer gross motor, fine motor, problem-solving, and personal-social development. Conclusion: Our results suggest that negative effects on the parent-child relationship and child development may only become apparent in full-blown postpartum obsessive-compulsive disorder. Given the differential impact on specific developmental domains, our findings also suggest that it is crucial to consider both parents in clinical practice as well as in future research, rather than focusing only on the mother-child dyad. [ABSTRACT FROM AUTHOR]

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]

Objective: To explore the longitudinal associations between prepartum fear of childbirth (FOC), birth experience, and postpartum mother-child-bonding, and the potential mediator role of the birth experience. Design: Women from the prospective cohort study DREAM completed questionnaires during pregnancy, 8 weeks, and 14 months after the birth. Participants: A community sample of n = 645 pregnant women from a large city in Eastern Germany participated in the study. Results: In a regression analysis, FOC predicted negative birth experience (β = 0.208, p < 0.001) which in turn predicted poorer mother-child-bonding both at 8 weeks (β = 0.312, p < 0.001) and 14 months postpartum (β = 0.200, p < 0.001). FOC also predicted mother-child-bonding at 14 months postpartum (β = 0.098, p < 0.05). Of note, this association was mediated by birth experience both at 8 weeks, indirect effect ab = 0.065, 95% CI [0.036, 0.098], and 14 months postpartum, indirect effect ab = 0.043, 95% CI [0.023, 0.067]. These effects remained stable even when adjusting for potential confounders. Key Conclusions: This study suggests that the association between FOC and mother-child-bonding is mediated by birth experience, pointing to the importance of a woman's positive subjective experience. Implications for Practice: Findings reveal two targets for peripartum interventions for women at risk for poor mother-child-bonding, namely the implementation of FOC screenings during pregnancy, and birth experience as mediating factor between FOC and mother-child-bonding. Focusing on the mother's subjective birth experience could aid to identify women at risk for impaired bonding who might need additional support. [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]

Extensive literature has shown that interparental conflicts and violence have detrimental effects on children's adjustment in childhood and adolescence. It is not equally well-understood how parental relationship satisfaction impacts infant communicational and personal-social development during the first year of life. This longitudinal study examines (a) the impact of maternal and paternal relationship satisfaction on infant development, (b) whether this prospective association is mediated by parent-infant relationship, and (c) a potential moderating effect of infant gender. Data were derived from the population-based cohort study "Dresden Study on Parenting, Work, and Mental Health" (DREAM) including 1,012 mothers and 676 fathers. Relationship satisfaction and parent-infant relationship were assessed eight weeks postpartum, infant communicational and personal-social development were measured 14 months postpartum. Multiple linear regression, mediation, and moderation analyses were conducted for mothers and fathers separately. It was shown that paternal relationship satisfaction is a significant predictor of infant personal-social development. This prospective association was partially mediated by father-infant relationship. When postnatal depression was included in the analysis, however, father-infant relationship was not a significant mediator. The association in fathers is neither reduced nor increased as a function of infant gender. No similar effects were found in the mothers' sample. Parental relationship satisfaction did not significantly predict infant communicational development in either mothers or fathers. The study findings highlight the importance of paternal relationship satisfaction, father-infant relationship, and postnatal depression for infant personal-social development. [ABSTRACT FROM AUTHOR]

