Age differences in emotion regulation strategy use and flexibility in daily life.

OBJECTIVES: Age-related shifts in emotion regulation patterns are important for explaining preserved emotional well-being in late adulthood amidst declines in physical and cognitive health. Although several studies have examined age-related shifts in emotion regulation strategy use, age differences in how specific strategies are flexibly adapted to shifting contexts in daily life and the adaptiveness of such shifts remains poorly understood. METHODS: 130 younger adults (ages 22-35) and 130 older adults (ages 65-85) completed a modified Day Reconstruction Method Assessment and self-report questionnaires to examine age differences in emotion regulation strategy use and one aspect of emotion regulation flexibility (responsiveness) in daily life, and the adaptive implications of these differences. RESULTS: Older adults exhibited more frequent acceptance use, less frequent distraction use, and less flexibility in the responsiveness of strategies with varying negative affect. Across age groups, the use of expressive suppression and distraction was associated with less adaptive outcomes, whereas higher acceptance responsiveness, positive reappraisal responsiveness, and situation selection responsiveness were associated with more adaptive outcomes. Age-group moderated the associations between adaptiveness metrics with the use and flexibility of several emotion regulation strategies. CONCLUSION: The current findings provide early evidence of age-related decreases in emotion regulation flexibility as well as age-related shifts in the adaptiveness of emotion regulation patterns.

'You have a little human being kicking inside you and an unbearable pain of knowing there will be a void at the end': A meta-ethnography exploring the experience of parents whose baby is diagnosed antenatally with a life limiting or life-threatening condition.

BACKGROUND: Parents of babies diagnosed with life limiting conditions in the perinatal period face numerous challenges. Considerations include the remainder of the pregnancy, delivery of the baby and decisions around care in the neonatal period. AIM: To increase understanding of how parents experience the diagnosis of a life-limiting or life-threatening condition, during pregnancy and following the birth of their baby, by answering the question: 'what is known about the perinatal experiences of parents of babies with a life-limiting or life-threatening diagnosis?' DESIGN: A meta-ethnography was conducted to synthesise findings from existing qualitative evidence. DATA SOURCES: British Nursing Database, CINAHL, Medline, PsycINFO and Embase databases were searched in January 2023. FINDINGS: Relationships between parents and their families and friends, and with professionals influence the needs and experiences of parents, which oscillate between positive and negative experiences, throughout parents' perinatal palliative care journey. Parents highlighted the need for control and a sense of normality relating to their parenting experience. Validation was central to the experience of parents at all stages of parenthood. Relationships between the parent and the baby were unwavering, underpinned with unconditional love. CONCLUSION: Professionals, family members and friendship groups influence the experience, validating parents and their baby's identity and supporting parents in having a sense of control and normality by demonstrating empathy, and providing time and clear communication.

The role of children's hospices in perinatal palliative care and advance care planning: The results of a national British survey.

INTRODUCTION: Perinatal palliative care services are increasingly available globally, offering a range of clinical and psychological support services to families during pregnancy, in the neonatal period and following the death of a baby with a life-limiting or life-threatening condition. Little is understood about the role of children's hospice care and how it contributes to effective perinatal palliative care. DESIGN: The study aims to answer the question "what is the role of children's hospices in the provision of perinatal palliative care and advance care planning in the United Kingdom?" METHODS: An electronic survey was sent to all 54 children's hospices in the United Kingdom between May and June 2022. RESULTS: Thirty hospices responded, representing 54% of the sector. All regions of all four counties are represented. Numbers of referrals to hospices for perinatal palliative care have increased significantly over the last 5 years. Hospices provide a range of services for families and babies, usually from the point of diagnosis or recognition of a life-limiting or life-threatening condition, underpinned with counseling and emotional support. Hospices worked with a range of professionals and services, most commonly fetal medicine and neonatal services. Advance care plans were an important element of effective perinatal palliative care, strengthening parent-professional and interprofessional relationships. CONCLUSION: Children's hospice services play an important and growing role in the perinatal care of babies and families following the diagnosis or recognition of a life-limiting or life-threatening condition. The family-centered approach to care, from a broad, biopsychosocial perspective means that hospices make a unique and meaningful contribution to both the clinical and psychological needs of families. CLINICAL RELEVANCE: The family-centered approach to care, from a broad, biopsychosocial perspective means that hospices make an important contribution to both the clinical needs of babies, and psychological needs of families antenatally, in the neonatal period and after death.

