Altered reward processing following an acute social stressor in adolescents

Altered reward processing is a transdiagnostic factor implicated in a wide range of psychiatric disorders. While prior animal and adult research has shown that stress contributes to reward dysfunction, less is known about how stress impacts reward processing in youth. Towards addressing this gap, the present study probed neural activation associated with reward processing following an acute stressor. Healthy adolescents (n = 40) completed a clinical assessment, and fMRI data were acquired while participants completed a monetary guessing task under a no-stress condition and then under a stress condition. Based on prior literature, analyses focused on a priori defined regions-of-interest, specifically the striatum (win trials) and dorsal anterior cingulate cortex [dACC] and insula (loss trials). Two main findings emerged. First, reward-related neural activation (i.e., striatum) was blunted in the stress relative to the no-stress condition. Second, the stress condition also contributed to blunted neural response following reward in loss-related regions (i.e., dACC, anterior insula); however, there were no changes in loss sensitivity. These results highlight the importance of conceptualizing neural vulnerability within the presence of stress, as this may clarify risk for mental disorders during a critical period of development

Field Demonstration of a Real-time Non-intrusive Monitoring System for Condition-based Maintenance

The performance of important electrical loads on mission critical systems like warships or off-shore platforms is often tracked by dedicated monitoring equipment. Individual monitoring of each load is expensive and risky. Expense occurs because of the need for individual sensors and sensor wiring for every load of interest. Reliability is compromised because detected failures or fault conditions might legitimately be due to load failure, but might also be due to errors or failure in the sensor network or recording instruments. The power distribution network on a warship could be pressed into “dual-use” service, providing not only power distribution but also a diagnostic monitoring capability based on observations of the way in which loads draw power from the distribution service. This paper describes field tests of a prototype system that monitors multiple loads using existing electrical wiring. Initial results are presented from a device that monitors a small collection of motors and two other devices that monitor an entire engine room.Grainger Foundation; National Science Foundation (U.S.); United States. National Aeronautics and Space Administration; United States. Coast Guard; United States. Office of Naval Research. Electric Ship Research and Development Consortium; NAVSEA; University of North Carolin

Microglia Actively Remodel Adult Hippocampal Neurogenesis through the Phagocytosis Secretome

During adult hippocampal neurogenesis, most newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of intracellular contents. Here, we propose that phagocytosis is not merely passive corpse removal but has an active role in maintaining neurogenesis. First, we found that neurogenesis was disrupted in male and female mice chronically deficient for two phagocytosis pathways: the purinergic receptor P2Y12, and the tyrosine kinases of the TAM family Mer tyrosine kinase (MerTK)/Axl. In contrast, neurogenesis was transiently increased in mice in which MerTK expression was conditionally downregulated. Next, we per-formed a transcriptomic analysis of the changes induced by phagocytosis in microglia in vitro and identified genes involved in metabolism, chromatin remodeling, and neurogenesis-related functions. Finally, we discovered that the secretome of phagocytic microglia limits the production of new neurons both in vivo and in vitro. Our data suggest that microglia act as a sensor of local cell death, modulating the balance between proliferation and survival in the neurogenic niche through the phagocytosis secretome, thereby supporting the long-term maintenance of adult hippocampal neurogenesis.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (http://www. mineco.gob.es) with FEDER funds to A.S. (BFU2012-32089 and RYC-2013-12817) to A.S. and J.V. (BFU2015-66689); a Leonardo Award from the BBVA Foundation to A.S. (IN16,_BBM_BAS_0260); a Basque Government Department of Education project to A.S. (PI_2016_1_0011; http://www.euskadi.eus/basque-government/department-educa- tion/); Ikerbasque start-up funds to J.V.; a Hungarian Research and Development Fund Grant (K116654) to B.S.; a Hungarian Brain Research Program Grant (2017-1.2.1-NKP-2017-00002) to B.S.; a National Institutes of Health Grant (AG060748) to G.L

