Nuclear segmentation facilitates neutrophil migration.

Neutrophils are among the fastest-moving immune cells. Their speed is critical to their function as 'first responder' cells at sites of damage or infection, and it has been postulated that the unique segmented nucleus of neutrophils functions to assist their rapid migration. Here, we tested this hypothesis by imaging primary human neutrophils traversing narrow channels in custom-designed microfluidic devices. Individuals were given an intravenous low dose of endotoxin to elicit recruitment of neutrophils into the blood with a high diversity of nuclear phenotypes, ranging from hypo- to hyper-segmented. Both by cell sorting of neutrophils from the blood using markers that correlate with lobularity and by directly quantifying the migration of neutrophils with distinct lobe numbers, we found that neutrophils with one or two nuclear lobes were significantly slower to traverse narrower channels, compared to neutrophils with more than two nuclear lobes. Thus, our data show that nuclear segmentation in primary human neutrophils provides a speed advantage during migration through confined spaces.

Towards Integrated Youth Care: A Systematic Review of Facilitators and Barriers for Professionals.

To overcome fragmentation in support for children and their families with multiple and enduring problems across life domains, professionals increasingly try to organize integrated care. However, it is unclear what facilitators and barriers professionals experience when providing this integrated care. Our systematic review, including 55 studies from a broad variety of settings in Youth Care, showed that integrated care on a professional level is a multi-component entity consisting of several facilitators and barriers. Findings were clustered in seven general themes: 'Child's environment', 'Preconditions', 'Care process', 'Expertise', 'Interprofessional collaboration', 'Information exchange', and 'Professional identity'. The identified facilitators and barriers were generally consistent across studies, indicating broad applicability across settings and professional disciplines. This review clearly shows that when Youth Care professionals address a broad spectrum of problems, a variety of facilitators and barriers should be considered.Registration PROSPERO, registration number CRD42018084527.

Study protocol for the randomized controlled EVA (early vascular adjustments) trial: tailored treatment of mild hypertension in pregnancy to prevent severe hypertension and preeclampsia.

BACKGROUND: In contrast to severe gestational hypertension, it is questioned whether antihypertensive medication for mild to moderate gestational hypertension prevents adverse maternal and offspring outcomes. Hypertensive drugs halve the risk of severe hypertension, but do not seem to prevent progression to preeclampsia or reduce the risk of complications in offspring. In fact, beta-blockers, a first line therapy option, are suspected to impair foetal growth. Disappointing effects of antihypertensive medication can be anticipated when the pharmacological mode of action does not match the underlying haemodynamic imbalance. Hypertension may result from 1) high cardiac output, low vascular resistance state, in which beta blockade is expected to be most effective, or 2) low cardiac output, high vascular resistance state where dihydropyridine calcium channel blockers or central-acting alpha agonists might be the best corrective medication. In the latter, beta-blockade might be maternally ineffective and even contribute to impaired foetal growth by keeping cardiac output low. We propose a randomized controlled trial to determine whether correcting the haemodynamic imbalance in women with mild to moderate hypertension reduces the development of severe hypertension and/or preeclampsia more than non-pharmacological treatment does, without alleged negative effects on foetal growth. METHODS: Women diagnosed with mild to moderate hypertension without proteinuria or signs of other organ damage before 37 weeks of pregnancy are invited to participate in this randomized controlled trial. Women randomized to the intervention group will be prescribed tailored antihypertensive medication, using a simple diagnostic and treatment algorithm based on the mean arterial pressure/heart rate ratio, which serves as an easy-to-determine proxy for maternal circulatory state. Women randomized to the control group will receive non-pharmacological standard care according to national and international guidelines. In total, 208 women will be randomized in a 1:1 ratio. The primary outcome is progression to severe hypertension and preeclampsia and the secondary outcomes are adverse maternal and neonatal outcomes. DISCUSSION: This trial will provide evidence of whether tailoring treatment of mild to moderate gestational hypertension to the individual haemodynamic profile prevents maternal disease progression. TRIAL REGISTRATION: NCT02531490 , registered on 24 August 2015.

Robust and Scalable Angiogenesis Assay of Perfused 3D Human iPSC-Derived Endothelium for Anti-Angiogenic Drug Screening.

