Anti-prion activity generated by a novel vaccine formulation

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of domestic and wild cervids in North America. To address possible prevention regimens for CWD, we have used a mouse model system and the Rocky Mountain Laboratory (RML) mouse-adapted scrapie prion strain to screen efficacy of potential vaccine candidates. Three peptides derived from the primary amino acid sequence of the prion protein were conjugated to blue carrier protein (BCP) and formulated in an adjuvant containing M. avium subsp. avium. CL57/BL6 mice were vaccinated and boosted with 50 µg of the carrier protein–peptide conjugate formulation; all vaccines produced a humoral immune response as measured by ELISA. Disease challenge with the RML scrapie prion strain revealed anti-prion activity was generated by the vaccine formulations as measured by a delay in clinical disease onset and prolonged survivorship

Multiple-crystal X-ray topographic characterization of periodically domain-inverted KTiOPO4 crystal

A periodically domain-inverted KTiOPO4 crystal has been characterized for the first time by multiple-crystal multiple-reflection x-ray topography. The striation contrast within the domain- inverted regions has been revealed in high strain-sensitivity reflection topographs. The origin of formation of the striation contrast and the mechanism of domain inversion in KTiOPO4 are discussed in terms of the structural characteristics of KTiOPO4

Germinal ovarian tumors in reproductive age women: Fertility-sparing and outcome

MOGCTs (malignant ovarian germ cell tumors) are rare tumors that mainly affect patients of reproductive age. The aim of this study was to evaluate the fertility and survival outcomes in young women with MOCGTs treated with fertility-sparing surgery (FSS).From 2000 to 2018, data from 28 patients of reproductive age with a diagnosis of MOGCT at the University of Bari were collected. Most received FSS, and in patients treated conservatively, the reproductive outcome and survival were investigated. Data of patient demographics, clinical presentation, oncology marker dosage, staging, type of surgery, histological examination, survival, and reproductive outcome were collected from hospital and office charts. All informed consent was obtained from all patients. The median age was 24 (range: 9-45 years). The majority of the patients had stage IIIC. Twenty-four woman received FSS consisting of unilateral ovariectomy and omentectomy, whereas only 4 women, based on their stage (IIIC), received a radical surgery (hysterectomy with bilateral adnexectomy, lymphadenectomy, and omentectomy). Our study shows that FSS in MOGCTs can produce good results both on reproductive outcomes and on survival. Indeed, in our group, there was only 1 case of exitus as result of recurrence. Furthermore, patients after FSS maintained normal ovarian function and 5 of 5 women who tried to get pregnant succeeded spontaneously. The median follow-up was 90 months (range 3-159).Conservative surgery for MOGCTs should be considered for women of reproductive age who wish to preserve fertility

AI Researchers, Video Games Are Your Friends!

If you are an artificial intelligence researcher, you should look to video games as ideal testbeds for the work you do. If you are a video game developer, you should look to AI for the technology that makes completely new types of games possible. This chapter lays out the case for both of these propositions. It asks the question "what can video games do for AI", and discusses how in particular general video game playing is the ideal testbed for artificial general intelligence research. It then asks the question "what can AI do for video games", and lays out a vision for what video games might look like if we had significantly more advanced AI at our disposal. The chapter is based on my keynote at IJCCI 2015, and is written in an attempt to be accessible to a broad audience.Comment: in Studies in Computational Intelligence Studies in Computational Intelligence, Volume 669 2017. Springe

Inhibitory 2B4 contributes to NK cell education and immunological derangements in XLP1 patients

