Simulation of the effect of hemolysis on thrombosis in blood-contacting medical devices.

Heart failure, broadly characterized by the gradual decline of the ability of the heart to maintain adequate blood flow throughout the body's vascular network of veins and arteries, is one of the leading causes of death worldwide. Mechanical Circulatory Support is one of the few available alternative interventions for late-stage heart failure with reduced ejection fraction. A ventricular assist device is surgically implanted and connected to the left and or right heart ventricles to provide additional bloodflow, off-loading the work required by the heart to maintain circulation. Modern mechanical circulatory support devices generate non-physiological flow conditions that can lead to the damage and rupture of blood cells (hemolysis), and the formation of blood clots (thrombosis), which pose severe health risks to the patient. It is essential to improve prediction tools for blood damage to reduce the risk of hemolysis and thrombosis. A simulation-based approach examines the interaction between hemolysis and thrombosis. Incompressible finite-volume computational fluid dynamics simulations are executed on an open-hub axial flow ventricular assist device. A continuum model of thrombosis and the intrinsic coagulation process is extended to include the effect of hemolysis. The model accounts for the effect of activation of platelets by shear stress, paracrine signaling, adhesion, and hemoglobin and ADP released during hemolysis. The effect of hemolysis with thrombosis is modelled by accounting for the hyper-adhesivity of von-Willebrand Factor on extracellular hemoglobin, and the increased rate of platelet activation induced by ADP release. Thrombosis is assessed at varying inflow rates and rotor speeds, and cases are executed where thrombosis is affected by ADP release and Hb-induced hyper-adhesivity. It is found that there is a non-negligible effect from hemolysis on thrombosis across a range of rotor speeds, and that hyperadhesivity plays a dominant role in thrombus formation in the presence of hemolysis.

Prevalence of respiratory signs in dogs with chronic gastroenteropathy in a referral population in the United Kingdom: 42 cases (2020).

OBJECTIVES: To determine the prevalence of respiratory signs in a referral population of dogs with chronic gastroenteropathy in the United Kingdom, and to describe the epidemiology and clinical presentation of the affected dogs. MATERIALS AND METHODS: Retrospective review of canine patients diagnosed with chronic gastroenteropathy in a referral centre in the United Kingdom. Data included signalment, gastrointestinal and respiratory signs, blood analysis results and, where present, diagnostic imaging techniques, endoscopy, videofluoroscopic swallow study, bronchoalveolar lavage results and treatment response. To be included, a follow-up of a minimum of 3 months was required. Cases were excluded if there was no minimum diagnostic dataset, the aetiology of the respiratory signs was other than gastrointestinal disease or a non-gastrointestinal systemic disease was the cause of the gastrointestinal signs. RESULTS: One hundred and forty-eight dogs were included and 42 (28.4%) had concurrent respiratory signs. Gagging (69%) and vomiting (52.4%) were the most common gastrointestinal signs, while coughing (50%), tachypnoea (33.3%) and reverse sneezing (30.9%) were the most common respiratory signs. Abdominal ultrasound was performed in 31 (73.8%) while CT scan was the most common modality for thoracic (62.5%) and head (21.9%) imaging. Endoscopic procedures included gastrointestinal (54.8%), bronchoscopy (19%) and rhinoscopy (23.8%). Dietary modification was the most common treatment (66.67%). Eleven dogs (26.2%) had a relapse of the respiratory signs during the follow-up period, of which, nine (81.8%) had a concurrent relapse of the gastrointestinal signs. CLINICAL SIGNIFICANCE: Concurrent respiratory signs in dogs with chronic gastroenteropathy are frequent. A clinical improvement of these respiratory signs might be achieved during the therapeutic management of gastrointestinal disorders.

Variation in the mu-opioid receptor gene (OPRM1) moderates the influence of maternal sensitivity on child attachment.

