International workshop on immune tolerance induction: consensus recommendations 1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73382/1/j.1365-2516.2007.01497.x.pd

Medical Countermeasures for Radiation Induced Health Effects: Reports of an Interagency Panel Session Held at the NASA Human Research Program Investigator's Workshop, January 26, 2017

An Interagency Panel Session organized by the NASA Human Research Program Space Radiation Program Element (SRPE) was held during the NASA Human Research Program (HRP) Investigators Workshop (IWS) in Galveston, Texas on January 26, 2017 to identify complementary research areas that will advance the testing and development of medical countermeasures (MCM) in support of radioprotection and radiation mitigation on the ground and in space. There were several areas of common interest identified among the various participating agencies. This report provides a summary of the topics discussed by each agency along with potential areas of intersection for mutual collaboration opportunities. Common goals included repurposing of pharmaceuticals, neutraceuticals for use as radioprotectors and/or mitigators, low-dose/chronic exposure paradigms, late effects post-radiation exposure, mixed-field exposures of gamma-neutron, performance decrements, and methods to determine individual exposure levels

CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome.

Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interfered with interactions between the RNA-binding protein Raly and the CCR5 3' untranslated region, protecting CCR5 messenger RNA from Raly-mediated degradation. Reduction in CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ T cells with CCR5-tropic HIV in vitro. These data represent a rare determination of the functional importance of a genome-wide disease association where expression of a lncRNA affects HIV infection and disease progression

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

Impact of HPV vaccination : health gains in the Italian female population

Abstract Background Human papillomavirus (HPV) is the leading cause of cervical cancer and other malignant and benign neoplastic lesions. HPV vaccination has three potential goals: to prevent transmission, infection, and disease. At present, there are no available data about health consequences of HPV immunization in Italy. The aim of this study is to evaluate the effect of current HPV vaccination strategy in Italy. Methods A multistate morbidity-mortality model was developed to estimate the infection process in a theoretical cohort of Italian women. The Markov process considered nine health states (health, anogenital warts, grade 1 and grade 2/3 cervical intraepithelial neoplasia, cervical cancer, anal cancer, death due to cervical cancer, anal cancer and other causes), and 26 transition probabilities for each age group. The model was informed with the available data in national and international literature. Effectiveness of immunization was assumed considering a literature review pertaining to models and vaccination coverage rates observed in Italy. Life expectancy (ex), Quality-Adjusted Life Years (QALYs), Disability-Adjusted Life Years (DALYs), and attributable risk (AR) were estimated for no intervention (cervical cancer screening) and vaccination strategies scenarios. Results The model showed that in a cohort of 100,000 Italian women the e0 is equal to 83.1 years. With current HPV vaccination strategy the e0 achieves 83.2 (+0.1) years. When HPV-related diseases are considered altogether, the QALYs increase from 82.7 to 82.9 (+0.2 QALYs) with no intervention and vaccination strategies respectively. DALYs decrease by 0.6 due to vaccination. Finally, AR is equal to 93 and 265 cases per 100,000 women in population and not vaccinated, respectively. Conclusion When mortality due to cervical cancer is considered, HPV vaccination seems to have a low impact on health unit gains in the Italian female population. Conversely, when several HPV-related and cancer morbidity conditions are included, the effect of vaccination becomes quite remarkable

Now or Later? Emotional Factors and Decision-Making in Cocaine Use Disorder

Cocaine use disorder (CUD) remains a major public health concern, contributing significantly to death and disability. One defining feature of CUD is the repeated use of cocaine at the expense of alternative rewards. While use of cocaine quickly leads to rewarding effects, working towards alternative, long-term goals tends to involve more delay until reward receipt. Rewards are generally perceived as worth less when people must wait longer to receive them, a phenomenon called delay discounting. Individuals with CUD show steep delay discounting, indicating that they perceive the value of the reward as quickly decreasing as the delay increases. This study focuses on the relationship of delay discounting with distress tolerance and depression symptoms, including anhedonia. These factors are functionally significant areas of deficit in CUD and show promise for future treatment. We hypothesized: (1) lower distress tolerance will relate to steeper delay discounting in treatment-seeking individuals with CUD and (2) higher levels of depression symptoms and anhedonia will relate to steeper delay discounting in treatment-seeking individuals with CUD, although we also tested for possible quadratic relationships with discounting. Participants included treatment-seeking individuals with CUD. Distress tolerance was measured using a self-report questionnaire (Distress Tolerance Scale) and a behavioral measure of pain tolerance (Cold Pressor Task). Depression symptoms were self-reported on the Beck Depression Inventory Second Edition, and anhedonia was self-reported on the Snaith-Hamilton Pleasure Scale. To assess the relationship between these factors and temporal decision-making, we used multiple regression analyses with AUClog and log k from the delay discounting task as dependent variables. Results showed that self-reported distress tolerance showed no relationship with delay discounting, but lower levels of physical distress tolerance were associated with steeper delay discounting. Depressive symptoms showed a quadratic relationship with delay discounting, such that low and high levels of depression were associated with steeper delay discounting than moderate levels. Anhedonia showed a quadratic relationship with delay discounting as well, but moderate levels of anhedonia were associated with steeper delay discounting in comparison to low and high levels. Findings provide insight into the distinct relationship which tolerating physical distress may have with delay discounting in CUD. The unique relationships reported here for depression and anhedonia with delay discounting likely indicate differential associations of mood and reward-processing with decision-making in CUD. These findings offer deeper insight into decision-making in this population and a variety of potential treatment targets for further analysis