To advance pre-clinical vascular drug research, in vitro assays are needed that closely mimic the process of angiogenesis in vivo. Such assays should combine physiological relevant culture conditions with robustness and scalability to enable drug screening. We developed a perfused 3D angiogenesis assay that includes endothelial cells (ECs) from induced pluripotent stem cells (iPSC) and assessed its performance and suitability for anti-angiogenic drug screening. Angiogenic sprouting was compared with primary ECs and showed that the microvessels from iPSC-EC exhibit similar sprouting behavior, including tip cell formation, directional sprouting and lumen formation. Inhibition with sunitinib, a clinically used vascular endothelial growth factor (VEGF) receptor type 2 inhibitor, and 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), a transient glycolysis inhibitor, both significantly reduced the sprouting of both iPSC-ECs and primary ECs, supporting that both cell types show VEGF gradient-driven angiogenic sprouting. The assay performance was quantified for sunitinib, yielding a minimal signal window of 11 and Z-factor of at least 0.75, both meeting the criteria to be used as screening assay. In conclusion, we have developed a robust and scalable assay that includes physiological relevant culture conditions and is amenable to screening of anti-angiogenic compounds.

Homeostatic model assessment of beta cell function predicting abnormal oral glucose tolerance testing in pregnancy: a systematic review and meta-analysis.

BACKGROUND: Gestational diabetes mellitus (GDM) complicates 1-14% of pregnancies and relates to increased risk of adverse obstetric outcomes. Currently GDM is diagnosed using an oral glucose tolerance test (OGTT), which is burdensome and time intensive. OBJECTIVE: To compare current literature on whether the homeostatic model assessment beta cell function (HOMA-ß) is an accurate predictor of an abnormal OGTT in pregnant women. METHODS: Pubmed, Cochrane and Embase were searched. Included studies evaluated pregnant women at risk for GDM using the homeostatic model assessment of beta cell function (HOMA-ß) for the assessment of beta cell function and the OGTT. Studies with animals, non-pregnant women, women with type 2 diabetes and post-partum diabetes were excluded. The QUADAS-2 criteria were used to assess the methodological quality of studies. RESULTS: A total of 12 studies were included, reporting on 7292 women. Seven studies showed a difference in beta cell function between women with impaired glucose tolerance compared to healthy pregnant women. HOMA-ß is significantly lower in impaired glucose tolerance (p < 0.001). CONCLUSIONS: Although HOMA-ß is lower in women with abnormal OGTT in pregnancy, given the high degree of heterogeneity of studies, we do not propagate HOMA-ß as a sole diagnostic tool replacing OGTT to diagnose GDM.

The relation of standardized mental health screening and categorical assessment in detained male adolescents.

Having an effective triage tool is an important step toward a careful use of the restricted time and qualified personnel to perform comprehensive psychiatric assessment in juvenile justice settings. The aims of this study were to examine the construct validity of the Massachusetts Youth Screening Inventory-second version (MAYSI-2), and its likelihood to identify youths who might have a psychiatric disorder. Data from up to 781 male adolescents (mean age = 16.73 years) were gathered as part of the standardized mental health screening and assessment in two all-male Youth Detention Centers in the Netherlands. Categorical assessments were based on two structured diagnostic interviews. Sensitivity, specificity, positive and negative predictive values, and the area under the curve were calculated to evaluate the likelihood of the MAYSI-2 to identify youths with a psychiatric disorder. Youths with a disorder scored significantly higher on the corresponding MAYSI-2 subscale than youths without a disorder. In the total sample, 70 % of the youths with a disorder met the Caution cut-off criteria on at least one MAYSI-2 scale, while youths without a psychiatric disorder were very unlikely to meet cut-off criteria for multiple MAYSI-2 scales. Overall, the sensitivity was slightly better when analyses were repeated in groups of youths from various ethnic origins. The findings supported the construct validity of the Dutch MAYSI-2 and suggested that the MAYSI-2 is a valid mental health screening tool that may serve relatively well as a triage tool. Its effectiveness, however, may differ between ethnic groups.

The association between childhood maltreatment, mental health problems, and aggression in justice-involved boys.