Background: Father-infant bonding is important for child development. Yet, in contrast to mother-infant bonding, little is known about factors that might facilitate father-infant bonding. With new generations of fathers being more involved in childcare, this study aims to examine the impact of paternal leave duration on father-infant bonding, and whether this relation is mediated by the amount of time fathers actively spend on childcare. Methods: Data of n = 637 fathers were derived from the German population-based cohort study "Dresden Study on Parenting, Work, and Mental Health" (DREAM). Mediation analyses were conducted. Duration of paternal leave (predictor), weekly hours spent on childcare (mediator), and father-infant bonding (outcome) were measured at 14 months postpartum. The potential confounders current status of paternal leave, part-time work during paternal leave, duration of solo paternal leave, age, education, and partnership satisfaction were included in a second mediation analysis. Results: Without considering confounders, duration of paternal leave positively predicted father-infant bonding through weekly hours spent on childcare. When adding confounders to the model, this indirect path did not stay significant. Moreover, in the adjusted model and on the direct path duration of paternal leave negatively predicted father-infant bonding. Additionally, partnership satisfaction positively predicted father-infant bonding. Some study variables were significantly associated with the mediator. Longer duration of paternal leave, currently being on paternal leave, younger age, and lower educational level predicted more weekly hours spent on childcare. Conclusions: Duration of paternal leave not being a stable predictor for father-infant bonding suggests that fathers, who do not have the opportunity to take long periods of paternal leave, can still form strong bonds with their infants. Other factors, for example partnership satisfaction, which might represent fathers' underlying capacity to bond, might be more crucial for father-infant bonding. At the same time, results should not be interpreted in a way that father involvement (e.g., paternal leave/time spent) does not matter for children's development. The finding that longer duration of paternal leave increases weekly hours spent on childcare supports the idea that facilitating father involvement can be achieved by paternal leave incentives such as non-transferable father months. [ABSTRACT FROM AUTHOR]

Introduction: Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder that occurs following the administration of heparin and is caused by antibodies to platelet factor 4 and heparin. Diagnosis of HIT is essential to guide treatment strategies using non-heparin anticoagulants and to avoid unwanted and potential fatal thromboembolic complications. This consensus statement, formulated by members of the Thrombosis and Haemostasis Society of Australia and New Zealand, provides an update on HIT pathogenesis and guidance on the diagnosis and management of patients with suspected or confirmed HIT.Main Recommendations: A 4Ts score is recommended for all patients with suspected HIT prior to laboratory testing. Further laboratory testing with a screening immunoassay or confirmatory functional assay is not recommended in individuals with a low 4Ts score. However, if there are missing or unreliable clinical data, then laboratory testing should be performed. A positive functional assay result confirms the diagnosis of HIT and should be performed to confirm a positive immunoassay result. Heparin exposure must be ceased in patients with suspected or confirmed HIT and initial treatment with a non-heparin alternative instituted. Non-heparin anticoagulants (danaparoid, argatroban, fondaparinux and bivalirudin) used to treat HIT should be given in therapeutic rather than prophylactic doses. Direct oral anticoagulants may be used in place of warfarin after patients with HIT have responded to alternative parenteral anticoagulants with platelet count recovery.Changes in Management AsA Result Of This Statement: These are the first Australasian recommendations for diagnosis and management of HIT, with a focus on locally available diagnostic assays and therapeutic options. The importance of examining both clinical and laboratory data in considering a diagnosis of HIT cannot be overstated. [ABSTRACT FROM AUTHOR]

Intimate partner violence (IPV) affects individuals and families from all backgrounds, regardless of their ethnicity, socio-economic status, sexual orientation, or religion. Pregnancy and childbirth could be a time of vulnerability to violence because of changes in physical, emotional, social, and economic demands and needs. Prevalence of IPV against women during the perinatal period is increasingly researched and documented. However, evidence on IPV prevalence among intimate partners as well as on the course of IPV over the perinatal period is scarce. The purpose of this review was to provide a narrative synthesis of the existing literature regarding the prevalence estimates of IPV among intimate partners over the perinatal period. Through this review, we also gained better insight into associated factors, as well as the various forms of IPV. Of the 766 studies assessing prevalence estimates identified, 86 were included, where 80 studies focused on unidirectional IPV (i.e., perpetrated by men against women) and six studies investigated bidirectional IPV (i.e., IPV perpetrated by both partners). Most of the included studies reported lower overall prevalence rates for unidirectional IPV postpartum (range: 2–58%) compared to pregnancy (range: 1.5–66.9%). Psychological violence was found to be the most prevalent form of violence during the entire perinatal period. Studies on bidirectional IPV mostly reported women's perpetration to be almost as high as that of their partner or even higher, yet their findings need to be interpreted with caution. In addition, our results also highlighted the associated factors of IPV among partners, in which they were assimilated into a multi-level ecological model and were analyzed through an intersectional framework. Based on our findings, IPV is found to be highly prevalent during the entire perinatal period and in populations suffering from social inequalities. Further research exploring not only the occurrence, but also the motivations and the context of the bidirectionality of IPV during the perinatal period may facilitate better understanding of the detrimental consequences on partners and their families, as well as the development of effective intervention strategies. Public health prevention approaches intervening at optimal times during the perinatal period are also needed. [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]