The endogenous opioid system is thought to play an important role in mother-infant attachment. In infant rhesus macaques, variation in the µ-opioid receptor gene (OPRM1) is related to differences in attachment behavior that emerges following repeated separation from the mother; specifically, infants carrying at least one copy of the minor G allele of the OPRM1 C77G polymorphism show heightened and more persistent separation distress, as well as a pattern of increased contact-seeking behavior directed towards the mother during reunions (at the expense of affiliation with other group members). Research in adult humans has also linked the minor G allele of the analogous OPRM1 A118G polymorphism with greater interpersonal sensitivity. Adopting an interactionist approach, we examined whether OPRM1 A118G genotype and maternal (in)sensitivity are associated with child attachment style, predicting that children carrying the G allele may be more likely to develop an ambivalent attachment pattern in response to less sensitive maternal care. The sample consisted of 191 mothers participating with their children (n = 223) in the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) project, a community-based, birth cohort study of Canadian mothers and their children assessed longitudinally across the child's development. Maternal sensitivity was coded from at-home mother-child interactions videotaped when the child was 18 months of age. Child attachment was assessed at 36 months using the Strange Situation paradigm. As predicted, G allele carriers, but not AA homozygotes, showed increasing odds of being classified as ambivalently attached with decreasing levels of maternal sensitivity. Paralleling earlier non-human animal research, this work provides support for the theory that endogenous opioids contribute to the expression of attachment behaviors in humans.

A systematic review of the evidence on the effect of parental communication about health and health behaviours on children's health and wellbeing.

Parents report feeling unsure how best to talk with their children about sensitive health topics and may avoid such conversations; yet if children have questions or concerns about their health, talking to a parent could enhance their health and wellbeing. We investigated the effects of parental communications about health and health behaviours on children's health and wellbeing, and explored what strategies can encourage parents to communicate about health. We conducted a systematic review and narrative synthesis of research published between January 2008 and April 2020 from five databases. Of 14,007 articles identified, 16 met inclusion criteria focusing on five topics: diet and weight (n = 5), body image (n = 2), sexual health (n = 7), physical activity (n = 1) and bullying (n = 1). Positive child outcomes were associated with positive general parent-child communication characterised by warmth, openness and allowing children choice. Conversely, hostility, negative and inconsistent messaging were associated with poorer outcomes. Interventions to increase parent-child communication could be classified as providing single directive messages, media campaigns or intensive support. Single messages increased communication frequency; media campaigns and intensive interventions showed mixed outcomes. No differences in outcomes were found according to child's gender or socio-economic status. Generally, parents were less confident in initiating, rather than continuing, conversations and were more likely to initiate conversations when they felt they had good topic knowledge. While the relatively small, diverse sample limits the strength of these findings, this review provides provisional support for approaches to promote positive parent-child communication about health that are associated with better child health and wellbeing.

Reversal of stress fibre formation by Nitric Oxide mediated RhoA inhibition leads to reduction in the height of preformed thrombi.

Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation and inhibition. We hypothesised that Nitric oxide (NO), a platelet inhibitor, can modulate the actin cytoskeleton reversing platelet spreading, and therefore reduce the capability of thrombi to withstand a high shear environment. Our data demonstrates that GSNO, DEANONOate, and a PKG-activating cGMP analogue reversed stress fibre formation and increased actin nodule formation in adherent platelets. This effect is sGC dependent and independent of ADP and thromboxanes. Stress fibre formation is a RhoA dependent process and NO induced RhoA inhibition, however, it did not phosphorylate RhoA at ser188 in spread platelets. Interestingly NO and PGI2 synergise to reverse stress fibre formation at physiologically relevant concentrations. Analysis of high shear conditions indicated that platelets activated on fibrinogen, induced stress fibre formation, which was reversed by GSNO treatment. Furthermore, preformed thrombi on collagen post perfused with GSNO had a 30% reduction in thrombus height in comparison to the control. This study demonstrates that NO can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling excessive thrombosis.

Prostacyclin reverses platelet stress fibre formation causing platelet aggregate instability.

Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear. Exploration of the molecular mechanisms underpinning this effect revealed that PGI2 reversed stress fibre formation in adherent platelets, reduced platelet spreading, whilst simultaneously promoting actin nodule formation. The effects of PGI2 on stress fibres were mimicked by the adenylyl cyclase activator forskolin and prevented by inhibitors of protein kinase A (PKA). Stress fibre formation is a RhoA dependent process and we found that treatment of adherent platelets with PGI2 caused inhibitory phosphorylation of RhoA, reduced RhoA GTP-loading and reversal of myosin light chain phosphorylation. Phospho-RhoA was localised in actin nodules with PKA type II and a number of other phosphorylated PKA substrates. This study demonstrates that PGI2 can reverse key platelet functions after their initial activation and identifies a novel mechanism for controlling thrombosis.

Experiences of remote mood and activity monitoring in bipolar disorder: A qualitative study.

BACKGROUND: Mobile technology enables high frequency mood monitoring and automated passive collection of data (e.g. actigraphy) from patients more efficiently and less intrusively than has previously been possible. Such techniques are increasingly being deployed in research and clinical settings however little is known about how such approaches are experienced by patients. Here, we explored the experiences of individuals with bipolar disorder engaging in a study involving mood and activity monitoring with a range of portable and wearable technologies. METHOD: Patients were recruited from a wider sample of 50 individuals with Bipolar Disorder taking part in the Automated Monitoring of Symptom Severity (AMoSS) study in Oxford. A sub-set of 21 patients participated in a qualitative interview that followed a semi-structured approach. RESULTS: Monitoring was associated with benefits including increased illness insight, behavioural change. Concerns were raised about the potential preoccupation with, and paranoia about, monitoring. Patients emphasized the need for personalization, flexibility, and the importance of context, when monitoring mood. CONCLUSIONS: Mobile and electronic health approaches have potential to lend new insights into mental health and transform healthcare. Capitalizing on the perceived utility of these approaches from the patients' perspective, while addressing their concerns, will be essential for the promise of new technologies to be realised.

Thinking and doing: the effects of dopamine and oxytocin genes and executive function on mothering behaviours.

Animal and human studies suggest that initial expression of maternal behaviour depends on oxytocin and dopamine systems. However, the mechanism by which these systems affect parenting behaviours and the timing of these effects are not well understood. This article explores the role of mothers' executive function in mediating the relation between oxytocin and dopamine gene variants and maternal responsiveness at 48 months post-partum. Participants (n = 157) were mothers recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study, which assesses longitudinally two cohorts of mothers and children in Canada. We examined single nucleotide polymorphisms (SNPs) related to the dopamine and oxytocin systems (DRD1 rs686, DRD1 rs265976, OXTR rs237885 and OXTR rs2254298), assessed mothers' decision-making at 48 months using the Cambridge Neurological Automated Testing Battery (CANTAB) and evaluated maternal responsiveness from videotaped interactions during the Etch-A-Sketch co-operation task. Mediation analyses showed that OXTR rs2254298 A-carriers had an indirect effect on positive parenting which was mediated by mothers' performance on decision-making task (estimate = 0.115, P < 0.005), while OXTR rs2254298 A-carriers had both direct and indirect effects on physically controlling parenting, also mediated through enhanced performance on decision-making (estimate = -0.059, P < 0.005). Dopamine SNPs were not associated with any measure of executive function or parenting (all P > 0.05). While oxytocin has previously been associated with only the early onset of maternal behaviour, we show that an OXTR polymorphism is involved in maternal behaviour at 48 months post-partum through mothers' executive function. This research highlights the importance of the oxytocin system to maternal parenting beyond infancy.

Associations between mood instability and emotional processing in a large cohort of bipolar patients.

BACKGROUND: Aberrant emotional biases have been reported in bipolar disorder (BD), but results are inconsistent. Despite the clinical relevance of chronic mood variability in BD, there is no previous research investigating how the extent of symptom fluctuations in bipolar disorder might relate to emotional biases. This exploratory study investigated, in a large cohort of bipolar patients, whether instability in weekly mood episode symptoms and other clinical and demographic factors were related to emotional bias as measured in a simple laboratory task. METHOD: Participants (N = 271, BDI = 206, BDII = 121) completed an 'emotional categorization and memory' task. Weekly self-reported symptoms of depression and mania were collected prospectively. In linear regression analyses, associations between cognitive bias and mood variability were explored together with the influence of demographic and clinical factors, including current medication. RESULTS: Greater accuracy in the classification of negative words relative to positive words was associated with greater instability in depressive symptoms. Furthermore, greater negative bias in free recall was associated with higher instability in manic symptoms. Participants diagnosed with BDII, compared with BDI, showed overall better word recognition and recall. Current antipsychotic use was associated with reduced instability in manic symptoms but this did not impact on emotional processing performance. CONCLUSIONS: Emotional processing biases in bipolar disorder are related to instability in mood. These findings prompt further investigation into the underpinnings as well as clinical significance of mood instability.