X-linked lymphoproliferative disease 1 (XLP1) is an inherited immunodeficiency, caused by mutations in SH2D1A encoding Signaling Lymphocyte Activation Molecule (SLAM)-associated protein (SAP). In XLP1, 2B4, upon engagement with CD48, has inhibitory instead of activating function. This causes a selective inability of cytotoxic effectors to kill EBV-infected cells, with dramatic clinical sequelae. Here, we investigated the NK cell education in XLP1, upon characterization of killer Ig-like receptor (KIR)/KIR-L genotype and phenotypic repertoire of self-HLA class I specific inhibitory NK receptors (self-iNKRs). We also analyzed NK-cell cytotoxicity against CD48+ or CD48− KIR-ligand matched or autologous hematopoietic cells in XLP1 patients and healthy controls. XLP1 NK cells may show a defective phenotypic repertoire with substantial proportion of cells lacking self-iNKR. These NK cells are cytotoxic and the inhibitory 2B4/CD48 pathway plays a major role to prevent killing of CD48+ EBV-transformed B cells and M1 macrophages. Importantly, self-iNKR defective NK cells kill CD48− targets, such as mature DCs. Self-iNKR− NK cells in XLP1 patients are functional even in resting conditions, suggesting a role of the inhibitory 2B4/CD48 pathway in the education process during NK-cell maturation. Killing of autologous mature DC by self-iNKR defective XLP1 NK cells may impair adaptive responses, further exacerbating the patients’ immune defect

Understanding the nature of psychiatric comorbidity in migraine: A systematic review focused on interactions and treatment implications

Background: Migraine is a highly prevalent and disabling neurological disorder which is commonly linked with a broad range of psychiatric comorbidities, especially among subjects with migraine with aura or chronic migraine. Defining the exact nature of the association between migraine and psychiatric disorders and bringing out the pathophysiological mechanisms underlying the comorbidity with psychiatric conditions are relevant issues in the clinical practice. Methods: A systematic review of the most relevant studies about migraine and psychiatric comorbidity was performed using "PubMed", "Scopus", and "ScienceDirect" electronic databases from 1 January 1998 to 15 July 2018. Overall, 178 studies met our inclusion criteria and were included in the current review. Results: According to the most relevant findings of our overview, the associations with psychiatric comorbidities are complex, with a bidirectional association of major depression and panic disorder with migraine. Importantly, optimizing the pharmacological and non-pharmacological treatment of either migraine or its psychiatric comorbidities might help clinicians to attenuate the burden of both these conditions. Conclusions: The available data highlight the need for a comprehensive evaluation of psychiatric disorders in migraine in order to promote an integrated model of care and carefully address the burden and psychosocial impairment related to psychiatric comorbidities in migraine

Patient and practice level factors associated with seasonal influenza vaccine uptake among at-risk adults in England, 2011 to 2016:An age-stratified retrospective cohort study

We sought to gain insights into the determinants of seasonal influenza vaccine (SIV) uptake by conducting an age-stratified analysis (18-64 and 65+) of factors associated with SIV uptake among at-risk adults registered to English practices. Records for at-risk English adults between 2011 and 2016 were identified using the Clinical Practice Research Datalink database. SIV uptake was assessed annually. The associations of patient, practice, and seasonal characteristics with SIV uptake were assessed via cross-sectional and longitudinal analyses, using mixed-effects and general estimating equation logistic regression models. Overall SIV uptake was 35.3% and 74.0% for adults 18-64 and 65+, respectively. Relative to white patients, black patients were least likely to be vaccinated (OR18-64: 0.82 (95% CI: 0.80, 0.85); OR65+: 0.59 (95% CI: 0.56, 0.62)), while Asian patients among 18-64 year olds were most likely to be vaccinated (OR18-64: 1.10 (95% CI: 1.07, 1.13)). Females were more likely than males to be vaccinated among 18-64 year olds (OR18-64: 1.19 (95% CI: 1.18, 1.20)). Greater socioeconomic deprivation was associated with decreased odds of uptake among older patients (OR65+: 0.74 (95% CI: 0.71, 0.77)). For each additional at-risk condition, odds of uptake increased (OR18-64: 2.33 (95% CI: 2.31, 2.36); OR65+: 1.39 (95% CI: 1.38, 1.39)). Odds of uptake were highest among younger patients with diabetes (OR18-64: 4.25 (95% CI: 4.18, 4.32)) and older patients with chronic respiratory disease (OR65+: 1.60 (95% CI: 1.58, 1.63)), whereas they were lowest among morbidly obese patients of all ages (OR18-64: 0.68 (95% CI: 0.67, 0.70); OR65+: 0.97 (95% CI: 0.94, 0.99)). Prior influenza season severity and vaccine effectiveness were marginally predictive of uptake. Our age-stratified analysis uncovered SIV uptake disparities by ethnicity, sex, age, socioeconomic deprivation, and co-morbidities, warranting further attention by GPs and policymakers alike