Alzheimer's disease (AD) alters astrocytes, but the effect of Aß and Tau pathology is poorly understood. TRAP-seq translatome analysis of astrocytes in APP/PS1 ß-amyloidopathy and MAPT
tauopathy mice ...revealed that only Aß influenced expression of AD risk genes, but both pathologies precociously induced age-dependent changes, and had distinct but overlapping signatures found in human post-mortem AD astrocytes. Both Aß and Tau pathology induced an astrocyte signature involving repression of bioenergetic and translation machinery, and induction of inflammation pathways plus protein degradation/proteostasis genes, the latter enriched in targets of inflammatory mediator Spi1 and stress-activated cytoprotective Nrf2. Astrocyte-specific Nrf2 expression induced a reactive phenotype which recapitulated elements of this proteostasis signature, reduced Aß deposition and phospho-tau accumulation in their respective models, and rescued brain-wide transcriptional deregulation, cellular pathology, neurodegeneration and behavioural/cognitive deficits. Thus, Aß and Tau induce overlapping astrocyte profiles associated with both deleterious and adaptive-protective signals, the latter of which can slow patho-progression.
This study explored whether individual differences in self-reported emotional flooding were associated with observational behaviors and experienced and displayed anger during a 10-min problem solving ...discussion. A sample of 233 married or cohabiting couples, comprising 4 groups (distressed with intimate partner violence IPV, distressed/nonIPV, satisfied/IPV, and satisfied/nonIPV) was recruited via random digit dialing. Consistent with predictions, both men's and women's flooding were positively associated with partners' negative affect variables, including partners' experienced and displayed anger, as well as positively associated with their own anger. A multinomial logistic regression revealed significant differences between flooding in prediction of couples' group status; specifically that higher levels of emotional flooding were reported by distressed and IPV couples compared with other types of couples. Finally, couples that included at least 1 member high on self-reported emotional flooding were less effective in solving problems during the conflict discussion. Implications and future directions are discussed.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
In this study, the authors assessed men's and women's partner and parent physical aggression among 453 representatively sampled families with young children. The prevalences of partner aggression and ...of severe parent aggression were higher than previously reported. Substantial rates of co-occurrence were found. Risk ratios and regression analyses indicated that connections between (a) husbands' and wives' partner aggression and (b) mothers' and fathers' parent aggression were especially strong. Patterns of co-occurrence pointed to the probable relative importance of family-level, in comparison with individual, predictors of aggression. Patterns of co-occurring violence are described in light of the theoretical literature. Implications for studying family violence in community samples are discussed.
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In the present investigation, we studied the development of 6 physically aggressive behaviors in infancy and toddlerhood, posing 3 questions (a) How do the prevalences of individual physically ...aggressive behaviors change from 8, 15, and 24 months? (b) Are there groups of children who show distinctive patterns in the way individual physically aggressive behaviors develop over time? (c) What are the behavioral pathways leading from 8- to 24-month acts of physical aggression? Mothers and fathers (N = 272) from a moderately at-risk population reported on their children's physical aggression at each time point. The results revealed the commonality of physical aggression at all ages studied and the diverging developmental patterns of individual behaviors. Some physically aggressive behaviors became less common (e.g., hair pulling), while others became more common (e.g., hitting), with age. Roughly 42% of the children exhibited an increased propensity, relative to their peers, to aggress at all ages. Kicking, biting, hair pulling, and pinching/scratching at 8 months were the first steps on behavioral pathways leading to physical aggression at 24 months. These pathways principally suggested heterotypic continuity in physical aggression.
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Given its critical role in T-cell signaling, interleukin-2–inducible kinase (ITK) is an appealing therapeutic target that can contribute to the pathogenesis of certain infectious, autoimmune, and ...neoplastic diseases. Ablation of ITK subverts Th2 immunity, thereby potentiating Th1-based immune responses. While small-molecule ITK inhibitors have been identified, none have demonstrated clinical utility. Ibrutinib is a confirmed irreversible inhibitor of Bruton tyrosine kinase (BTK) with outstanding clinical activity and tolerability in B-cell malignancies. Significant homology between BTK and ITK alongside in silico docking studies support ibrutinib as an immunomodulatory inhibitor of both ITK and BTK. Our comprehensive molecular and phenotypic analysis confirms ITK as an irreversible T-cell target of ibrutinib. Using ibrutinib clinical trial samples along with well-characterized neoplastic (chronic lymphocytic leukemia), parasitic infection (Leishmania major), and infectious disease (Listeria monocytogenes) models, we establish ibrutinib as a clinically relevant and physiologically potent ITK inhibitor with broad therapeutic utility. This trial was registered at www.clinicaltrials.gov as #NCT01105247 and #NCT01217749.