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]

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]

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.

Background: The evidence on coagulation changes with frailty is not consistent and clinical studies suggest that frail older people may be at an increased risk of bleeding complications with anticoagulant therapy. Aims: This study aims to assess the impact of frailty on coagulation function and on response to warfarin. Methods: Inpatients aged over 65 years with atrial fibrillation (AF) were recruited. Frailty was determined using the Reported Edmonton Frail Scale. The Overall Haemostatic Potential (OHP) and Calibrated Automated Thrombogram (CAT) were used to globally assess coagulation function. Results: Data of 95 participants were analysed, mean age 85.5 ± 6.2, 40% female, and 50.5% frail. Among participants not on anticoagulants ( N = 36), there was an increased fibrin generation and decreased thrombin generation compared to the local established normal ranges in young healthy volunteers; the frail had significantly reduced fibrin generation compared to the non-frail. In the warfarin-treated group ( N = 59), there was no difference on coagulation profiles between the frail and the non-frail from any of the coagulation tests. Conclusion: In this cohort of acute hospitalised patients with AF, the observed decreased fibrin generation in the frail may reflect decreased acute phase response as suggested with the lower plasma fibrinogen in that group. There was no difference in coagulation profiles between the frail and the non-frail amongst those taking warfarin. Compared to young healthy volunteers, older inpatients had increased fibrin generation and decreased thrombin generation. The findings reflect the complex interaction between age, frailty, acute illness, and coagulation. [ABSTRACT FROM AUTHOR]

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]

The steady-state operation of Chinese hamster ovary (CHO) cells in perfusion bioreactors requires the equilibration of reactor dynamics and cell metabolism. Accordingly, in this work we investigate the transient cellular response to changes in its environment and their interactions with the bioreactor hydrodynamics. This is done in a benchtop perfusion bioreactor using MALDI-TOF MS through isotope labeling of complex intracellular nucleotides (ATP, UTP) and nucleotide sugars (UDP-Hex, UDP-HexNAc). By switching to a 13C6 glucose containing feed media during constant operation at 20 × 106 cells and a perfusion rate of 1 reactor volume per day, isotopic steady state was studied. A step change to the 13C6 glucose medium in spin tubes allowed the determination of characteristic times for the intracellular turnover of unlabeled metabolites pools [ABSTRACT FROM AUTHOR]

Perfusion cell culture processes allow the steady-state culture of mammalian cells at high viable cell density, which is beneficial for overall product yields and homogeneity of product quality in the manufacturing of therapeutic proteins. In this study, the extent of metabolic steady state and the change of the metabolite profile between different steady states of an industrial Chinese hamster ovary (CHO) cell line producing a monoclonal antibody (mAb) was investigated in stirred tank perfusion bioreactors. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) of daily cell extracts revealed more than a hundred peaks, among which 76 metabolites were identified by tandem MS (MS/MS) and high resolution Fourier transform ion cyclotron resonance (FT-ICR) MS. Nucleotide ratios (Uridine (U)-ratio, nucleotide triphosphate (NTP)-ratio and energy charge (EC)) and multivariate analysis of all features indicated a consistent metabolite profile for a stable culture performed at 40 × 106 cells/mL over 26 days of culture. Conversely, the reactor was operated continuously so as to reach three distinct steady states one after the other at 20, 60, and 40 × 106 cells/mL. In each case, a stable metabolite profile was achieved after an initial transient phase of approximately three days at constant cell density when varying between these set points. Clear clustering according to cell density was observed by principal component analysis, indicating steady-state dependent metabolite profiles. In particular, varying levels of nucleotides, nucleotide sugar, and lipid precursors explained most of the variance between the different cell density set points. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:879-890, 2017 [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]