Acupuncture in the Treatment of Pain in Temporomandibular Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Objectives: The aim of this study is to perform a qualitative and quantitative analysis of the scientific literature regarding the use of acupuncture in the treatment of pain associated with temporomandibular disorders (TMDs). Methods: By using electronic databases, the goal was to search and evaluate all the randomized controlled trials (RCTs) in which acupuncture was used in the management of pain attributed to these clinical entities. For the meta-analysis, an adequate description of the results' statistical data was required along with a comparison of the treatment with a control group using a placebo or sham. Two independent reviewers evaluated the quality of the studies using the Jadad scale. Results: A total of 8 RCTs were selected, and the quality of only 4 was considered acceptable. These 4 studies showed positive results such as reducing pain, improving masticatory function, and increasing maximum interincisal opening. By combining the studies (n=96) and analyzing the results, it was concluded that acupuncture is more effective than placebo in reducing pain intensity in TMD (standardized mean difference 0.83; 95% confidence interval, 0.41-1.25; P=0.00012). Discussion: The results of this meta-analysis suggest that acupuncture is a reasonable adjunctive treatment for producing a shortterm analgesic effect in patients with painful TMD symptoms. Although the results described are positive, the relevance of these results was limited by the fact that substantial bias was present. These findings must be confirmed by future RCTs that improve the methodologic deficiencies of the studies evaluated in this metaanalysis. Key Words: acupuncture, temporomandibular disorders, orofacial pain, randomized controlled trial, meta-analysis, review (Clin J Pain 2010;26:541-550) T emporomandibular disorders (TMDs) refer to various conditions affecting the temporomandibular joint, masticatory muscles, and contiguous tissues components. 1 Different types of painful TMDs are encountered: myogenous or muscle-generated pain; arthrogenous or joint generated pain; or both. 1-4 According to Stohler, 5 between 90% and 95% of TMD patients have facial pain of muscular origin without identifiable structural causes. Among the painful TMD of muscular origin, the most frequent is myofascial pain (MP). 6 At present, the therapeutic management of TMD is approached using a medical multidisciplinary model, and the treatment options range from conservative, noninvasive therapeutic measures to more aggressive treatment interventions. However, in most of the mild and moderate cases of TMD, a significant clinical improvement can be obtained with conservative therapeutic modalities. Acupuncture is an increasingly used treatment modality for the therapeutic management of pain symptoms. A meta-analysis performed by Ter Riet et al 9 showed that the majority of the studies documented positive results. However, the main conclusion obtained from that meta-analysis was that the methodologic quality of the studies analyzed required more evidence. For this reason, the investigators concluded that the effects of acupuncture for chronic pain are doubtful. In terms of TMD and acupuncture treatment, the results obtained were similar to those obtained in an earlier systematic review published in 1999. It is important to emphasize that in the last 10 years, additional studies have been published using acupuncture to treat TMD. This meta-analysis will review the publications of the last 10 years to include the improved evidence that has accumulated over that time. The aim of this study is to perform an analysis that evaluates the quality of the studies and the effectiveness of acupuncture treatment in relieving painful TMD symptomatology

Blood Glucose Levels Regulate Pancreatic β-Cell Proliferation during Experimentally-Induced and Spontaneous Autoimmune Diabetes in Mice

Type 1 diabetes mellitus is caused by immune-mediated destruction of pancreatic beta-cells leading to insulin deficiency, impaired intermediary metabolism, and elevated blood glucose concentrations. While at autoimmune diabetes onset a limited number of beta-cells persist, the cells' regenerative potential and its regulation have remained largely unexplored. Using two mouse autoimmune diabetes models, this study examined the proliferation of pancreatic islet ss-cells and other endocrine and non-endocrine subsets, and the factors regulating that proliferation.We adapted multi-parameter flow cytometry techniques (including DNA-content measurements and 5'-bromo-2'-deoxyuridine [BrdU] incorporation) to study pancreatic islet single cell suspensions. These studies demonstrate that beta-cell proliferation rapidly increases at diabetes onset, and that this proliferation is closely correlated with the diabetic animals' elevated blood glucose levels. For instance, we show that when normoglycemia is restored by exogenous insulin or islet transplantation, the beta-cell proliferation rate returns towards low levels found in control animals, yet surges when hyperglycemia recurs. In contrast, other-than-ss endocrine islet cells did not exhibit the same glucose-dependent proliferative responses. Rather, disease-associated alterations of BrdU-incorporation rates of delta-cells (minor decrease), and non-endocrine islet cells (slight increase) were not affected by blood glucose levels, or were inversely related to glycemia control after diabetes onset (alpha-cells).We conclude that murine beta-cells' ability to proliferate in response to metabolic need (i.e. rising blood glucose concentrations) is remarkably well preserved during severe, chronic beta-cell autoimmunity. These data suggest that timely control of the destructive immune response after disease manifestation could allow spontaneous regeneration of sufficient beta-cell mass to restore normal glucose homeostasis

Climate change drives migratory range shift via individual plasticity in shearwaters.

How individual animals respond to climate change is key to whether populations will persist or go extinct. Yet, few studies investigate how changes in individual behavior underpin these population-level phenomena. Shifts in the distributions of migratory animals can occur through adaptation in migratory behaviors, but there is little understanding of how selection and plasticity contribute to population range shift. Here, we use long-term geolocator tracking of Balearic shearwaters (Puffinus mauretanicus) to investigate how year-to-year changes in individual birds' migrations underpin a range shift in the post-breeding migration. We demonstrate a northward shift in the post-breeding range and show that this is brought about by individual plasticity in migratory destination, with individuals migrating further north in response to changes in sea-surface temperature. Furthermore, we find that when individuals migrate further, they return faster, perhaps minimizing delays in return to the breeding area. Birds apparently judge the increased distance that they will need to migrate via memory of the migration route, suggesting that spatial cognitive mechanisms may contribute to this plasticity and the resulting range shift. Our study exemplifies the role that individual behavior plays in populations' responses to environmental change and highlights some of the behavioral mechanisms that might be key to understanding and predicting species persistence in response to climate change

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