T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy

HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18). Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that enhancing the cytolytic activity of Nef-specific T-cells may lead to reductions in infected cell frequencies, even in the absence of therapeutic latency reversal

Poled polymers for frequency doubling of diode lasers

The design and characterization of methylmethacrylate copolymers with nonlinear optical 4-alkoxy-4'-alkylsulfone stilbene sidechains, which are transparent down to 410 nm are reported. A fairly stable, polar orientation was obtained using elec. field poling, resulting in a reasonably high nonlinearity (d33 ?9 pm/V). [on SciFinder (R)

Knowledge, Attitudes, and Perceptions of Skin Cancer Clinical Trials in the Hispanic Population

To determine the factors that might limit Hispanic patients from participating in dermatological clinical trials. From January 2022 to July 2022, we administered a 31-item, in-person questionnaire to patients recruited in the waiting area of the Caridad Center, one of the largest free clinics in the United States with a predominately Hispanic population, and a nearby private primary care clinic. Overall, Hispanic patients agreed significantly more with statements in the domain of attitude and behavioral beliefs compared to non-Hispanic survey respondents. The Hispanic ethnicity was associated with increased odds of agreeing with the following statements: "My community would really benefit from skin cancer clinical trials" (OR=0.52; 95% CI 0.30, 0.92), "My participation in a skin cancer study would be very good" (OR=0.59; 95% CI 0.35, 0.99), and "I like to do good for others" (OR=0.41; 95% CI 0.22, 0.77). While the United States population is composed of 18.5% Hispanics, they only account for 1% of patients enrolled in clinical trials. This study helps identify potential motivational factors for Hispanic patients to participate in skin cancer clinical trials

PeRsOnalised nutriTion for hEalthy livINg: The PROTEIN project

Personalised nutrition is a novel public health strategy aiming to promote positive diet and lifestyle changes. Tailored dietary and physical activity advice may be more appropriate than a generalised ‘one‐size‐fits‐all’ approach as it is more biologically relevant to the individual. Information and computing technology, smartphones and mobile applications have become an integral part of modern life and thereby present the opportunity for novel methods to encourage individuals to lead a healthier lifestyle. This article introduces the European Union‐funded PROTEIN project (PeRsOnalised nutriTion for hEalthy livINg) consortium and introduces the associated work packages. The primary objective of the PROTEIN project is to produce a novel adaptable mobile application suite based on sound nutrition and physical activity advice from experts in their field, accessible to all population groups, with differing health outcomes, whose behaviour can be tracked with a variety of sensors and health hazard perception. The mobile application ‘ecosystem’ that will be developed by the consortium includes a platform, mobile suite, cloud services, artificial intelligence advisor, game suite, modelling of expert’s knowledge, users’ behaviour data collection, data analysis and a dashboard for healthcare professionals. It is proposed that users will find the provision of personalised nutrition advice and real‐time data capture through a smartphone application useful, and importantly, will be encouraged by this to make positive health behaviour changes