A promising cognitive screener in multiple sclerosis: The NIH toolbox cognition battery concords with gold standard neuropsychological measures.

BACKGROUND: Routine cognitive screening is a priority in MS clinical care. The National Institutes of Health Toolbox (NIHTB) Cognition Battery is a 30-min instrument validated in neurological populations excluding MS. OBJECTIVES: To assess construct validity of NIHTB tests and compare classification of cognitive impairment with gold-standard tests. To evaluate relationships between fluid cognition and clinical measures. METHODS: Eighty-seven individuals, aged 30-59 years, completed the NIHTB, Minimal Assessment of Cognitive Function in MS (MACFIMS), Wechsler Adult Intelligence Scale-IV subtests, and measures of disease severity, depression, and fatigue. RESULTS: The NIHTB showed adequate convergent validity for processing speed, working memory, and episodic memory. Although fluid cognition scores from the NIHTB and MACFIMS classified a similar proportion of participants as cognitively impaired, the two batteries differed in which individuals were classified as impaired versus preserved. NIHTB fluid cognition was inversely correlated with disease severity but not related to depression or fatigue. CONCLUSIONS: The NIHTB concords with gold-standard measures, and classifies cognitive impairment at similar rates to the MACFIMS. Adjusted NIHTB fluid cognition was negatively associated with disease severity suggesting clinical utility. Psychometric validation of the NIHTB in clinical practice will elucidate its promise as a cognitive screener in MS.

Protocol for a randomized controlled trial of mindfulness-based stress reduction to improve attentional control in older adults (HealthyAgers trial).

BACKGROUND: Mindfulness meditation is a form of mind-body intervention that has increasing scientific support for its ability to reduce age-related declines in cognitive functioning, improve affective health, and strengthen the neural circuitry supporting improved cognitive and affective health. However, the majority of existent studies have been pilot investigations with small sample sizes, limited follow-up data, and a lack of attention to expectancy effects. Here, we present the study design of a Phase I/II, efficacy trial-HealthyAgers trial-that examines the benefits of a manualized mindfulness-based stress reduction program in improving attentional control and reducing mind-wandering in older adults. METHODS: One hundred fifty older adults (ages 65-85 years) will be randomized into one of two groups: an eight-week mindfulness program or an eight-week, placebo-controlled, lifestyle education program. Behavioral and neuroimaging assessments are conducted before and after the training. Participants are then invited to booster sessions once every three months for a period of 12 months with post-intervention follow-up assessments conducted at 6-months and 12-months. The primary outcomes for the study are behavioral measures of attentional control and mind-wandering. Additional, secondary outcomes include network strength in an a priori defined neuromarker of attentional control, fluid and everyday cognition, emotion regulation strategy use, and markers of inflammation. DISCUSSION: This study will establish the efficacy of a group-based, low-cost mind-body intervention for the inter-related facets of attentional control and mind-wandering in older adults. Strengths of this study include a well-designed, placebo-controlled comparison group, use of web/mobile application to track study adherence, and longitudinal follow-up. TRIAL REGISTRATION: Clinicaltrials.gov (# NCT03626532 ). Registered August 4, 2018.

Novel PGM3 compound heterozygous variants with IgE-related dermatitis, lymphopenia, without syndromic features.