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]

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]

ABSTRACT Bernard-Soulier syndrome ( BSS) is a rare autosomal recessive bleeding disorder characterized by defects of the GPIb-IX-V complex, a platelet receptor for von Willebrand factor ( VWF). Most of the mutations identified in the genes encoding for the GP1BA (GPIbα), GP1BB (GPIbβ), and GP9 (GPIX) subunits prevent expression of the complex at the platelet membrane or more rarely its interaction with VWF. As a consequence, platelets are unable to adhere to the vascular subendothelium and agglutinate in response to ristocetin. In order to collect information on BSS patients, we established an International Consortium for the study of BSS, allowing us to enrol and genotype 132 families (56 previously unreported). With 79 additional families for which molecular data were gleaned from the literature, the 211 families characterized so far have mutations in the GP1BA (28%), GP1BB (28%), or GP9 (44%) genes. There is a wide spectrum of mutations with 112 different variants, including 22 novel alterations. Consistent with the rarity of the disease, 85% of the probands carry homozygous mutations with evidence of founder effects in some geographical areas. This overview provides the first global picture of the molecular basis of BSS and will lead to improve patient diagnosis and management. [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]

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]

PurposeDiabetes and cardiovascular disease are major public health concerns worldwide and are leading causes of morbidity and mortality. People with type 2 diabetes are at an increased risk for cardiovascular disease. Diet has a substantial affect on the progression of many diseases, including diabetes, cardiovascular disease, osteoporosis, and arthritis. Omega-3 polyunsaturated fatty acids (long-chain polyunsaturated fatty acids [LC-PUFA]) have long been attributed to the maintenance of health and may be of benefit in reducing cardiovascular risk. The purpose of this review is to investigate the possible roles of omega-3 in reducing cardiovascular risk in patients with diabetes.MethodsA literature search was conducted from the Medline, EBSCO, and EMBASE databases. Articles that addressed diabetes, cardiovascular disease, or omega-3 were included.ResultsReviews and studies reported an association with fish and omega-3 LC-PUFA consumption and decreased total cardiovascular mortality (approximately 15%-19%), along with decreased platelet activation and aggregation, improved lipid profiles, including reduction of triglycerides and very low-density lipoprotein (VLDL), decreased inflammation, and lowered blood pressure.ConclusionDiets higher in fish and omega-3 LC-PUFA may reduce cardiovascular risk in diabetes by inhibiting platelet aggregation, improving lipid profiles, and reducing cardiovascular mortality. Fish and omega-3 LC-PUFA can be recommended to people with diabetes and included into a diabetes management program. [ABSTRACT FROM PUBLISHER]

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

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]

The National Socialist Government of Germany has as one of its avowed aims the improvement of the biological and racial qualities of the German people. For this purpose, it has undertaken a variety of measures, carried or as part of the public health and social welfare services of the state. Three out of every hundred Germans are afflicted with physical and mental diseases which are believed to be hereditary, and which seriously interfere with their ability to earn a livelihood. In some sections of the country, hereditary feeblemindedness afflicts about six out of every thousand inhabitants. Hence, a sterilization law has been passed. The German sterilization law is not a hasty enactment, as some people believe. Educational work along eugenic lines goes back four decades. Application for sterilization can be made by the afflicted person himself, by his guardian in the case of minors and incompetents, by the local public health office, or by superintendents of insane asylums, prisons, or homes for the feeble-minded.

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]

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