Long-term effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia: an observational case series.

BACKGROUND: We assessed long-term real-world effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia (HoFH). METHODS: Retrospective case series of six patients with HoFH treated with lomitapide in an Italian clinic. Changes in low-density lipoprotein cholesterol (LDL-C) during lomitapide treatment were assessed. The effect on LDL-C of PCSK9 inhibitors, apheresis and lomitapide was evaluated. Additionally, high-density lipoprotein cholesterol (HDL-C), gastrointestinal tolerability, hepatic steatosis/elasticity, transaminases, and cardiovascular events and symptoms were assessed. RESULTS: Median age at HoFH clinical and molecular diagnoses was 25 (range 2-49) and 40 (29-71) years, respectively. Five (83.3%) had prior cardiovascular events. One patient received apheresis, which was subsequently discontinued. All patients received PCSK9 inhibitors but discontinued due to minimal effectiveness. Median (range) age at lomitapide initiation was 44 (28-73) years, with a median 47 (18-85) months' treatment (mean dose 17.5 [5-40] mg/day). Mean (SD) baseline LDL-C was 263.2 (148.1) mg/dL, which decreased by 80% at nadir (52.8 [19.2] mg/dL) and 69% at last follow-up (81.3 [30.5] mg/dL). Four patients (66.7%) achieved LDL-C < 70 mg/dL sometime during follow-up, all of whom also achieved LDL-C < 55 mg/dL. Adverse events (AEs) were generally mild to moderate, hepatic steatosis was either absent or mild/moderate and hepatic elasticity remained normal in all but two patients (> 70 years old). All patients with reported cardiovascular symptoms had improvements in symptoms, and all patients reported stabilization or regression of intima-media thickness and atheromatous plaques. CONCLUSIONS: These long-term, real-world data demonstrate that lomitapide substantially reduced LDL-C for up to seven years. Most patients achieved LDL-C goal at some point, consistent with published Phase III trial and real-world evidence data. No patient discontinued lomitapide treatment. Further long-term follow-up in a larger patient population will be important to determine cardiovascular and other outcomes.

Mobilizing or Sedative Effects? A Narrative Review of the Association Between Intergroup Contact and Collective Action Among Advantaged and Disadvantaged Groups.

ACADEMIC ABSTRACT: In this narrative review, we examined 134 studies of the relationship between intergroup contact and collective action benefiting disadvantaged groups. We aimed to identify whether, when, and why contact has mobilizing effects (promoting collective action) or sedative effects (inhibiting collective action). For both moderators and mediators, factors associated with the intergroup situation (compared with those associated with the out-group or the in-group) emerged as the most important. Group status had important effects. For members of socially advantaged groups (examined in 98 studies, 100 samples), contact had a general mobilizing effect, which was stronger when contact increased awareness of experiences of injustice among members of disadvantaged groups. For members of disadvantaged groups (examined in 49 studies, 58 samples), contact had mixed effects. Contact that increased awareness of injustice mobilized collection action; contact that made the legitimacy of group hierarchy or threat of retaliation more salient produced sedative effects. PUBLIC ABSTRACT: We present a review of existing studies that have investigated the relationship between intergroup contact and collective action aimed at promoting equity for disadvantaged groups. We further consider the influence of contact that is positive or negative and face-to-face or indirect (e.g., through mass or social media), and we distinguish between collective action that involves socially acceptable behaviors or is destructive and violent. We identified 134 studies, considering both advantaged (100 samples) and disadvantaged groups (58 samples). We found that intergroup contact impacts collective action differently depending on group status. Contact generally leads advantaged groups to mobilize in favor of disadvantaged groups. However, contact has variable effects on members of disadvantaged groups: It sometimes promotes their collective action in support of their own group; in other cases, it leads them to be less likely to engage in such action. We examine when and why contact can have these different effects.

Cardiovascular risk in rare diseases: a prognostic stratification model in a cohort of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ; as other chronic diseases, it leads to increased risk of atherosclerosis and cardiovascular (CV) disease. The aim of our observational study was to define a prognostic stratification model of sarcoidosis patients based on the evaluation of CV risk through common carotid Doppler ultrasound and cardiovascular risk scores assessment; for this reason, a clinical phenotyping of sarcoidosis patients in four subgroups was done, based on the different organ involvement. A cohort of 53 sarcoidosis patients and a cohort of 48 healthy volunteers were enrolled. Results showed that CV risk was higher in sarcoidosis cohort than in the control group when evaluated through CV risk scores and Doppler parameters: peak-systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly lower in sarcoidosis cohort (p = 0.045 and p = 0.017, respectively), whereas intima media thickness (IMT) showed higher values in sarcoidosis group than in controls (p = 0.016). The analysis of sarcoidosis phenotypes showed no significative differences of CV risk among them when CV risk scores were considered, while partial differences emerged by evaluating subclinical atherosclerosis. Results also highlighted a relationship between CV risk score and carotid Doppler ultrasound parameters: EDV showed an inverse correlation with Framingham score (R = - 0.275, p = 0.004), whereas IMT showed a direct one (R = 0.429; p = 0.001); furthermore, an inverse correlation between PSV and EDV and illness duration (R = - 0.298, p = 0.030 and R = - 0.406, p = 0.002, respectively) was found, so suggesting a higher CV risk in patients with a longer story of disease.