The link between childhood maltreatment and adolescent aggression is well documented; yet, studies examining potential mechanisms that explain this association are limited. In the present study, we tested the association between childhood maltreatment and adolescent aggression in boys in juvenile justice facilities (N = 767) and examined the contribution of mental health problems to this relationship. Data on childhood maltreatment, mental health problems, and aggression were collected by means of self-report measures and structural equation models were used to test mediation models. We found that mental health problems mediated the link between maltreatment and aggression. Results demonstrated different pathways depending on the type of aggression examined. The association between childhood maltreatment and reactive aggression was fully mediated by a variety of mental health problems and for proactive aggression the association was partially mediated by mental health problems. We also found that reactive and proactive aggression partially mediated the association between maltreatment and mental health problems. These findings suggest that a transactional model may best explain the negative effects of childhood trauma on mental health problems and (in particular reactive) aggression. In addition, our findings add to the existing evidence that reactive and proactive aggression have different etiological pathways.

Relational security: conceptualization and operationalization in small-scale, strengths-based, community-embedded youth justice facilities.

BACKGROUND: Given the developmental vulnerability of justice-involved youth, providing a safe environment in secure facilities is a paramount, yet challenging task. Within this complexity, a sound security framework is key. The security framework exists on three dimensions: physical, procedural and relational security. Existing knowledge points at the importance of a shift in focus on physical and procedural security towards relational security as the core of the security framework. At the same time there is a dearth of knowledge on relational security, particularly in the context of youth justice. This paper explores relational security and its working mechanisms in practice. METHODS: This paper draws on findings of a comprehensive three-year evaluation of three small-scale, community-embedded facilities that are grounded in relational security. The approach of the evaluation was derived from action research, involving a cyclic process alternating between action, research and critical reflection, while engaging all stakeholders in the research process. The action research cycle involved qualitative research (a total of 63 semi-structured interviews) incorporating the perspective of staff, youth and parents. RESULTS: Relational security is grounded in three distinct, but interrelated, elements - staff's basic attitude, a constructive alliance between staff and youth, staff presence - and promotes a safe and therapeutic environment through several mechanisms. CONCLUSIONS: Relational security can be defined in a practical conceptualization; outlining a way of working that guides staff in how to establish a safe and therapeutic environment in secure facilities. This conceptualization finds support in the well-established literature covering the therapeutic alliance and can be substantiated by two aligning theories concerning youth justice strategies: social-ecological theory and self-determination theory. Relational security is not only a way of working, but also a way of being. It encompasses a vision about security and mentality towards justice-involved youth that sees them not merely as 'risks to be managed', but primarly as 'resources to be developed'.

A Tailored Approach for Justice Involved Youth With an Intellectual Disability: The Suitability of a Small-Scale Community-Integrated Approach.

Youngsters with intellectual disabilities are overinvolved within the youth justice system. The aim of this study was to explore the suitability of a small-scale community-integrated approach for justice involved youngsters with intellectual disabilities. This study compared the numbers of transfers, the number, type, and rate of change in incidents, and the possible mediating effect of resilience thereon, between 40 youngsters with and 19 youngsters without intellectual disabilities, placed in a small-scale facility. There were no differences in the number of transfers, the number, type, and rate of change in incidents, and no mediating effect of resilience was found. A small-scale community integrated approach for youth justice facilities can be suited to provide tailored placement for youngsters with intellectual disabilities, given the presence of protective factors and motivation. Both youngsters with and without intellectual disabilities showed a low number of incidents and were able to continue or initiate structural daytime activities.

Negative impact of non-evidence-based information received by women taking antidepressants during pregnancy from health care providers and others.

OBJECTIVES: The use of antidepressants by women during pregnancy continues to be a controversial subject, with conflicting information regarding the safety of this group of drugs. We sought (1) to determine the impact of information, advice, and comments women received from health care providers, family, and media about use of antidepressants during pregnancy, and (2) to compare experiences regarding the psychosocial impact of women who continued and discontinued antidepressant therapy during pregnancy. METHODS: Women who had taken an antidepressant at some point during pregnancy were interviewed. The responses of women who continued antidepressant therapy throughout pregnancy were compared with those of women who discontinued therapy at some point in the pregnancy. A questionnaire with questions pertaining to information women had received from various individuals regarding the use of an antidepressant while pregnant was administered to both groups. RESULTS: Ninety-four interviews were completed; 78 were with women who continued antidepressant therapy throughout pregnancy, and 16 were with women who discontinued therapy. The small number of women in the discontinuation group was a result of many women declining to participate. More than one half of the women who continued the medication throughout pregnancy had frequently considered discontinuing, despite reassurance that continuation would cause no harm to their baby. Negative information was recalled far more often than reassuring information. CONCLUSION: Information from friends, family, and health care providers can have a negative impact on decision-making regarding pharmacotherapy for depression during pregnancy. Health care providers should be cognizant of this when counselling patients who require antidepressant therapy during pregnancy.

