Role of 4-1BB Ligand in Costimulation of T Lymphocyte Growth and its Upregulation on M12 B Lymphomas by cAMP

K46J B lymphomas express a T cell costimulatory activity that is not inhibited by CTLA-4Ig, anti-B7-1, anti-B7-2, anti-intercellular adhesion molecule 1 or antibodies to heat stable antigen. In this paper we report that this costimulatory activity is mediated at least in part by 4-1BB ligand, a member of the tumor necrosis factor (TNF) gene family that binds to 4-1BB, a T cell activation antigen with homology to the TNF/nerve growth factor receptor family. A fusion protein between 4-1BB and alkaline phosphatase (4-1BB-AP) blocks T cell activation by K46J lymphomas in both an antigen-specific system and with polyclonally (anti-CD3) activated T cells. 4-1BB-AP also blocks antigen presentation by normal spleen cells. When the antigen-presenting cells express B7 molecules as well as 4-1BB ligand, we find that B7 molecules and 4-1BB-AP both contribute to T cell activation. These data suggest that 4-1BB ligand plays an important role in costimulation of IL-2 production and proliferation by T cells. The B lymphoma M12 expresses low levels of 4-1BB-L but can be induced to express higher levels by treatment of the B ceils with cAMP, which also induces B7-1 and B7-2 in these cells. Thus cAMP appears to coordinately induce several costimulatory molecules on B cells

Coping under stress: Prefrontal control predicts stress burden during the COVID-19 crisis

The coronavirus (COVID-19) pandemic has confronted millions of people around the world with an unprecedented stressor, affecting physical and mental health. Accumulating evidence suggests that emotional and cognitive self-regulation is particularly needed to effectively cope with stress. Therefore, we investigated the predictive value of affective and inhibitory prefrontal control for stress burden during the COVID-19 crisis. Physical and mental health burden were assessed using an online survey, which was administered to 104 participants of an ongoing at-risk birth cohort during the first wave in April 2020. Two follow-ups were carried out during the pandemic, one capturing the relaxation during summer and the other the beginning of the second wave of the crisis. Prefrontal activity during emotion regulation and inhibitory control were assessed prior to the COVID-19 crisis. Increased inferior frontal gyrus activity during emotion regulation predicted lower stress burden at the beginning of the first and the second wave of the crisis. In contrast, inferior and middle frontal gyrus activity during inhibitory control predicted effective coping only during the summer, when infection rates decreased but stress burden remained unchanged. These findings remained significant when controlling for sociodemographic and clinical confounders such as stressful life events prior to the crisis or current psychopathology. We demonstrate that differential stress-buffering effects are predicted by the neural underpinnings of emotion regulation and cognitive regulation at different stages during the pandemic. These findings may inform future prevention strategies to foster stress coping in unforeseen situations

The importance of high quality real-life social interactions during the COVID-19 pandemic

The coronavirus pandemic has brought about dramatic restrictions to real-life social interactions and a shift towards more online social encounters. Positive social interactions have been highlighted as an important protective factor, with previous studies suggesting an involvement of the amygdala in the relationship between social embeddedness and well-being. The present study investigated the effect of the quality of real-life and online social interactions on mood, and explored whether this association is affected by an individual’s amygdala activity. Sixty-two participants of a longitudinal study took part in a one-week ecological momentary assessment (EMA) during the first lockdown, reporting their momentary well-being and their engagement in real-life and online social interactions eight times per day (N ~ 3000 observations). Amygdala activity was assessed before the pandemic during an emotion-processing task. Mixed models were calculated to estimate the association between social interactions and well-being, including two-way interactions to test for the moderating effect of amygdala activity. We found a positive relationship between real-life interactions and momentary well-being. In contrast, online interactions had no effect on well-being. Moreover, positive real-life social interactions augmented this social affective benefit, especially in individuals with higher amygdala being more sensitive to the interaction quality. Our findings demonstrate a mood-lifting effect of positive real-life social interactions during the pandemic, which was dependent on amygdala activity before the pandemic. As no corresponding effect was found between online social interactions and well-being, it can be concluded that increased online social interactions may not compensate for the absence of real-life social interactions

