Early maladaptive schemas and ICD-11 CPTSD symptoms: Treatment considerations

ObjectivesEarly maladaptive schemas (EMS) can result from adverse interpersonal traumatic experiences. The ICD-11 updated the concept of disorders following traumatic experiences with the new disorder of complex post-traumatic stress disorder (CPTSD). There is now a need to develop and test interventions for CPTSD. An essential step in identifying interventions that are particularly relevant to the treatment of CPTSD is to explore psychological constructs associated more closely with CPTSD compared to PTSD. The current study explored the associations of EMS with PTSD and CPTSD.DesignThe sample consisted of 603 adults (mean age = 41.65, SD = 13.8), recruited through social media and e-mails, and who responded to an online questionnaire.MethodsParticipants completed measures of demographic, traumatic life events, EMS, PTSD and CPTSD symptoms.ResultsOverall, results suggest that participants with CPTSD present with higher schema elevations across all schemas compared to those with PTSD or no diagnosis. Secondly, the schemas of emotional deprivation, abandonment/instability, social isolation/alienation, defectiveness/shame, enmeshment/undeveloped self, subjugation, emotional inhibition and insufficient self-control/self-discipline were significantly associated with the symptom clusters of CPTSD. Finally, results indicate that different schemas form significant associations with the individual symptom clusters of CPTSD.ConclusionsAlthough results require replication in clinical samples, initial findings suggest that specific EMS may be important psychological correlates of CPTSD symptoms. Wider treatment considerations of these findings are discussed

Human cytomegalovirus long noncoding RNA4.9 regulates viral DNA replication

Viruses are known for their extremely compact genomes composed almost entirely of protein-coding genes. Nonetheless, four long noncoding RNAs (lncRNAs) are encoded by human cytomegalovirus (HCMV). Although these RNAs accumulate to high levels during lytic infection, their functions remain largely unknown. Here, we show that HCMV-encoded lncRNA4.9 localizes to the viral nuclear replication compartment, and that its depletion restricts viral DNA replication and viral growth. RNA4.9 is transcribed from the HCMV origin of replication (oriLyt) and forms an RNA-DNA hybrid (R-loop) through its G+C-rich 5’ end, which may be important for the initiation of viral DNA replication. Furthermore, targeting the RNA4.9 promoter with CRISPR-Cas9 or genetic relocalization of oriLyt leads to reduced levels of the viral single-stranded DNA-binding protein (ssDBP), suggesting that the levels of ssDBP are coupled to the oriLyt activity. We further identified a similar, oriLyt-embedded, G+C-rich lncRNA in murine cytomegalovirus (MCMV). These results indicate that HCMV RNA4.9 plays an important role in regulating viral DNA replication, that the levels of ssDBP are coupled to the oriLyt activity, and that these regulatory features may be conserved among betaherpesviruses

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Stress&amp;Worldview

ניסוי במסגרת הקורס פסיכולוגיה ניסויית תשע"

GROWTH MINDSET, SCHOOL CONTEXT, AND MATHEMATICS ACHIEVEMENT IN INDONESIA: A MULTILEVEL MODEL

Shifting students to a growth mindset can increase their achievements. Nevertheless, only a few studies have been conducted on this topic in developing countries. This study aims to examine the relationship between growth mindset, school context, and mathematics achievement in Indonesia. Using a multilevel model on the PISA 2018 data, this study explored the variables that contributed to mathematics achievement. The multilevel analysis showed that students’ gender, growth mindset, index of economic social, and cultural status were statistically significant predictors of students’ mathematics achievement. Girls have been reported to have a higher mathematics achievement than boys in Indonesia. As the students’ growth mindset increases, so do their mathematics achievement

Economic Aspects of Bovine Ephemeral Fever (BEF) Outbreaks in Dairy Cattle Herds

Bovine ephemeral fever virus (BEFV) is an arthropod-borne virus (arbovirus) transmitted by blood-feeding insects (mosquitoes and Culicoides biting midges). While the dispersal of arboviral diseases such as bovine ephemeral fever (BEF) into naive areas is often the result of globalization and animal movement, the endemization and local outbreaks of these diseases are mainly influenced by environmental changes. Climate change affects the activity, distribution, dynamics, and life cycles of these vectors (arthropods), the replication of viruses within their vectors, and weakens animal’s immune systems. Although BEF does not currently occur in the Americas and Europe (other than in the western regions of Turkey), the risk of BEFV emergence, spread, and endemization in Europe is real. Over the past two decades, arboviruses such as the bluetongue virus (BTV) and Schmallenberg virus (SBV) have emerged in Europe without warning and caused significant losses to the dairy and meat industries. Since the European cattle population has never been exposed to BEFV, the economic losses to dairy and beef production in this continent due to the reduction in milk production, loss of valuable cows, and abortion, should BEF emerge, would probably be considerable. Moreover, arboviruses can also cause substantial financial damage due to restrictions on animal trade and transportation, like the current EHDV-8 outbreak in the Mediterranean basin. In this study, we used national data stored in the Israeli herd book to examine the economic aspects of BEF outbreaks in affected dairy cattle farms countrywide. Our results demonstrate that BEF outbreaks can have immediate and delayed effects, causing severe economic losses due to culling (loss of valuable cows) and a reduction in milk production that affects dairy farm income for months after clinical diagnosis. To our knowledge, this is the first extensive study on the impact of a BEF outbreak at a population level, enabling to conduct accurate risk assessments in future cases of BEFV emergence and re-emergence

Acceptability of the dengue vaccination among parents in urban poor communities of Quezon City, Philippines before and after vaccine suspension

Abstract Objective The study aims to illustrate the acceptability of the dengue vaccine before and after the dengue vaccination suspension in urban poor communities in Quezon City, Philippines. Results There were 12 interviews conducted in November 2017 and 5 focus group discussions in January 2018, a month after vaccine program suspension with 41 participants. All participants were selected through purposive criterion sampling. Thematic analysis showed acceptability of the dengue vaccine was associated with parental experience with vaccination and dengue, trust in public health institutions and communication received by parents. Post-dengue vaccination suspension triangulation indicated that the parents regretted the experience, trust to public institutions was eroded and the communication strategy was deemed inadequate. This led to low vaccine acceptability post-vaccine suspension

Matrix metalloproteinase 12 promotes tumor propagation in the lung

International audienc