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Background: Depression is associated with a reduced sensitivity to rewards and low reward-related brain function in cortico-striatal circuitry. A separate literature documents elevated peripheral inflammation in depression. Recently, integrated reward-inflammation models of depression have been proposed. These models draw on work indicating that peripheral inflammatory proteins access the brain, where they lower reward responsiveness. This blunted reward responsiveness is proposed to initiate unhealthy behaviors (substance use, poor diet), as well as sleep disruption and stress generation, which further heighten inflammation. Over time, dysregulation in reward responsiveness and immune signaling may synergize in a positive feedback loop, whereby dysregulation in each system exacerbates dysregulation in the other. Project RISE (Reward and Immune Systems in Emotion) provides a first systematic test of reward-immune dysregulation as a synergistic and dynamic vulnerability for first onset of major depressive disorder and increases in depressive symptoms during adolescence. Methods: This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 300 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13–16 years old, fluent in English, and without a prior major depressive disorder. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the low tail of the dimension in order to increase the likelihood of major depression onsets. At Time 1 (T1), T3, and T5, each a year apart, participants complete blood draws to quantify biomarkers of low-grade inflammation, self-report and behavioral measures of reward responsiveness, and fMRI scans of reward neural activity and functional connectivity. At T1-T5 (with T2 and T4 six months between the yearly sessions), participants also complete diagnostic interviews and measures of depressive symptoms, reward-relevant life events, and behaviors that increase inflammation. Adversity history is assessed at T1 only. Discussion: This study is an innovative integration of research on multi-organ systems involved in reward and inflammatory signaling in understanding first onset of major depression in adolescence. It has the potential to facilitate novel neuroimmune and behavioral interventions to treat, and ideally prevent, depression.

Fear of positive and negative evaluation is maladaptive and may result in psychosocial dysfunction. Although being diagnosed with mood disorders or experiencing childhood trauma may potentially affect fear of evaluation, previous studies examined this phenomenon mostly in social anxiety disorders. To fill this gap, we investigated the relationship between childhood trauma and fear of positive and negative evaluation in individuals with bipolar disorder (BD), depressive disorders (DD), and healthy controls (HC). 43 individuals with BD, 89 with DD, and 65 HC completed clinical interviews and self-report assessments. The relationship between participants' diagnoses and presence of trauma on fear of positive and negative evaluation was examined using ANCOVA. Independently of experiencing childhood trauma, fear of positive evaluation was significantly higher in individuals with mood disorders vs. HC. Fear of negative evaluation was significantly associated with diagnosis-by-trauma interaction. Significantly lower scores were observed in individuals with BD without childhood trauma compared to those with childhood trauma and individuals with DD. Compared to HC, more individuals with mood disorders experienced childhood trauma. While experiencing childhood trauma may increase vulnerability to mood disorders in general, it is especially detrimental for individuals with BD by increasing the risk for developing a fear of negative evaluation.

Previous research indicates that individuals with depressive disorders (DD) have aberrant resting state functional connectivity and may experience memory dysfunction. While resting state functional connectivity may be affected by experiences preceding the resting state scan, little is known about this relationship in individuals with DD. Our study examined this question in the context of object memory. 52 individuals with DD and 45 healthy controls (HC) completed clinical interviews, and a memory encoding task followed by a forced-choice recognition test. A 5-min resting state fMRI scan was administered immediately after the forced-choice task. Resting state networks were identified using group Independent Component Analysis across all participants. A network modeling analysis conducted on 22 networks using FSLNets examined the interaction effect of diagnostic status and memory accuracy on the between-network connectivity. We found that this interaction significantly affected the relationship between the network comprised of the medial prefrontal cortex, posterior cingulate cortex, and hippocampal formation and the network comprised of the inferior temporal, parietal, and prefrontal cortices. A stronger positive correlation between these two networks was observed in individuals with DD who showed higher memory accuracy, while a stronger negative correlation (i.e., anticorrelation) was observed in individuals with DD who showed lower memory accuracy prior to resting state. No such effect was observed for HC. The former network cross-correlated with the default mode network (DMN), and the latter cross-correlated with the dorsal attention network (DAN). Considering that the DMN and DAN typically anticorrelate, we hypothesize that our findings indicate aberrant reactivation and consolidation processes that occur after the task is completed. Such aberrant processes may lead to continuous “replay” of previously learned, but currently irrelevant, information and underlie rumination in depression.