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Real-time individual benefit from social interactions before and during the lockdown: the crucial role of personality, neurobiology and genes

Contains fulltext : 246516.pdf (Publisher’s version ) (Open Access

Ten Minutes of α-tACS and Ambient Illumination Independently Modulate EEG α-Power

Transcranial alternating current stimulation (tACS) sees increased use in neurosciences as a tool for the exploration of brain oscillations. It has been shown that tACS stimulation in specific frequency bands can result in aftereffects of modulated oscillatory brain activity that persist after the stimulation has ended. The general relationship between persistency of the effect and duration of stimulation is sparsely investigated but previous research has shown that the occurrence of tACS aftereffects depends on the brain state before and during stimulation. Early alpha neurofeedback research suggests that particularly in the alpha band the responsiveness to a manipulation depends on the ambient illumination during measurement. Therefore, in the present study we assessed the brain’s susceptibility to tACS at the individual alpha frequency during darkness compared to ambient illumination. We measured alpha power after 10 min of stimulation in 30 participants while they continuously performed a visual vigilance task. Our results show that immediately after stimulation, the alpha power in the illumination condition for both the stimulated and sham group has increased by only about 7%, compared to about 20% in both groups in the ‘dark’ condition. For the group that did not receive stimulation, the power in darkness remained stable after stimulation, whereas the power in light increased by an additional 10% during the next 30 min. For the group that did receive stimulation, alpha power during these 30 min increased by another 11% in light and 22% in darkness. Since alpha power already increased by about 10% without stimulation, the effect of illumination does not seem to have interacted with the effect of stimulation. Instead, both effects seem to have added up linearly. Although our findings do not show that illumination-induced differences in oscillatory activity influence the susceptibility toward tACS, they stress the importance of controlling for factors like ambient light that might add an independent increase or decrease to the power of brain oscillations during periods, where possible persistent effects of stimulation are explored

Neurostructural traces of early life adversities: A meta-analysis exploring age- and adversity-specific effects

Early life adversities (ELAs) are associated with an increased risk of psychopathology, with studies suggesting a relation to structural brain alterations. Given the recently growing evidence of ELA effects on brain structure, an updated summary is highly warranted. Therefore, anatomical likelihood estimation was used to conduct a coordinate-based meta-analysis of gray matter volume (GMV) alterations associated with ELAs, including sub-analyses for different age groups and maltreatment as specific ELA-type. The analyses uncovered a convergence of pooled ELA-effects on GMV in the right hippocampus and amygdala and the left inferior frontal gyrus, age-specific effects for the right amygdala and hippocampus in children and adolescents, and maltreatment-specific effects for the right perigenual anterior cingulate cortex in adults. These results reveal a possible underlying commonality in the impact of adversity and also point to specific age and maltreatment effects. They suggest neural markers of ELAs in regions involved in socio-emotional functioning and stress regulation, with the potential to be used as targets for interventions designed to buffer or reverse harmful ELA-effects

Neurostructural traces of early life adversities: A meta-analysis exploring age- and adversity-specific effects

Early life adversities (ELAs) are associated with an increased risk of psychopathology, with studies suggesting a relation to structural brain alterations. Given the recently growing evidence of ELA effects on brain structure, an updated summary is highly warranted. Therefore, anatomical likelihood estimation was used to conduct a coordinate-based meta-analysis of gray matter volume (GMV) alterations associated with ELAs, including sub-analyses for different age groups and maltreatment as specific ELA-type. The analyses uncovered a convergence of pooled ELA-effects on GMV in the right hippocampus and amygdala and the left inferior frontal gyrus, age-specific effects for the right amygdala and hippocampus in children and adolescents, and maltreatment-specific effects for the right perigenual anterior cingulate cortex in adults. These results reveal a possible underlying commonality in the impact of adversity and also point to specific age and maltreatment effects. They suggest neural markers of ELAs in regions involved in socio-emotional functioning and stress regulation, with the potential to be used as targets for interventions designed to buffer or reverse harmful ELA-effects