•Ibrutinib is the first clinically viable irreversible ITK inhibitor.•Ibrutinib inhibits the formation of Th2 but not Th1 immunity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Commonly used scales of psychological intimate partner violence (ψIPV) for adolescents may not include sufficient items to measure adequately different forms of ψ aggressive behaviors. They may also ...characterize as harmful ψ aggressive behaviors occurring in non-conflictual or joking contexts. The current study examined a new scale, the Relationship Behavior Survey (RBS), which was designed to measure three different forms of ψIPV (denigrating, controlling, and intrusive behaviors) and the appraisals of the perpetrator’s intent. Factor structure was examined, and incremental validity was tested by examining the relation of the RBS to general aggressive tendencies and physical IPV after accounting for the emotional abuse and threatening behavior subscales of the Conflict in Adolescent Dating Relationships Inventory (CADRI). Criterion validity and gender differences were also examined. Data were collected using an online survey from a national sample of 1,100 13 to 17-year-olds in the United States (51% identified as female, 80% as White) in a dating relationship. Confirmatory factor analysis supported one ψIPV construct for males and females. The RBS demonstrated incremental validity; criterion validity was supported for controlling intent for males and females and mistrust intent for females. Joking intent was the most reported intent for males and correlated unexpectedly with physical IPV. The RBS captures a larger range of ψIPV behaviors than the CADRI. The addition of intent appraisals provides important information to differentiate forms of ψIPV, particularly in relation to acts motivated by coercion and mistrust.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK, VSZLJ
Parental help-seeking preferences may help explain the treatment gap in child mental health. This study examined mothers' and fathers' help-seeking behaviors for child mental health to further ...understand their individual preferences for treatment. A total of 394 mothers and fathers completed questionnaires assessing the types of help sought for mental health concerns for a target child (age 3-7 years), as well as measures representing illness profile, predisposing characteristics, and barriers/facilitators proposed to influence help-seeking. Parents often sought informal rather than professional help. Regression modelling indicated mothers' different help-seeking behaviors were significantly associated with illness profile (marital quality, child mental health, parental education), predisposing factors (parental attributions, child age), and family income, while fathers' different help-seeking behaviors were significantly associated with child demographics (age, gender). The results support expanding treatments into nonclinical settings and improving child mental health literacy to improve appropriate parental help-seeking for child mental health concerns.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Two studies examined the impact of the implementation of the Field-tested Assessment, Intervention-planning, and Response (FAIR) system, a system-level intervention for determining whether ...allegations of family maltreatment meet threshold for abuse or neglect, on alleged recidivism. Data were collected at the 10 U.S. Army installations with the largest family maltreatment caseloads. Participants were family members who had an allegation of family maltreatment (i.e., child maltreatment or partner abuse) during one of the two study periods. Data were collected when Family Advocacy Program staff used the then-in-place system (Case Review Committee) and later the FAIR system. In Study 1, cases were followed for 6 months following the initial maltreatment allegation to measure the occurrence of subsequent allegations of any type. Additionally, at five installations, alleged victims of partner abuse were recruited into a study (Study 2) in which they anonymously reported on intimate partner violence via telephone. In Study 1, the advantage for the FAIR condition was concentrated in cases with unsubstantiated initial determinations; the mean relative risk reduction for recidivism was 0.48. In Study 2, FAIR extended median time to recidivism by approximately 170%. These results replicate and extend earlier findings that employing the FAIR system can result in decreased family maltreatment re-offense.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK, VSZLJ
To inform interpersonal models of intimate partner violence (IPV), the present study examines patterns of vocally encoded emotional arousal during the conversations of mixed-gender couples who ...reported on the extent of physical and psychological IPV and degree of relationship satisfaction (N = 149). All couples completed two problem-solving discussions. Emotional arousal was measured continuously during each conversation using vocal fundamental frequency. Contrary to expectations, results demonstrated that trajectories of arousal differed based on gender, IPV, and relationship satisfaction. Within conversations, men demonstrated linear increases in arousal at higher levels of IPV, suggesting that men may either struggle to contain their emotions or use heightened emotional expression as a conflict strategy in relationships with more extensive IPV. Conversely, women exhibited different trajectories of arousal depending on the combinations of relationship satisfaction and couple IPV, except at higher levels of their own satisfaction. Specifically, when women reported being highly satisfied in their relationships, they demonstrated similarly shaped trajectories across all levels of IPV and men's satisfaction. Together, this suggests that women's higher relationship satisfaction may buffer their emotional expression, although this may not always be adaptive within the context of relationships with extensive IPV. Overall, this study offers insight into the dynamic interpersonal processes linked with relationship distress and IPV and implies the need for a more nuanced, interpersonal research agenda for IPV research.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
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