SARS-CoV-2 pandemic as a catalyst? Development of emotional problems of preschool children of mothers with childhood maltreatment experiences in the course of the pandemic–a longitudinal analysis

BackgroundSARS-CoV-2 pandemic have posed great challenges for all families and children. Health risks and fears associated with SARS-CoV-2 negatively affect the parental mental health and perceived stress, which in turn influence parental coping and thereby impairs the mental health and well-being of their children. Additional risk factors within the parents, such as maternal childhood maltreatment (CM) experiences, may increase the risk of children to develop emotional problems during the pandemic.ObjectiveThe purpose of this longitudinal study is to determine whether preschool children of mothers with CM are at higher risk of developing emotional problems during the pandemic than preschool children of mothers without CM.Method74 mothers from a birth cohort examining pathways to resilience or vulnerability in the transgenerational transmission of CM, provided information on emotional problems of their children (aged 3–7 years) at two measurement time points (t1: May 2020, t2: March 2021) as part of an online “SARS-CoV-2 pandemic” survey. In addition, parents were asked for a retrospective assessment of their children's emotional problems before the pandemic at time t1. Children's emotional problems were assessed using the “emotional problems” scale of the German version of the Strengths and Difficulties Questionnaire (SDQ) and linked to previously collected data on mothers' childhood maltreatment experiences, which were collected using the German short version of the Trauma in Childhood Questionnaire (CTQ).ResultsOur analyses showed that children's emotional problems increased significantly over the SARS-CoV-2 pandemic [F(1.86, 116.88) = 3.72, p = 0.030 η2 = 0.06] and were rated significantly higher in the group of children of mothers with CM, than in the group of mothers without CM [F(1, 63) = 126.06, p < 0.001 η2 = 0.67]. Furthermore children's emotional problems of mothers with CM increased significantly more and reached a clinically significant value during the pandemic than for children of mothers without CM [F(1.86, 116.88) = 8.89, p < 0.001, η2 = 0.12].ConclusionsChildren of mothers with CM appear to be at increased risk of developing emotional problems during the pandemic. CM therefore needs to be considered as an additional risk factor in the impact of the pandemic on children

Aberrant phase separation of FUS leads to lysosome sequestering and acidification

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the death of upper and lower motor neurons. While most cases of ALS are sporadic, some of the familial forms of the disease are caused by mutations in the gene encoding for the RNA-binding protein FUS. Under physiological conditions, FUS readily phase separates into liquid-like droplets in vivo and in vitro. ALS-associated mutations interfere with this process and often result in solid-like aggregates rather than fluid condensates. Yet, whether cells recognize and triage aberrant condensates remains poorly understood, posing a major barrier to the development of novel ALS treatments. Using a combination of ALS-associated FUS mutations, optogenetic manipulation of FUS condensation, chemically induced stress, and pH-sensitive reporters of organelle acidity, we systematically characterized the cause-effect relationship between the material state of FUS condensates and the sequestering of lysosomes. From our data, we can derive three conclusions. First, regardless of whether we use wild-type or mutant FUS, expression levels (i.e., high concentrations) play a dominant role in determining the fraction of cells having soluble or aggregated FUS. Second, chemically induced FUS aggregates recruit LAMP1-positive structures. Third, mature, acidic lysosomes accumulate only at FUS aggregates but not at liquid-condensates. Together, our data suggest that lysosome-degradation machinery actively distinguishes between fluid and solid condensates. Unraveling these aberrant interactions and testing strategies to manipulate the autophagosome-lysosome axis provides valuable clues for disease intervention

Atypical maternal interaction is associated with elevated levels of hair cortisol in children