BACKGROUND: Phosphoglucomutase-3 (PGM3) deficiency is a congenital disorder of glycosylation (CDG) with hyperimmunoglobulin IgE, atopy, and a variable immunological phenotype; most reported patients display dysmorphic features. The aim of the study was to characterize the genotype and phenotype of individuals with newly identified compound heterozygous variants in the phosphate-binding domain of PGM3 in order to better understand phenotypic differences between these patients and published cases. METHODS: We analyzed PGM3 protein expression, PGM3 enzymatic activity, the presence of other gene variants within the N-glycosylation pathway, and the clinical and immunological manifestations of two affected siblings. RESULTS: Patients belonged to a non-consanguineous family, presenting with atopic dermatitis, elevated levels of IgE, and CD4+ lymphopenia (a more severe phenotype was observed in Patient 2), but lacked dysmorphic features or neurocognitive impairment. Compound heterozygous PGM3 variants were identified, located in the phosphate-binding domain of the enzyme. PGM3 expression was comparable to healthy donors, but L-PHA binding in naïve-CD4+ cells was decreased. Examination of exome sequence identified the presence of one additional candidate variant of unknown significance (VUS) in the N-glycosylation pathway in Patient 2: a variant predicted to have moderate-to-high impact in ALG12. CONCLUSIONS: Our analysis revealed that L-PHA binding is reduced in naïve-CD4+ cells, which is consistent with decreased residual PGM3 enzymatic activity. Other gene variants in the N-glycosylation pathway may modify patient phenotypes in PGM3 deficiency. This study expands the clinical criteria for when PGM3 deficiency should be considered among individuals with hyper-IgE.

Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks.

Mammalian cells have evolved a common DNA damage response (DDR) that sustains cellular function, maintains genomic integrity, and suppresses malignant transformation. In pre-B cells, DNA double-strand breaks (DSBs) induced at Igκ loci by the Rag1/Rag2 (RAG) endonuclease engage this DDR to modulate transcription of genes that regulate lymphocyte-specific processes. We previously reported that RAG DSBs induced at one Igκ allele signal through the ataxia telangiectasia mutated (ATM) kinase to feedback-inhibit RAG expression and RAG cleavage of the other Igκ allele. In this article, we show that DSBs induced by ionizing radiation, etoposide, or bleomycin suppress Rag1 and Rag2 mRNA levels in primary pre-B cells, pro-B cells, and pro-T cells, indicating that inhibition of Rag1 and Rag2 expression is a prevalent DSB response among immature lymphocytes. DSBs induced in pre-B cells signal rapid transcriptional repression of Rag1 and Rag2, causing downregulation of both Rag1 and Rag2 mRNA, but only Rag1 protein. This transcriptional inhibition requires the ATM kinase and the NF-κB essential modulator protein, implicating a role for ATM-mediated activation of canonical NF-κB transcription factors. Finally, we demonstrate that DSBs induced in pre-B cells by etoposide or bleomycin inhibit recombination of Igκ loci and a chromosomally integrated substrate. Our data indicate that immature lymphocytes exploit a common DDR signaling pathway to limit DSBs at multiple genomic locations within developmental stages wherein monoallelic Ag receptor locus recombination is enforced. We discuss the implications of our findings for mechanisms that orchestrate the differentiation of monospecific lymphocytes while suppressing oncogenic Ag receptor locus translocations.

Intelligence and Neurophysiological Markers of Error Monitoring Relate to Children's Intellectual Humility.

This study explored developmental and individual differences in intellectual humility (IH) among 127 children ages 6-8. IH was operationalized as children's assessment of their knowledge and willingness to delegate scientific questions to experts. Children completed measures of IH, theory of mind, motivational framework, and intelligence, and neurophysiological measures indexing early (error-related negativity [ERN]) and later (error positivity [Pe]) error-monitoring processes related to cognitive control. Children's knowledge self-assessment correlated with question delegation, and older children showed greater IH than younger children. Greater IH was associated with higher intelligence but not with social cognition or motivational framework. ERN related to self-assessment, whereas Pe related to question delegation. Thus, children show separable epistemic and social components of IH that may differentially contribute to metacognition and learning.

The ataxia telangiectasia mutated and cyclin D3 proteins cooperate to help enforce TCRß and IgH allelic exclusion.