Recidivism in subgroups of serious juvenile offenders: different profiles, different risks?

BACKGROUND: Research has shown that the treatment of juvenile offenders is most effective when it takes into account the possible risk factors for re-offending. It may be asked whether juvenile offenders can be treated as one homogeneous group, or, if they are divisible into subgroups, whether different risk factors are predictive of recidivism. AIMS AND HYPOTHESES: Our aims were to find out whether serious juvenile offenders may be subdivided into clearly defined subgroups and whether such subgroups might differ in terms of the risk factors that predict recidivism. METHODS: In a sample of 1111 serious juvenile offenders, latent class analysis was used to identify subgroups. For each juvenile offender, 70 risk factors were registered. Severity of recidivism was measured on a 12-point scale. Analysis was then conducted to identify the risk factors that best predicted the different patterns of recidivism. RESULTS: Four distinct subgroups of juvenile offenders were identified: serious violent offenders, violent property offenders, property offenders, and sex offenders. Violent property offenders were the most serious recidivists and had the highest number of risk factors. Serious violent offenders and property offenders were characterised by overt and covert behaviour, respectively. Sex offenders differed from the other three groups in the rarity of their recidivism and in the risk factors that are present. For each of these four subgroups, a different set of risk factors was found to predict severity of recidivism. CONCLUSIONS: Differences in recidivism rates occurred in spite of the fact that most of these youngsters had been in the standard treatment programme offered to serious juvenile offenders in the Netherlands. This was not a treatment outcome study, but the indication that two of the groups identified in our study appeared to be worse after going through this programme, whereas the other two did quite well in terms of recidivism lends weight to our idea that such classification of juvenile offenders may lead to more targeted treatment programmes that would better serve both the general public and the youths concerned.

Negative Third-Party Reactions to Male and Female Victims of Rape: The Influence of Harm and Normativity Concerns.

Male and female victims of sexual violence frequently experience secondary victimization in the form of victim blame and other negative reactions by their social surroundings. However, it remains unclear whether these negative reactions differ from each other, and what mechanisms underlie negative reactions toward victims. In one laboratory study (N = 132) and one online study (N = 421), the authors assessed participants' reactions to male and female victims, and whether different (moral) concerns underlay these reactions. The reactions addressed included positive and negative emotions, behavioral and characterological blame, explicit and implicit derogation, and two measures of distancing. It was hypothesized that male victimization would evoke different types of (negative) reactions compared with female victimization, and that normative concerns would predict a greater proportion of the variance of reactions to male victims than female victims. Multivariate analyses of variance (MANOVAs) were conducted to test whether reactions to male and female (non-)victims differed. Multiple regression analyses were conducted to test the influence of gender traditionality, homonegativity, as well as binding and individualizing moral values on participants' reactions. Results revealed that participants consistently reacted more negatively to victims than to nonvictims, and more so to male than to female targets. Binding values were a regular predictor of negative reactions to victims, whereas they predicted positive reactions to nonvictims. The hypothesis that different mechanisms underlie reactions to male versus female victims was not supported. The discussion addresses implications of this research for interventions targeting secondary victimization and for future research investigating social reactions to victims of sexual violence. It also addresses limitations of the current research and considerations of diversity.

Toward a Tailored Model of Youth Justice: A Qualitative Analysis of the Factors Associated with Successful Placement in a Community-Integrated Facility.

Community-integrated facilities provide security and care for justice-involved youth, minimizing risks, while allowing youth to build on protective factors within their community. Literature on the specific factors that determine appropriate placement in a community-integrated facility, versus a more restrictive high-security setting, is scarce. Current screening and assessment tools for youth are mostly applied after placement and mainly focus on the reoffending risk. The current paper explored which youth, who would previously have been placed in a high-security setting, could be successfully placed in a less secure community-integrated facility. Through qualitative analysis, based on the perspectives of professionals, youth and parents, the current paper identified six distinct domains to guide appropriate screening and outlines guidelines for policy and practice. These domains include: motivation to comply, short and long-term perspective, current offense context, crime history, safety and support from youth's network, and mental health and intellectual abilities.