Ana Casadó,1,2 M Lluïsa Sagristá,1 Margarita Mora1 1Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain; 2Communication and CSR Department, Hospital Clinic of Barcelona, Barcelona, Spain Purpose: Irinotecan (CPT-11) and SN-38 – its active metabolite – are alkaloid-derived topoisomerase I interactive compounds widely used in various cancer therapy protocols. To solve the problems associated with the instability of their lactone ring at physiological pH and with the extreme insolubility of SN-38, the development of delivery carriers (eg, liposomes) has been considered a subject of unquestionable medical interest. This article focuses on the development of an alternative protocol to the classical lipid-film hydration procedures to obtain a pharmaceutical formulation for SN-38.Methods: SN-38-loaded liposomes (SN-38lip) were produced by microemulsification, without a prior lipid-film preparation step, and characterized by different methods. Formulation parameters were determined by photon correlation spectroscopy, and the SN-38 entrapment efficiency was evaluated by absorbance spectroscopy. SN-38lip was obtained as a dry, white powder by lyophilization. MTT and LDH assays were conducted to assess the cytotoxic effect of SN-38, both in liposomal (SN-38lip) and solubilized form (SN-38sol); flow cytometry was used to quantify SN-38 uptake and to analyze cell-cycle phase distribution after drug exposure.Results: Microfluidic, stable, and controlled sized, negatively charged liposomes, with high SN-38 incorporation efficiency into egg yolk phosphatidylcholine (EPC)/L-α-dioleoyl-phospathidylserine (DOPS) (9:1) vesicles (SN-38lip), were prepared. A lyophilized powder of SN-38lip, easily reconstitutable while retaining physicochemical parameters, was finally obtained. The efficacy of SN-38lip was assessed by in vitro studies with two tumor cell lines (HeLa and Caco-2) and compared with that of SN-38sol. It demonstrated the highest uptake of SN-38lip, in accordance with its highest cytotoxicity effect, in comparison with that of SN-38sol. In addition, different cell-cycle alterations were induced in both cell lines by the liposomal formulation.Conclusion: The results highlight the potential usefulness of the procured SN-38 liposomal formulation and provide the basis for conducting in vivo studies that allow the development of alternative strategies for colorectal cancer treatment. Keywords: microfluidic liposomes, drug delivery, SN-38, cytotoxicity, drug uptake, cell-cycle analysis

Elevated inflammation is a risk factor for many psychiatric (e.g., depression) and somatic conditions (e.g., rheumatoid arthritis). Inflammation is influenced by psychosocial processes such as emotion regulation. Characterization of which emotion regulation characteristics impact inflammation could help refine psychosocial interventions aimed at normalizing health-harming inflammatory activity for individuals with psychiatric and somatic illnesses. To investigate this issue, we systematically reviewed the literature on associations between a variety of emotion regulation traits and inflammation. Out of 2816 articles identified, 38 were included in the final review. 28 (74%) found that (a) poor emotion regulation is associated with higher inflammation and/or (b) strong emotion regulation skills are associated with lower inflammation. Consistency of results differed as a function of the emotion regulation construct investigated and methodological characteristics. Results were most consistent for studies testing positive coping/social support seeking or broadly defined emotion regulation/dysregulation. Methodologically, studies testing reactivity to a stressor, adopting a vulnerability-stress framework, or using longitudinal data were most consistent. Implications for integrated, transdiagnostic psychoimmunological theories are discussed, as well as recommendations for clinical research.