Coordination of V rearrangements between loci on homologous chromosomes is critical for Ig and TCR allelic exclusion. The Ataxia Telangietasia mutated (ATM) protein kinase promotes DNA repair and activates checkpoints to suppress aberrant Ig and TCR rearrangements. In response to RAG cleavage of Igκ loci, ATM inhibits RAG expression and suppresses further Vκ-to-Jκ rearrangements to enforce Igκ allelic exclusion. Because V recombination between alleles is more strictly regulated for TCRß and IgH loci, we evaluated the ability of ATM to restrict biallelic expression and V-to-DJ recombination of TCRß and IgH genes. We detected greater frequencies of lymphocytes with biallelic expression or aberrant V-to-DJ rearrangement of TCRß or IgH loci in mice lacking ATM. A preassembled DJß complex that decreases the number of TCRß rearrangements needed for a productive TCRß gene further increased frequencies of ATM-deficient cells with biallelic TCRß expression. IgH and TCRß proteins drive proliferation of prolymphocytes through cyclin D3 (Ccnd3), which also inhibits VH transcription. We show that inactivation of Ccnd3 leads to increased frequencies of lymphocytes with biallelic expression of IgH or TCRß genes. We also show that Ccnd3 inactivation cooperates with ATM deficiency to increase the frequencies of cells with biallelic TCRß or IgH expression while decreasing the frequency of ATM-deficient lymphocytes with aberrant V-to-DJ recombination. Our data demonstrate that core components of the DNA damage response and cell cycle machinery cooperate to help enforce IgH and TCRß allelic exclusion and indicate that control of V-to-DJ rearrangements between alleles is important to maintain genomic stability.

Checking nasogastric tube safety in children cared for in the community: a re-examination of the evidence base.

Nasogastric tube feeding is generally considered safe provided a nasogastric aspirate with a pH ≤5.5, which indicates that the end of tube is correctly located in the stomach, can be obtained. When this is not possible, hospital attendance or admission is usually required so that an X-ray can be undertaken to check the tube's position. This practice is based on an interpretation of the evidence that places undue importance on nasogastric aspirate pH testing before every use of a tube that is already in place, with potential negative consequences for children cared for in the community and their families. Following a re-examination of the evidence base, a revised approach is proposed in this article: when a child has a tube in place, provided its position has been confirmed as correct on initial placement using aspirate pH testing, nurses can use checks other than aspirate pH testing, alongside their clinical judgement, to determine whether it is safe and appropriate to use the tube. This proposed revised approach would reduce delayed or missed administration of fluids, feeds and medicines and enable more children to remain at home.

Anticancer peptidylarginine deiminase (PAD) inhibitors regulate the autophagy flux and the mammalian target of rapamycin complex 1 activity.

Tumor suppressor genes are frequently silenced in cancer cells by enzymes catalyzing epigenetic histone modifications. The peptidylarginine deiminase family member PAD4 (also called PADI4) is markedly overexpressed in a majority of human cancers, suggesting that PAD4 is a putative target for cancer treatment. Here, we have generated novel PAD inhibitors with low micromolar IC(50) in PAD activity and cancer cell growth inhibition. The lead compound YW3-56 alters the expression of genes controlling the cell cycle and cell death, including SESN2 that encodes an upstream inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. Guided by the gene expression profile analyses with YW3-56, we found that PAD4 functions as a corepressor of p53 to regulate SESN2 expression by histone citrullination in cancer cells. Consistent with the mTORC1 inhibition by SESN2, the phosphorylation of its substrates including p70S6 kinase (p70S6K) and 4E-BP1 was decreased. Furthermore, macroautophagy is perturbed after YW3-56 treatment in cancer cells. In a mouse xenograft model, YW3-56 demonstrates cancer growth inhibition activity with little if any detectable adverse effect to vital organs, whereas a combination of PAD4 and histone deacetylase inhibitors further decreases tumor growth. Taken together, our work found that PAD4 regulates the mTORC1 signaling pathway and that PAD inhibitors are potential anticancer reagents that activate tumor suppressor gene expression alone or in combination with histone deacetylase inhibitors.

Teaching power skills to improve physician self-efficacy, reduce burnout, and improve patient outcomes.