Why Might Women Justify Dating Violence? The Role of Men's Sexual Objectification of Their Romantic Partners Within Heterosexual Relationships.

Men's partner-sexual objectification has been linked to increased self-objectification and diminished well-being in women. Some recent findings have also demonstrated that men's partner-sexual objectification is related to increased violence in the relationship. However, mechanisms driving this association remain unexplored. In the present research, we collected data on women and men involved in heterosexual romantic relationships and investigated the associations between men's partner-sexual objectification, women's self-objectification, and both partners' attitudes toward dating violence. Study 1 (N = 171 heterosexual couples) provided first evidence for the link between men's partner-sexual objectification and their attitudes toward dating violence. Furthermore, men's attitudes toward dating violence mediated the relationship between sexual objectification of their partners and women's attitudes toward dating violence. These results were replicated in Study 2 (N = 235 heterosexual couples). Findings of this study also revealed that, along with men's attitudes toward dating violence, women's self-objectification acted as a mediating mechanism linking experiences of being sexually objectified by the romantic partner and attitudes toward dating violence in women. Implications of our findings for the issue of dating violence are discussed.

Managing the unexpected: Bicultural identity integration during the COVID-19 emergency.

Unexpected and sudden emergency situations such as COVID-19 may render ethnic minorities particularly vulnerable to experiencing negative outcomes. Yet, we put forward that Bicultural Identity Integration (BII) - the degree to which bicultural individuals perceive their cultural identities as compatible and overlapping - may represent a resource in times of emergencies, since it may positively influence, through enhancement of psychological well-being, how bicultural individuals respond in terms of distress and coping strategies. Based on this assumption, the present study aimed at examining the relationship between BII and responses to COVID-19. N = 370 bicultural individuals (mean age = 26.83, SD = 8.74) from different cultural backgrounds were recruited online and completed measures of BII, psychological well-being, COVID-19 distress and coping strategies (positive attitudes, avoidance, social support seeking) during the second wave of the COVID-19 pandemic in Italy. We tested a model in which BII was the predictor, psychological well-being was the mediator and reactions to the COVID-19 emergency (distress, use of coping) were the outcomes. This model was tested against two alternative models. The proposed model showed a better fit to the data compared to the alternative models. In this model, psychological well-being mediated the relationship between BII (harmony) and coping strategies, except social support seeking. These findings highlight the important role played by BII in emergency situations, as it may indirectly, through enhancement of psychological well-being, contribute to enhance biculturals' adaptive reactions in terms of distress as well as affect coping strategies during highly stressful events.

Effects of intergroup contact on explicit and implicit outgroup attitudes: A longitudinal field study with majority and minority group members.

A longitudinal field study tested the long-term effects (three years) of intergroup contact on both explicit and implicit outgroup attitudes. Participants were majority (Italian) and minority (immigrant) high-school students, who were tested at four waves from the beginning of their first year in high-school to the end of the third school year. Results revealed, first, a longitudinal association of quantity (but not quality) of contact with lower intergroup anxiety and more positive explicit attitudes, as well as bidirectional effects over time between explicit attitudes and intergroup anxiety, on the one hand, and quantity and quality of contact, on the other. Second, reduced intergroup anxiety mediated the association between quantity of contact and improved explicit attitudes over time. Third, the product of quantity and quality of contact longitudinally predicted more positive implicit outgroup attitudes over school years. We discuss the theoretical and practical implications of findings.

I love you too much to keep social distance: Closeness in relationships and (dis)engagement in preventive behaviors during the COVID-19 pandemic.

Although we are witnessing a new phase in the management of COVID-19, understanding what predicts adherence to preventive behaviors still remains crucial. In this study we focus on interpersonal relationships by specifically investigating whether engagement in preventive behaviors when in the presence of others may be a function of the type of relationship (in terms of closeness) one has with others. Because close others are often perceived similar to the self compared to strangers, we put forward that close relationships may inadvertently decrease COVID-19 risk perceptions which may ultimately decrease compliance with recommended behaviors when in their presence. To test this hypothesis, 747 Italian respondents were invited to answer one out of four versions of a questionnaire differing on the target (i.e., friends vs. parents vs. grandparents vs. strangers), including questions regarding COVID-19 risk perceptions and intentions to engage in preventive behaviors. Mediation analysis showed that close relationships (i.e., with friends, parents, and grandparents) compared to nonclose relationships (i.e., with strangers) predicted lower intentions to engage in preventive behaviors via lower risk perceptions. Altogether, these results shed light on the role played by closeness in indirectly shaping individuals' dis(engagement) in preventive behaviors and contribute to better understand possible unconscious biases which may undermine our safety during the COVID-19 pandemic.