The quality of maternal caregiving is an important factor in the healthy development of a child. One consequence of prolonged insensitive and atypical maternal interaction behavior (e.g., withdrawing from interactions with the child and role-reversal, i.e., the takeover of the parental role or parts of it by the child) in mother-child-dyads can cause alteration of the child's stress response system. Higher salivary cortisol concentrations were reported in infants and toddlers directly after negative interactions with their parents. However, no study to date has examined the association between atypical maternal interaction behavior and hair cortisol concentrations (HCC) in infants. Here, we studied the association of maternal interaction behavior with HCC of the child. Mother-child dyads (N = 112) participated in the longitudinal study My Childhood—Your Childhood. The AMBIANCE scale and its subscales were used to assess atypical maternal interaction behavior during the Strange Situation Procedure. Chronic stress levels in the child were assessed by HCC of 3 cm hair strands at the age of 12 months. Maternal educational level (operationalized in highest education level) served as a control variable. Robust multiple linear regression analyses revealed that role/boundary confusion was associated with HCC, i.e., the higher atypical interaction behavior of the mother the higher the HCC in the children. By measuring hair cortisol in this study, it is possible to determine the average long-term activity of the child's stress response system.Thus, atypical maternal interaction behavior could be a risk factor for persistent stress in children, contributing to a higher risk for negative health outcomes in later life. The results of this study highlight the importance of early intervention programs that focus on the relationship between mother and child

Left ventricular long axis strain: a new prognosticator in non-ischemic dilated cardiomyopathy?

Background: Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. Methods and results: In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF ≤45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > −5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p  −10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. Conclusion: Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters

Fast assessment of long axis strain with standard cardiovascular magnetic resonance: a validation study of a novel parameter with reference values

Background: Assessment of longitudinal function with cardiovascular magnetic resonance (CMR) is limited to measurement of systolic excursion of the mitral annulus (MAPSE) or elaborate strain imaging modalities. The aim of this study was to develop a fast assessable parameter for the measurement of long axis strain (LAS) with CMR. Methods: 40 healthy volunteers and 125 patients with different forms of cardiomyopathy were retrospectively analyzed. Four different approaches for the assessment of LAS with CMR measuring the distance between the LV apex and a line connecting the origins of the mitral valve leaflets in enddiastole and endsystole were evaluated. Values for LAS were calculated according to the strain formula. Results: LAS derived from the distance of the epicardial apical border to the midpoint of the line connecting the mitral valve insertion points (LAS-epi/mid) proved to be the most reliable parameter for the assessment of LAS among the different approaches. LAS-epi/mid displayed the highest sensitivity (81.6 %) and specificity (97.5 %), furthermore showing the best correlation with feature tracking (FTI) derived transmural longitudinal strain (r = 0.85). Moreover, LAS-epi/mid was non-inferior to FTI in discriminating controls from patients (Area under the curve (AUC) = 0.95 vs. 0.94, p = NS). The time required for analysis of LAS-epi/mid was significantly shorter than for FTI (67 ± 8 s vs. 180 ± 14 s, p < 0.0001). Additionally, LAS-epi/mid performed significantly better than MAPSE (Delta AUC = 0.09; p < 0.005) and the ejection fraction (Delta AUC = 0.11; p = 0.0002). Reference values were derived from 234 selected healthy volunteers. Mean value for LAS-epi/mid was −17.1 ± 2.3 %. Mean values for men were significantly lower compared to women (−16.5 ± 2.2 vs. -17.9 ± 2.1 %; p < 0.0001), while LAS decreased with age. Conclusions: LAS-epi/mid is a novel and fast assessable parameter for the analysis of global longitudinal function with non-inferiority compared to transmural longitudinal strain

Optogenetic acidification of synaptic vesicles and lysosomes

Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes

Co-operation, Contestation and Complexity in Post-Conflict Security Sector Reform

Security Sector Reform (SSR) remains a key feature of peacebuilding interventions and is usually undertaken by a state alongside national and international partners. External actors engaged in SSR tend to follow a normative agenda that often has little regard for the context in post-conflict societies. Despite recurrent criticism, SSR practices of international organisations and bilateral donors often remain focused on state institutions, and often do not sufficiently attend to alternative providers of security or existing normative frameworks of security. This article provides a critical overview of existing research and introduces the special issue on “Co-operation, Contestation and Complexity in Post-Conflict Security Sector Reform”. We explore three aspects that add an important piece to the puzzle of what constitutes effective SSR. First, the variation of norm adoption, norm contestation and norm imposition in post-conflict countries that might explain the mixed results in terms of peacebuilding. Second, the multitude of different security actors within and beyond the state which often leads to multiple patterns of co-operation and contestation within reform programmes. And third, how both the multiplicity of and tension between norms and actors further complicate efforts to build peace or, as complexity theory would posit, influence the complex and non-linear social system that is the conflict-affected environment