Risk Assessment in Juvenile and Young Adult Offenders: Predictive Validity of the SAVRY and SAPROF-YV.

Most juvenile risk assessment tools heavily rely on a risk-focused approach. Less attention has been devoted to protective factors. This study examines the predictive validity of protective factors in addition to risk factors, and developmental differences in psychometric properties of juvenile risk assessment. For a national Dutch sample of 354 juvenile and young adult offenders (16-26 years) risk and protective factors were retrospectively assessed at discharge from seven juvenile justice institutions, using the Structured Assessment of Violence Risk in Youth (SAVRY) and Structured Assessment of Protective Factors for violence risk - Youth Version (SAPROF-YV). Results show moderate validity for both tools predicting general, violent, and nonviolent offending at different follow-up times. The SAPROF-YV provided incremental predictive validity over the SAVRY, and predictive validity was stronger for younger offenders. Evidently both the SAVRY and SAPROF-YV seem valid tools for the assessment of recidivism risk in juvenile and young adult offenders. Results highlight the importance of protective factors, especially in juvenile offenders, emphasizing the need for a balanced risk assessment.

Inappropriate left ventricular mass after HELLP syndrome inappropriate LVM after HELLP syndrome.

OBJECTIVES: Excessive left ventricular mass (LVM) results in inefficient LV work with energy waste leading to a negative prognostic effect. We aimed at investigating the presence of inappropriate LVM and calculating the myocardial mechano-energetic efficiency index (MEEi) in former pre-eclamptic (PE) women (with or without HELLP syndrome) compared to women who experienced HELLP syndrome without PE. STUDY DESIGN: In this cross-sectional study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent echocardiography as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. MAIN OUTCOME MEASURES: LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was considered as the ratio between stroke work and "double product" (to approximate energy consumption), indexed to LVM. RESULTS: LV hypertrophy was present in 8-14% and concentric remodeling in 31-42% of women, without intergroup difference. LVM was inappropriate in one-third of normotensive former HELLP and in about one-half of PE with or without HELLP, with no difference among groups. Accordingly, without nominal difference, MEEi showed a tendency towards lower values in former pre-eclamptic individuals. CONCLUSIONS: Women with a history of HELLP syndrome, independently from the presence/absence of PE, showed inappropriate LVM in the first 4 years after delivery, which may partially explain the elevated CV risk in these women compared to the general female population.

Role of Beta Cell Function and Insulin Resistance in the Development of Gestational Diabetes Mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy complication characterized by second trimester hyperglycemia. Untreated, GDM is related to an increased risk for adverse pregnancy outcomes. Both beta cell dysfunction and insulin resistance underlie impaired glucose tolerance. Understanding the dominant mechanism predisposing to GDM may be important to provide effective treatment in order to improve perinatal outcomes. We hypothesize that insulin resistance rather that beta cell dysfunction predisposes to GDM. METHODS: A 75g oral glucose tolerance test (OGTT) was performed on 2112 second-trimester pregnant women to determine the relationship between insulin resistance (HOMA-IR), beta cell function (HOMA-ß), and the prevalence of abnormal glucose handling. RESULTS: High insulin resistance raised the risk of GDM (relative risk (RR) 6.1, 95% confidence interval (CI) (4.4-8.5)), as did beta cell dysfunction (RR 3.8, 95% CI (2.7-5.4)). High insulin resistance, but not beta cell function, enhances the necessity for additional glucose lowering medication on top of a low carbohydrate diet in women diagnosed with GDM. CONCLUSIONS: Both high insulin resistance and beta cell dysfunction increase the risk of GDM. As increased insulin resistance, rather than beta cell function, is related to an insufficient response to a low carbohydrate diet, we speculate that insulin sensitizers rather than insulin therapy may be the most targeted therapeutic modality in diet-insensitive GDM.

Blood pressure adjustments throughout healthy and hypertensive pregnancy: A systematic review and meta-analysis.