Stress Physiology in Infancy and Early Childhood: Cortisol Flexibility, Attunement and Coordination.

Research on stress physiology in infancy has assumed increasing importance due to its lifelong implications. In this review, we focus on measurement of hypothalamic-pituitary-adrenal (HPA) function, in particular, and on complementary autonomic processes. We suggest that the measure of HPA function has been overly exclusive, focusing on individual reactivity to single, pragmatically selected laboratory challenges. We advocate use of multiple, strategically chosen challenges and within-subject designs. By administering one challenge that typically does not provoke reactivity and another that does, it is possible to represent allostatic load in terms of "flexibility," the capacity to titrate response to challenge. We also recommend assessing infant reactivity in the context of the primary caregiver's physiological function. Infant-mother "attunement" is central to developmental psychology, permeating diverse developmental domains with varied consequences. A review of adrenocortical attunement suggests that attunement is a reliable process, manifest across varied populations. However, attunement appears stronger in the context of more highly stressful circumstances, such that administration of multiple, selected challenges may help evaluate the degree to which individuals titrate attunement to challenge and determine the correlates of this differential attunement. Finally, we advocate studying the "coordination" of HPA function with other aspects of stress physiology and variation in the degree of this coordination. The use of multiple stressors is important here because each stress system is differentially sensitive to different types of challenge. Therefore, use of single stressors in between-subject designs impedes full recognition of the role played by each system. Overall, we recommend measure of flexibility, attunement, and coordination in the context of multiple challenges to capture allostasis in environmental and physiological context. The simultaneous use of such inclusive and integrative metrics may yield more reliable findings than has hitherto been the case. The interrelation of these metrics can be understood in the context of the adaptive calibration model..

An exploratory study of positive and incongruent communication in young children with type 1 diabetes and their mothers.

BACKGROUND: The incidence of type 1 diabetes is increasing in young children. However, they are overlooked in treatment adherence and intervention research despite evidence that parents often experience difficulty securing their treatment cooperation, especially with the diet. We investigated positive and incongruent (i.e. the co-occurrence of contradictory verbal and non-verbal messages) communication in the mother-child dyad and their association with child adjustment and dietary adherence outcomes. METHODS: Participants were 23 6- to 8-year-old children with type 1 diabetes and their mothers. We conducted dietary adherence interviews with mothers and performed nutritional analyses to assess children's consumption of extrinsic sugars (e.g. confectionary). Mothers completed a standardized assessment of child psychological adjustment. Mothers and children engaged in a videotaped problem-solving task related to the dietary regimen, with maternal and child utterances and non-verbal behaviours analysed for positive dyadic and incongruent communication. RESULTS: Positive dyadic communication correlated with lower levels of child incongruent communication, fewer behavioural problems and better overall adjustment. Higher levels of maternal and child incongruent communication correlated with more behavioural and emotional problems and poorer overall adjustment. Higher levels of maternal incongruent communication correlated with poorer dietary adherence. CONCLUSIONS: Results converged to form a conceptually and empirically coherent pattern in that behavioural indices of poorer communication in both mother and child consistently correlated with poorer child adjustment outcomes. This study shows that specific features of dyadic, child and maternal communication could be targeted in developmentally sensitive interventions to promote positive communication in the home management of type 1 diabetes care for young children.

Exercise in pregnancy - UK women's views and experiences: results of an online survey.

