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The evaluation and management of patients who sustain recurrent thromboembolic events while taking therapeutic anticoagulation have not been well characterized; moreover, there has been no systematic review or randomized trial focused on treating patients with recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) during anticoagulant treatment. Therefore, we developed a pilot trial to compare rivaroxaban plus aspirin versus acenocoumarol in patients with recurrent venous thromboembolism despite ongoing anticoagulation with rivaroxaban.The study was a multicenter, randomized clinical trial. We randomly assigned patients with objectively documented recurrent venous thromboembolism to receive rivaroxaban (20 mg once a day) plus aspirin (300 mg once a day) or an adjusted dose of acenocoumarol. The study was designed to evaluate the incidence of recurrent thromboembolic events (recurrent ipsilateral or contralateral DVT, PE, ischemic stroke, and myocardial infarction) and hemorrhagic events.A total of 58 patients were randomized: 28 were allocated to the rivaroxaban plus aspirin group and 30 to the acenocoumarol group. After 90 days of follow-up, three recurrent thromboembolic events (primary outcome) occurred in the acenocoumarol group - two DVTs and one ischemic stroke - and zero events in the rivaroxaban plus aspirin group (risk ratio [RR] 0.15; 95 % confidence interval [CI] 0.008-2.83; P = 0.20). Minor bleeding occurred in five patients in the acenocoumarol group and zero in the rivaroxaban plus aspirin group (RR 0.09; 95 % CI 0.005-1.68; p = 0.10). There was one non-fatal gastrointestinal major bleed in the rivaroxaban plus aspirin group.In this pilot study, there were no significant differences in any outcome assessed; however, recurrent thromboembolic events and minor bleeding events occurred numerically less frequently in the rivaroxaban plus aspirin group. These data suggest the need to carry out more extensive randomized studies with sufficient statistical power to clarify these results.

Introduction: There is a high incidence of venous thromboembolism (VTE) in patients with Multiple Myeloma (MM), however; until now, the exact mechanisms behind VTE in MM are unknown, and some of the elements that may play a significant role are the treatment with an immunomodulator (IMiD) and acquired resistance to activated protein C (APC). Objective: The study aims to reveal the possible mechanisms linked to the reduced antithrombotic activity of APC associated with thalidomide. Methods: The molecular docking approach was used to ascertain the in silico inhibitory potential of thalidomide on the APC protease domain in the architecture of the catalytic triad and its interaction with major substrate binding sites. Results: The coupling showed that the inhibitory activity of thalidomide depends on the induction of structural changes in the protease domain of APC, at the level of the Ser/His/Asp catalytic triad, as a result of a significant increase between the distances of CαAsp102 and Cα Ser195 (11.175 angstroms, increase 14.83%) and between CαSer195 and CαHis57 (9.478 angstroms, increase 13.78 %). This can result in an inefficient transfer of the proton between these residues, the other possible mechanism of inhibition, is a potential reduced binding of the substrate as a result of a direct interaction through a carbon-hydrogen bond on His57, an H-bond on Arg306, and a carbon hydrogen bond on Arg506. Conclusion: We demonstrate the in silico inhibitory potential of thalidomide on APC, through two possible inhibition mechanisms, a pathophysiologically relevant finding to understand the factors that can affect the stability and functions of APC in vivo.

Supplemental Material, sj-pdf-1-spr-10.1177_02654075211034566 for Connecting with others: Dispositional and situational relatedness during the college transition by Jordan A. Booker, Erika Hernandez, Karen E. Talley and Julie C. Dunsmore in Journal of Social and Personal Relationships