If doctors had a way to improve their patients' healthcare experience, improve service feedback, reduce complaints, increase treatment adherence and reduce non-attendance, while at the same time combatting burnout and compassion fatigue in clinicians and enhancing collaborative working between staff and care teams, and all for zero direct cost, could anyone argue against such an intervention? In this paper, we present the views of the educators and clinicians at Maudsley Learning that training in communication and psychological 'power skills' is not only feasible, but crucially important for physicians at all stages of training to improve both patient care and the wellbeing of clinicians themselves. We explore some of the key relevant skills and present examples of high-fidelity simulation training that demonstrate the efficacy of this modality in improving individual skills and confidence as well as inter-team and interdisciplinary working.

Using connectome-based models of working memory to predict emotion regulation in older adults.

Older adulthood is characterized by enhanced emotional well-being potentially resulting from greater reliance on adaptive emotion regulation strategies. However, not all older adults demonstrate an increase in emotional well-being and instead rely on maladaptive emotion regulation strategies. An important moderator of age-related shifts in strategy preferences is working memory (WM) and its underlying neural circuitry. As such, individual differences in the neural integrity underlying WM may predict older adults' emotion regulation strategy preferences. Our study used whole-brain WM networks-derived from young adults using connectome-based predictive modeling-to predict WM performance and acceptance strategy use in healthy older adults. Older adults (N = 110) completed baseline assessments as part of a randomized controlled trial examining the impact of mind-body interventions on healthy aging. Our results revealed that the WM networks predicted WM accuracy but not acceptance use or difficulties in emotion regulation in older adults. Individual differences in WM performance, but not WM networks, moderated relationships between image intensity and acceptance use. These findings highlight that robust neural markers of WM generalize to an independent sample of healthy older adults but may not generalize beyond cognitive domains to predict emotion-based behaviors.

Trait mindfulness and emotion regulation responsiveness to negative affect in daily life.

Objectives: Recent conceptualizations of adaptive emotion regulation is predicated on the ability to flexibly use emotion regulation strategies to meet changing contextual demands. Although trait mindfulness has been linked to enhanced emotional well-being and use of adaptive emotion regulation strategies, there is a dearth of literature examining associations between trait mindfulness and emotion regulation flexibility. Further, despite a rich literature suggesting that emotion regulation processes change with age, no study to date has assessed whether the role of trait mindfulness on emotion regulation responsiveness to negative emotions-a component of emotion regulation flexibility-differs between young and older adults. Methods: The current study recruited 130 young adults and 130 older adults to assess trait mindfulness, emotion regulation strategy use, and emotion regulation responsiveness of six distinct strategies in daily life. Results: Across the full sample, trait mindfulness was related to reduced distraction (ß = -0.11, t(238.09) = -3.02, p = .003) and expressive suppression (ß = -0.15, t(237.70) = -4.62, p < .001) strategy use. Age moderation analyses revealed that trait mindfulness was associated with reduced expressive suppression responsiveness (ß = 0.12, t(247) = 2.31, p = .022) in young adults and increased detached reappraisal responsiveness among older adults (ß = 0.15, t(247) = -2.95, p = .003). Conclusions: The current findings highlight the importance of understanding how trait mindfulness is associated with strategy use and responsiveness to negative affect changes in daily life as well as how these patterns may shift across the lifespan. Manuscript Pre-registration: Open Science Framework, registration number: z5g8v.

Impact of mindfulness training on emotion regulation in multiple sclerosis: Secondary analysis of a pilot randomized controlled trial.