UNLABELLED: Both NICE and RCOG recommend 30min of moderate physical activity, at least four times per week, for women with uncomplicated pregnancies, in all trimesters. The primary aims of this study were to establish the views of UK women regarding how much exercise they should undertake at each stage of pregnancy and whether they accumulated the recommended amount of physical activity through exercise during their current or most recent pregnancy. METHODS: An online survey was developed and advertised to women who had been or were pregnant via social media and websites related to pregnancy or parenting. Exercise was defined within the survey as including jogging, cycling, exercise classes and brisk but not gentle walking. RESULTS: 1001 women participated. 22.9% were currently pregnant, and 64.8% had been pregnant in the last three years. 38.5% of participants reported that women should exercise four or more times per week in the first trimester, and 23% in the third trimester. 21.3% reported exercising four or more times per week in their first trimester, and 11.4% in the third trimester. 46.9% reduced their exercise upon becoming pregnant, while 6.7% increased exercise and 12% stopped completely. Tiredness (62.7%), aches and pains (44.8%), morning sickness (41.4%) and worry about miscarriage (27.4%) were the most common reasons to avoid exercise. CONCLUSIONS: UK women may be unaware of the recommended levels of physical activity in pregnancy and may fail to meet recommendations through exercise. Despite no evidence of risk, women are concerned that exercise contributes to miscarriage.

Cooperation between scientists, NGOs and industry in support of sustainable fisheries: the South African hake Merluccius spp. trawl fishery experience.

This paper examines the increasingly close interaction between natural and social scientists, non-governmental organizations (NGO) and industry, in pursuit of responsible ecosystem-based management of fisheries. South Africa has committed to implementing an ecosystem approach to fisheries management. Management advice stems from multi-stakeholder representation on government-led scientific and management working groups. In the hake Merluccius capensis and Merluccius paradoxus fishery, the primary management measure is an annual total allowable catch (TAC), the level of which is calculated using a management procedure (MP) that is revised approximately every 4 years. Revision of the MP is a consultative process involving most stakeholders, and is based on simulation modelling of projected probable scenarios of resource and fishery dynamics under various management options. NGOs, such as the Worldwide Fund for Nature in South Africa (WWF-SA), have played an important role in influencing consumers, the fishing industry and government to develop responsible fishing practices that minimize damage to marine ecosystems. Cooperation between industry, government and scientists has helped to improve sustainability and facilitated the meeting of market-based incentives for more responsible fisheries. Research includes ecosystem modelling, spatial analysis and ecosystem risk assessment with increasing research focus on social and economic aspects of the fishery. A four-year cooperative experiment to quantify the effect of trawling on benthic community structure is being planned. The food requirements of top predators still need to be included in the TAC-setting formulae and more social and economic research is needed. This paper also demonstrates how NGO initiatives such as Marine Stewardship Council certification and the Southern African Sustainable Seafood Initiative, a traffic light system of classifying seafood for consumers, have contributed to responsible fishing practices, increased ecosystem research and public awareness. This fishery appears to have a good future, provided that the monitoring, control and surveillance systems continue to function, TACs remain within ecologically sustainable limits and the effective collaboration between government, industry, scientists and NGOs continues to drive positive change.

Circadian entrainment and its role in depression: a mechanistic review.

The natural rotation of the earth generates an environmental day-night cycle that repeats every 24 h. This daily transition from dawn to dusk provides one of the most important time cues to which the majority of organisms synchronise their activity. Under these conditions, natural light, a photic stimulus, provides the principal entraining cue. In mammals, an endogenous circadian pacemaker located within the suprachiasmatic nucleus (SCN) of the hypothalamus acts as a coordinating centre to align physiological activity with the environmental light-dark cycle. However, the SCN also receives regulatory input from a number of behavioural, non-photic, cues such as physical activity, social interactions and feeding routines. The unique ability of the SCN to integrate both photic and non-photic cues allows it to generate a rhythm that is tailored to the individual and entrained to the environment. Here, we review the key neurotransmitter systems involved in both photic and non-photic transmission to the SCN and their interactions that assist in generating an entrained output rhythm. We also consider the impact on health of a desynchronised circadian system with a focus on depressive affective disorders and current therapies aimed at manipulating the relationship between photic and non-photic SCN regulators.