Gestational hypertensive complications are preceded by deviant hemodynamic adjustments affecting blood pressure. Our objective was to determine the timing and magnitude of changes in blood pressure during singleton normotensive and hypertensive pregnancies. PubMed (NCBI) and Embase (Ovid) databases were searched for relevant studies up to November 2019. Studies reporting original blood pressure measurements during pregnancy together with a non-pregnant reference measurement were included. Studies including women with a history of cardiovascular or metabolic disease, or women using antihypertensive drugs were excluded. Pooled mean differences between pregnant and non-pregnant women, and absolute blood pressure values were calculated for predefined gestational intervals in normotensive and hypertensive pregnancy, using a random-effects model. Meta-regression analysis was used to analyze group differences in adjustments. In early normotensive pregnancy, both systolic and diastolic blood pressure decreased, reaching their maximum reduction of -4 mmHg (95%CI -6 to -1 mmHg) and -4 mmHg (95%CI, -5 to -3 mmHg), respectively in the second trimester. Thereafter, blood pressure gradually increased towards non-pregnant values. All absolute blood pressure measurements throughout normotensive pregnancy were below 130/80 mmHg. In hypertensive pregnancies, only diastolic blood pressure decreased early in pregnancy. In conclusion, this meta-analysis showed a clinically moderate, but significant mid-pregnancy drop in blood pressure during normotensive pregnancy. Reference curves with absolute values underscore the current liberal cut-off limit for gestational hypertension. A lack of a mid-pregnancy systolic blood pressure drop might reflect increased vascular resistance in women destined to develop hypertensive pregnancy complications.

No accelerated arterial aging in relatively young women after preeclampsia as compared to normotensive pregnancy.

Introduction: Preeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s). Methods: Data was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models. Results: Of the 1,217 included women (age range 22-62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: -0.48%/10 years (95% CI:-0.65 to -0.30%/10 years), NGMD: -1.13%/10 years (-1.49 to -0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls (p-values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD. Conclusion: In young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries.

Maternal myocardial dysfunction after hemolysis, elevated liver enzymes, and low platelets syndrome: a speckle-tracking study.

OBJECTIVES: Pregnancy complicated by pre-eclampsia (PE) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is associated with an increased risk of cardiovascular (CV) diseases later in life. Subclinical cardiac alterations precede eminent CV diseases. Speckle-tracking echocardiography (STE) is an effective method to assess subclinical myocardial dysfunction. We performed a myocardial speckle tracking study to investigate the prevalence of subclinical myocardial dysfunction in former PE patients (with and without HELLP syndrome) compared to normotensive women affected by HELLP syndrome. METHODS: In this cross-sectional retrospective study, women with a history of normotensive HELLP (n = 32), PE without HELLP (n = 59), and PE with HELLP (n = 101) underwent conventional and STE as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. RESULTS: Women with a history of PE with HELLP syndrome were characterized by a higher prevalence of altered left ventricular circumferential and global longitudinal two-dimensional (2D) strain (74 and 20%, respectively), altered right ventricular longitudinal 2D strain (37%), and left atrial (LA) 2D strain (57%). Moreover, a higher proportion of alterations of biventricular and LA strains was also present in former PE without HELLP as well as in the normotensive HELLP group. CONCLUSIONS: In the first years after a pregnancy complicated by HELLP syndrome, irrespective of whether there was concomitant PE, a higher rate of abnormal STE myocardial function is observed. Therefore, these women may benefit from CV risk management.

Mildly Increased Renin Expression in the Absence of Kidney Injury in the Murine Transverse Aortic Constriction Model.

Cardiorenal syndrome type 2 is characterized by kidney failure as a consequence of heart failure that affects >50% of heart failure patients. Murine transverse aortic constriction (TAC) is a heart failure model, where pressure overload is induced on the heart without any systemic hypertension or its consequences. Whether renal function is altered in this model is debated, and if so, at which time post-TAC renal dysfunction starts to contribute to worsening of cardiac function. We therefore studied the effects of progressive heart failure development on kidney function in the absence of chronically elevated systemic blood pressure and renal perfusion pressure. C57BL/6J mice (N = 129) were exposed to TAC using a minimally invasive technique and followed from 3 to 70 days post-TAC. Cardiac function was determined with 3D ultrasound and showed a gradual decrease in stroke volume over time. Renal renin expression and plasma renin concentration increased with progressive heart failure, suggesting hypoperfusion of the kidney. In addition, plasma urea concentration, a surrogate marker for renal dysfunction, was increased post-TAC. However, no structural abnormalities in the kidney, nor albuminuria were present at any time-point post-TAC. Progressive heart failure is associated with increased renin expression, but only mildly affected renal function without inducing structural injury. In combination, these data suggest that heart failure alone does not contribute to kidney dysfunction in mice.