Purpose/Objective Research: This secondary analysis of a pilot randomized controlled trial in people with multiple sclerosis (PwMS) aimed to compare mindfulness-based training (MBT), adaptive cognitive training (aCT), and a waitlist control (WL) on the use of emotion regulation strategies during daily worries and ruminations. Further, we examined cognitive functioning as a moderator of training effects. RESEARCH METHOD/DESIGN: Sixty-one PwMS were randomized into an MBT, aCT, or a WL control group for four weeks. Participants completed daily diaries assessing their use of emotion regulation strategies and measures of cognitive functioning at pre- and posttraining. The frequency of acceptance use, maladaptive strategies, and cognitive reappraisal, as well as the success of acceptance use, were the primary outcomes of interest. We also examined whether a cognitive composite score moderated treatment gains. RESULTS: Relative to pretraining, at posttraining, participants in the MBT group used acceptance more frequently, and this change was significantly greater compared to the change in aCT and WL groups. Training did not have differential effects on the frequency of maladaptive strategy and cognitive reappraisal use or on the success of acceptance use. Cognitive functioning did not moderate observed treatment gains. CONCLUSION/IMPLICATIONS: Our findings, based on this pilot study, suggest that after brief training in mindfulness meditation, PwMS used more acceptance strategies to regulate their emotions. Future studies with larger sample sizes, longer duration of treatment, and longitudinal follow-up are needed to better understand the efficacy of mindfulness mediation for promoting affective and cognitive health in PwMS. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

TRACking health behaviors in people with Multiple Sclerosis (TRAC-MS): Study protocol and description of the study sample.

Introduction: People with multiple sclerosis (PwMS) experience a range of physical, cognitive, and affective symptoms. Behavioral interventions targeting increased physical activity show promising support as low-cost methods to improve working memory, episodic memory, and processing speed in PwMS. In this randomized controlled trial, we will examine the efficacy of a pedometer-tracking intervention, designed to increase low-to-moderate levels of physical activity, for improving working memory in PwMS. Methods and Analysis: Eighty-seven PwMS, between the ages of 30-59, have been recruited for the study. Seventy-five of the eligible and interested individuals were randomized to six-month health behavior monitoring groups: a Step-track group or a Water-track group (serving as the active control). Neuropsychological measures, assessing the primary outcome of the study, were administered at pre, midpoint, and post-intervention. Exploratory factor analysis of neuropsychological measures resulted in three factors: a working memory/processing speed factor, a visual episodic memory factor, and a verbal episodic memory factor. Changes in this latent measure of working memory/processing speed is the primary outcome of the current study. Functional MRI data will be analyzed to examine changes in the functional connectivity of the neural network supporting working memory. Ethics and dissemination: The institutional review board granted approval for the study and all participants provided written informed consent. The results of this study will provide support showing that step-tracking increases overall levels of physical activity, improves working memory and processing speed, and strengthens the neural circuitry that supports better cognition. Evidence from this study will thus offer promising support for the routine use of step-tracking devices to improve cognitive functioning in PwMS. Study results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

Rhamnan sulfate reduces atherosclerotic plaque formation and vascular inflammation.

OBJECTIVE: While lipid-lowering drugs have become a mainstay of clinical therapy these treatments only slow the progression of the disease and can have side effects. Thus, new treatment options are needed to supplement the effects of lipid lowering therapy for treating atherosclerosis. We examined the use of an inexpensive and widely available marine polysaccharide rhamnan sulfate as an oral therapeutic for limiting vascular inflammation and atherosclerosis. METHODS AND RESULTS: We found rhamnan sulfate enhanced the barrier function of endothelial cells, preventing the deposition of LDL and maintaining barrier function even in the presence of glycocalyx-degrading enzymes. Rhamnan sulfate was also found to bind directly to FGF-2, PDGF-BB and NF-κB subunits with high affinity. In addition, rhamnan sulfate was a potent inhibitor of NF-κB pathway activation in endothelial cells by TNF-α. We treated ApoE-/- mice with a high fat diet for 4 weeks and then an addition 9 weeks of high fat diet with or without rhamnan sulfate. Rhamnan sulfate reduced vascular inflammation and atherosclerosis in both sexes of ApoE-/- mice but had a stronger therapeutic effect in female mice. Oral consumption of rhamnan sulfate induced a significant decrease in cholesterol plasma levels in female mice but not in male mice. In addition, there was a marked reduction in inflammation for female mice in the liver and aortic root in comparison to male mice. CONCLUSIONS: Rhamnan sulfate has beneficial effects in reducing inflammation, binding growth factors and NF-κB, enhancing endothelial barrier function and reducing atherosclerotic plaque formation in ApoE-/- mice.