Dopamine receptors D1 and D2 are related to observed maternal behavior.

The dopamine pathway and especially the dopamine receptors 1 and 2 (DRD1 and DRD2) are implicated in the regulation of mothering in rats. Evidence for this in humans is lacking. Here, we show that genetic variation in both DRD1 and DRD2 genes in a sample of 187 Caucasian mothers predicts variation in distinct maternal behaviors during a 30-min mother-infant interaction at 6 months postpartum. Two DRD1 single-nucleotide polymorphisms (SNPs rs265981 and rs686) significantly associated with maternal orienting away from the infant (P = 0.002 and P = 0.003, respectively), as did DRD1 haplotypes (P = 0.03). Two DRD2 SNPs (rs1799732 and rs6277) significantly associated with maternal infant-directed vocalizing (P = 0.001 and P = 0.04, respectively), as did DRD2 haplotypes (P = 0.01). We present evidence for heterosis in DRD1 where heterozygote mothers orient away from their infants significantly less than either homozygote group. Our findings provide important evidence that genetic variation in receptors critical for mothering in non-human species also affect human maternal behaviors. The findings also highlight the importance of exploring multiple dimensions of the complex human mothering phenotype.

Recommendations for patient selection in spinal cord stimulation.

Studies have shown that spinal cord stimulation (SCS) can reduce chronic pain by at least 50% over prolonged periods, improve function and quality-of-life, reduce requirements for healthcare resources and enable return to work in appropriately selected patients. However, SCS does not provide pain relief in all patients and is an expensive, labor intensive and invasive procedure with complications and ongoing management that requires specialists with specific skills and judgment. Multidisciplinary selection of appropriate patients for SCS is essential to achieve maximal benefit from the procedure. The aim of the article is to provide a clinical practice guide to the likely effectiveness of SCS in treating various types of chronic pain, as supported by the literature. The article will summarize indications and contraindications for SCS, provide guidance on the selection and timing for referral, and highlight the benefits and complications associated with the procedure.

Serotonin transporter allelic variation in mothers predicts maternal sensitivity, behavior and attitudes toward 6-month-old infants.

Maternal behavior in the new mother is a multidimensional set of responses to infant cues that are influenced by the mother's early life experiences. In this study, we wanted to test if mothers' early life experiences and mothers' genotype have interactive effects on maternal behaviors and attitudes, something which has not been previously explored. In a sample of 204 mothers, we assessed maternal genotype at the serotonin transporter-linked polymorphic region (5-HTTLPR) and an adjacent upstream polymorphism (rs25531), together giving rise to three alleles: short (S), L(G) and L(A). Controlling for maternal age and parity, we showed that this genotype can predict differences in maternal sensitivity at 6 months postpartum: mothers with an S (or the functionally similar L(G)) allele were more sensitive than mothers who lacked the allele during a 30-min recorded mother-infant interaction (F (4,140) = 3.43; P = 0.01). Furthermore, we found highly significant gene-environment interactions in association with maternal behavior, such that mothers with no S or L(G) alleles oriented away more frequently from their babies if they also reported more negative early care quality (F (5,138) = 3.28; P = 0.008). Finally, we found significant gene-environment associations with maternal attitudes; mothers with the S allele and with greater early care quality scored higher on ratings of their perceived attachment to their baby (F (5,125) = 3.27; P = 0.008). The regression results show significant interactions between the reported quality of care mothers received from their own parents and genotype on both their frequency of orienting away from the infant during the interaction (F(5, 138) = 3.28; P = 0.008, Fig. 1a) and their perceived attachment feelings to the infant (F(5, 125) = 3.27; P = 0.008, Fig. 1b); however the direction of the effects for these two outcome measures were different from one another. With increasing care quality, mothers with the L(A)L(A) genotype (no S or L(G) allele) oriented away less frequently, while S or L(G) allele carriers showed no significant change. In contrast, with increasing early care quality. L(A)L(A) (no S or L(G) allele) mothers scored lower on perceived attachment to their infants, whereas S or L(G) allele carrying mothers scored higher. [corrected].