One of the main reasons for studying a foreign language is communicating with others, but many students do not feel confidently enough when trying to develop their speaking skills. Among adolescents' frequent activities are that of listening to music while paying attention to song lyrics. We hypothesize that these musical experiences could influence their speaking skills. The present study aims to consider different factors that could influence students' speaking proficiency. Among these factors, students' emotional understanding, their willingness to communicate in a FL and their musical experience are considered. One hundred and twenty-four students of English as a foreign language (EFL) in the fourth year of Secondary Education from three different high schools in Spain took part in the study. Oral data were collected through individual interviews and three scales were administered to measure the different factors. Students' musical experience and emotional response to music were measured through The Absorption in Music Scale, their emotional understanding of verbal texts through The Situational Test of Emotional Understanding -- Brief, and their willingness to communicate in the EFL class through Willingness to Communicate Scale. Although no direct connection was found between students' musical experience and their speaking proficiency, results demonstrate that students with high emotional understanding show better speaking skills and that students with musical experience exhibited higher emotional understanding. We detected a significant positive connection between emotional understanding and all the five parameters considered to assess students' speaking proficiency. The connection between willingness to communicate in the EFL class and students' speaking skills is even greater.

Studies over the past two decades have provided relevant data on the relationship between music and reading abilities although they fundamentally refer to aspects of the first language reading process of young children. The foreign language reading acquisition process of adult learners has, in this sense, been less explored. Research in this area refers to working memory as a "common cognitive marker" for musical aptitude and reading ability, but little is known about the relationship between musical aptitude and silent reading fluency of adult foreign language learners, the hallmark of skilled readers. Specifically, this study seeks to determine whether musical aptitude as well as cognitive factors such as working memory, general intelligence and plurilingualism could contribute to the understanding of adults' silent reading abilities in a foreign language. For this purpose, thirty-eight undergraduates, native speakers of German and learners of Spanish, were tested. Additionally, their FL reading comprehension level and their musical training were controlled to categorise the learners. Our data shows a strong association of musical aptitude, working memory, general intelligence and plurilingualism with learners' foreign language silent reading fluency. In addition, a multiple linear regression analysis reveals that musical aptitude and knowledge of different foreign languages influence their silent reading fluency. But when in a second linear regression the lower reading proficiency level (A2) was introduced as a controlling variable, only musical aptitude is significant. In conclusion, further studies on the silent reading capacity of adult foreign language learners need to consider abilities such as musical aptitude and plurilingualism to better understand the whole reading acquisition process.

Ruxolitinib, a JAK1/JAK2 inhibitor, has been shown to have lower thromboembolism rates compared to placebo in polycythemia vera (PV) patients. This meta‐analysis evaluates ruxolitinib's efficacy and safety against best available therapy (BAT) in patients with PV and in hydroxyurea‐resistant/intolerant PV patients. A comprehensive literature search was conducted up to November 2023. We compared ruxolitinib and BAT for efficacy and safety endpoints. Six studies involving 1061 patients were analyzed, with 620 on BAT and 441 on ruxolitinib. Ruxolitinib showed higher hematocrit control (p = 0.015) and treatment response (p = 0.04) compared to BAT. It also significantly improved Myeloproliferative Neoplasms‐Symptom Assessment Form scores (MPN‐SAF) (p < 0.01). Additionally, patients with PV treated with ruxolitinib had higher rates of nonmelanoma skin cancer (p < 0.01). In subgroup analyses focusing on patients resistant or intolerant to hydroxyurea, ruxolitinib maintained its efficacy, significantly improving treatment response (p < 0.01) and significant improvements in MPN‐SAF (p = 0.02) score when compared to BAT. The safety profile was consistent with the overall analyses, showing significantly reduced thromboembolism rates (p = 0.04), increased rates of anemia (p = 0.01), and increased herpes zoster infections (p = 0.02). Ruxolitinib outperforms BAT in PV and patients with PV‐resistant or intolerant to hydroxyurea, offering better hematocrit control and reducing symptomatic burden and thromboembolism risk. Yet, it is associated with higher rates of anemia, herpes infection, and skin cancer. [ABSTRACT FROM AUTHOR]