Optimizing T-cell receptor avidity with somatic hypermutation

Adoptive transfer of T cells that have been genetically modified to express an antitumor T-cell receptor (TCR) is a potent immunotherapy, but only if TCR avidity is sufficiently high. Endogenous TCRs specific to shared (self) tumor-associated antigens (TAAs) have low affinity due to central tolerance. Therefore, for effective therapy, anti-TAA TCRs with higher and optimal avidity must be generated. Here, we describe a new in vitro system for directed evolution of TCR avidity using somatic hypermutation (SHM), a mechanism used in nature by B cells for antibody optimization. We identified 44 point mutations to the Pmel-1 TCR, specific for the H-2D^b-gp100_25-33 melanoma antigen. Primary T cells transduced with TCRs containing two or three of these mutations had enhanced activity in vitro. Furthermore, the triple-mutant TCR improved in vivo therapy of tumor-bearing mice, which exhibited improved survival, smaller tumors and delayed or no relapse. TCR avidity maturation by SHM may be an effective strategy to improve cancer immunotherapy.     

The Effects of Twitter Users’ Gender and Weight on Viral Behavioral Intentions Toward Obesity-Related News

In this study, male and female participants were exposed to identical news stories covering obesity topics paired with tweets from Twitter users. Our study aimed at understanding how obesity-related news combined with user-generated social media posts (i.e., tweets) affect consumers’ evaluations of online content and viral behavioral intentions (the intentions to like, share, and comment). An experiment (N = 316) explored how gender and weight of a Twitter user (tweeter) affect participants’ evaluations and viral behavioral intentions toward news stories. Participants differed in their evaluations of and viral behavioral intentions for news stories as a function of Twitter users’ gender and weight, as well as participants’ gender. While participants expressed more favorable attitudes toward news stories paired with tweets by overweight than healthy females (with the opposite true for tweets by male users), participants expressed greater viral behavioral intentions for news stories paired with tweets by healthy weight than overweight user. These effects were more pronounced among male than female participants. Findings are discussed within the context of social media posts and their persuasive effects in relation to attitude and behavior changes.     

Math anxiety,self‐efficacy,and ability in British undergraduate nursing students

Nurses need to be able to make drug calculations competently. In this study, involving 229 second year British nursing students, we explored the influence of mathematics anxiety, self‐efficacy, and numerical ability on drug calculation ability and determined which factors would best predict this skill. Strong significant relationships (p < .001) existed between anxiety, self‐efficacy, and ability. Students who failed the numerical and/or drug calculation ability tests were more anxious (p < .001) and less confident (p ≤ .002) in performing calculations than those who passed. Numerical ability made the strongest unique contribution in predicting drug calculation ability (beta = 0.50, p < .001) followed by drug calculation self‐efficacy (beta = 0.16, p = .04). Early testing is recommended for basic numerical skills. Faculty are advised to refresh students' numerical skills before introducing drug calculations. © 2012 Wiley Periodicals, Inc. Res Nurs Health 35:178–186, 2012     

Injecting drug use among gay and bisexual men in Sydney: prevalence and associations with sexual risk practices and HIV and hepatitis C infection

Injecting drug use is commonly reported among gay and bisexual men in Australia. We examined the prevalence and covariates of injecting drug use among men participating in the Sydney Gay Community Periodic Survey between 2004–06 and 2011. In 2004–06, data was collected about which drugs were injected, while in 2011, data was collected about hepatitis C (HCV) and esoteric sexual practices. In 2004–06, 5.6 % of men reported injecting drugs in the previous 6 months; 3.4 % reported methamphetamine injection and 0.4 % heroin injection. In 2011, men who injected drugs were less likely to be employed full-time, and more likely to be HCV-positive, HIV-positive, to have used party drugs for sex, and to have engaged in esoteric sexual practices. The strong associations between injecting drug use, sexual risk practices and blood-borne virus infection suggests the need for combined sexual health and harm reduction services for gay and bisexual men who inject drugs.     

Viewing oneself as a capable person – experiences of professionals working with older Finnish immigrants

The proportion of older immigrants in the population is expected to increase in Sweden. Research indicates that older immigrants face the double burden of frailty, caused by a weaker health status, and the immigration process. Health promotion interventions can be used to prevent frailty and support healthy ageing in this population. Healthcare professionals are a crucial part of health promotion and the present study aimed to explore healthcare professionals’ experiences of health in context of daily life among older immigrants to and provide a basis for the development of a health promotion intervention targeted at older immigrants. Four focus group discussions were conducted with professionals who worked with home‐dwelling older people from Finland, currently living in Sweden. Participants represented a variety of healthcare professions. Data were analysed using qualitative content analysis. The healthcare professionals perceived that health in daily life was (i) connected to the view of oneself as a capable person and (ii) participants strove to maintain their own origin. The findings highlighted that when planning for health promotion interventions for older immigrants, the point of departure should be to recognise the person as a person and the background of immigration is not the first issue to address. Therefore, a person‐centred health promotion intervention is recommended to open a dialogue between healthcare professionals and older immigrants, so that a common view of the intervention can be reached.