Emotion socialization is defined as how socializers teach children about emotions, and one way socializers do this is through reminiscing about past emotional events. In the current study, I build on prior research on maternal emotion socialization by examining grandmothers' role in socializing children's emotions, given the prominence of grandparents' involvement in caregiving tasks for minority and underrepresented families. I also incorporate indirectness, a concept that is well-established in linguistic research. Rather than focusing on what family members say during emotion-related reminiscing, indirectness assesses how family members communicate reminiscing content. Participants for Study 1 – the Family Interaction Study – were 18 grandmother-mother-child triads (5 Latinx and 13 Appalachian) with children in the 3rd, 4th, or 5th grade. Families discussed two past, shared emotional events together, one positive event and one negative, in both triadic and dyadic interactions. Grandmothers', mothers', and children's speech was coded for use of emotion labels and explanations, using an established coding scheme in the emotion socialization literature, as well as for indirectness, using a coding scheme created in my previous work. Grandmothers and mothers completed questionnaires about children's social outcomes (emotion regulation and social competence), and children self-reported on their own social behavior. Grandmothers and mothers also completed questionnaires about their beliefs about children's emotions, as well as their experiences related to being underrepresented. Finally, grandmothers and mothers responded to an open-ended prompt about their race, ethnicity, and culture in relation to emotion and family values. Descriptive analyses for the Family Interaction Study were conducted to examine similarities and differences between grandmothers' and mothers' speech during familial conversations. Descriptive results indicate that grandmothers and mothers were involved during reminiscing conversations to a similar extent. Given the small sample size for this study, I was not able to conduct the planned within- and across-group tests for associations between grandmothers' and mothers' experiences and beliefs, their emotion-related discourse, and children's social outcomes. Grandmothers' and mothers' responses to the open-ended prompt were analyzed with a thematic analysis. Qualitative results identified themes present in existing literature, such as those regarding emotion expression, emotion regulation, and teaching of emotion, as well as themes not yet identified in the literature, such as the role of religion in the socialization of children's emotions. Participants for Study 2 – the Online Grandmothers Study – were 150 grandmothers (52 African American, 51 Latinx, and 50 Appalachian) with grandchildren in the 3rd, 4th, or 5th grade. Grandmothers completed the same questionnaires as the participants in the Family Interaction Study about grandchildren's social outcomes, as well as their beliefs about children's emotions, and their experiences related to being underrepresented. Quantitative analyses for this study were conducted to investigate associations between grandmothers' social position, beliefs about emotion, and grandchildren's social outcomes. Results for the Online Grandmothers Study indicate links between grandmothers' value of positive emotion and children's lower lability/negativity, lower internalizing behaviors, and lower externalizing behaviors, particularly for African American families. Further, for Appalachian families, results indicate a link between grandmothers' belief in parental guidance of children's emotions and children's lower externalizing behaviors. Thus, results suggest that grandmothers play a unique role in children's socio-emotional development, one that is both similar and different to the mother's. This role may pertinent for development in middle childhood for a few reasons, including grandmothers' influence on children's developing sense of self, promoting children's positive coping as they transition into adolescence, as well as providing salient experiences regarding race/ethnicity that may serve as a basis for racial-ethnic identity (REI) development. Overall, findings highlight the importance of considering intergenerational shared caregiving in minority families and the roles of grandmothers as socializing agents. Doctor of Philosophy Grandmothers are important for family functioning and influence how children develop social skills. In the current studies, I examined grandmothers' emotion talk, beliefs about emotions, and experiences as underrepresented, as well as links to children's social skills. Participants for Study 1 – the Family Interaction Study – were 18 grandmother-mother-child triads (5 Latinx and 13 Appalachian) with children in the 3rd, 4th, or 5th grade. Families discussed past events together and speech was coded for emotion talk. Grandmothers and mothers completed questionnaires about their beliefs about children's emotions, children's social outcomes, as well as their experiences as being underrepresented. Finally, grandmothers and mothers responded to an open-ended prompt about their race, ethnicity, and culture in relation to emotion and family values. Descriptive results indicate that grandmothers were involved during reminiscing conversations to a similar extent as mothers. Themes were identified in grandmothers' and mothers' conversations about the open-ended prompt. Notably, grandmothers and mothers identified religion as an important influence on emotion in their families. Participants for Study 2 – the Online Grandmothers Study – were 150 grandmothers (52 African American, 51 Latinx, and 50 Appalachian) with grandchildren in the 3rd, 4th, or 5th grade. Grandmothers completed the same questionnaires as in Study 1. Results for the Online Grandmothers Study indicate links between grandmothers' value of positive emotion and better social skills, particularly for African American families. Further, for Appalachian families, results indicate a link between grandmothers' belief in parental guidance of children's emotions and children's better social skills. Findings illustrate the importance of grandmothers in underrepresented families and as influences on children's social skills.