At the core of cyberaggression: A group-based explanation.

In this study, prototypicality of the aggressor was tested as a group-level factor predicting social media users' active participation in cyberaggression. Participants were exposed to a fictitious conversation, in which either a prototypical versus non-prototypical user posted an aggressive comment as a reply to a provocative comment. In line with self-categorization theory, we hypothesized that bystander participants would post an aggressive comment and rate the aggression as acceptable to a greater extent in the prototypical than in the non-prototypical condition. Furthermore, we predicted that perceived normativity of aggression would mediate the effect of prototypicality. Results supported these predictions and showed that prototypical members affect the extent to which collective aggressive behaviors in online interactions are approved and enacted. These findings highlight the importance of group-level factors in the study of cyberaggression and provide important information for understanding the psychological underpinnings of collective forms of online aggression.

Comparing story reading and video watching as two distinct forms of vicarious contact: An experimental intervention among elementary school children.

Research has shown that vicarious contact, that is observing an interaction between ingroup and outgroup members, can improve intergroup relations. Although vicarious contact has been operationalized in different ways, mainly via story reading or video watching, an experimental comparison of these different strategies is still missing. We conducted a school intervention with the aim of comparing the two most used forms of vicarious contact, namely story reading and video watching. Elementary schoolchildren without disabilities (N = 292) were assigned to one of three different conditions: reading a story; watching a video; control. In the two vicarious contact conditions, participants read or watched the story of a child with disability becoming friends with children without disabilities; in the control condition, participants only completed the dependent measures. Results revealed that, in general, both vicarious contact conditions were equally effective in improving outgroup attitudes and behavioural intentions. In addition, they operated with the same strength through the same underlying processes (IOS, ingroup norms). We discuss theoretical and practical implications in the context of vicarious contact as a prejudice-reduction intervention.

Reducing prejudice toward Syrian refugee children: A vicarious contact intervention among Turkish elementary school children.

We conducted an experimental intervention to test the effectiveness of vicarious contact in the relationship between Turkish and Syrian elementary school children; the participants were Turkish children. We used a mixed-methods approach, investigating effects by using both quantitative and qualitative methodologies. Participants in the experimental condition were asked to read stories on positive contact between Turkish and Syrian children over the course of six weekly sessions. The results revealed that vicarious contact, compared to a control condition where participants did not engage in any activity, led to greater intentions to help outgroup members. Importantly, effects only emerged among children who reported higher initial negative outgroup attitudes. Results from qualitative data revealed that vicarious contact produced richer, more positive, and complex representations of the relationships and friendships between groups. We discuss the theoretical and practical implications of these findings.

Correction: Truth and lies in your eyes: Pupil dilation of White participants in truthful and deceptive responses to White and Black partners.

[This corrects the article DOI: 10.1371/journal.pone.0239512.].

Truth and lies in your eyes: Pupil dilation of White participants in truthful and deceptive responses to White and Black partners.

In the present study, we examined the pupillary response of White participants who were asked to tell the truth or lie to White or Black partners. Research on cues to deception has assumed that lying is more cognitively demanding that truth telling. In line with this assumption, previous studies have shown that lying is associated with greater pupil dilation, a behavioral cue that typically manifests itself under conditions of stress or cognitive effort. In accordance with these results, we predicted greater pupil dilation when lying than when telling the truth. Furthermore, pupil dilation was expected to be greater when responding to White than Black partners. Finally, we hypothesized that pupil dilation would be greater when lying to White than Black partners. Participants were instructed to answer a set of questions, half truthfully and half deceptively. They were led to believe that White vs. Black partners (one male and one female) would ask the questions via computer connection. Indeed, we used feminine and masculine synthetic voices. Pupil dilation was assessed with a remote eye-tracking system. Results provided support for the first two hypotheses. However, the predicted interaction between race of partners and truth status of message (lying vs. telling the truth) was nonsignificant. Our findings highlight the importance of considering race in the study of truthful and deceptive communications.

Intergroup fears and concerns among minority and majority groups: Implications for contact and attitudes.

AIMS: Driven by the literature on pluralistic ignorance, our research investigates fear of appearing racist, being rejected, discriminated, and disinterest in intergroup contact as antecedents of contact and outgroup attitudes, focusing on attributional differences between the majority and minority group perspectives. METHODS: Questionnaires were distributed in schools in Northern Italy. Participants were 400 Italian and 141 immigrant high-school students. RESULTS: The results showed that the lack of interest in contact was the strongest predictor of contact for the majority group. For the minority group, fear of rejection emerged as the strongest predictor. The majority group attributed the minority to avoid contact most strongly due to the fear that they would be rejected, and the minority group perceived it was due to the majority not being interested in contact. CONCLUSION: Our research contributes to understanding the divergent concerns the majority and minority groups have in relation to intergroup contact and discusses the importance of tackling these concerns.