Sexual behaviour among Kenyan adolescents enrolled in an efficacy trial of a smartphone game to prevent HIV: a cross-sectional analysis of baseline data.

Sexual behaviour of adolescents is contextual, with various determinants affecting sexual activity and age of sexual debut. Insight into sexual activity among young adolescents has the potential to influence appropriate sexual and reproductive health interventions. For this analysis, adolescents were recruited as part of the Tumaini smartphone game efficacy trial. Data collection included a self-administered behavioural survey and blood test for HIV and HSV-2. Descriptive statistics were calculated for demographics and measures of sexual behaviour and behavioural intent based on gender and sexual experience, with associations assessed using chi-square tests, t-tests and Wilcoxon rank sum tests as appropriate. We enrolled 996 adolescents, mean age 14 years and 2.2% HSV-2 positivity. Overall, 15% of the adolescents were sexually experienced, this being associated with lower socio-economic status (p = 0.01), household food insecurity (p = 0.008), a living situation without both parents (p < 0.01), substance use (p = 0.02), no adult conversation about future goals (p = 0.003), conversations about condoms (p = 0.01), with some gender disparity within these factors. Among those sexually experienced, 21.7% reported unwilling sex; 17.5% had engaged in transactional sex; 57.8% had willing first sex, of whom 60.9% reported no condom use. Among those abstaining, female adolescents were less likely to contemplate condom use at first sex (p = 0.006). Our findings determine that young sexually active adolescents are likely engaging in unprotected sex and having unwilling sexual experiences. Socio-economic status, living situation and parental monitoring remain significant factors associated with sexual experience among young adolescents. In this context, early adolescence is an opportunity to provide age- and developmentally appropriate education about safer sex practices.Trial registration: ClinicalTrials.gov identifier: NCT04437667.

The Efficacy of a Smartphone Game to Prevent HIV Among Young Africans: Protocol for a Randomized Controlled Trial in the Context of COVID-19.

BACKGROUND: Adolescents contribute slightly less than one-third of all new HIV infections in sub-Saharan Africa. There is a need for more effective intervention approaches to help young adolescents safely navigate through adolescence and into adulthood. We are assessing the efficacy of Tumaini, a smartphone game designed to prevent HIV among young Africans. Against the background of COVID-19, meaningful alteration of the research protocol was necessary to ensure successful implementation and retention of the study participants in ongoing research. OBJECTIVE: The objective of our protocol is to determine (1) if Tumaini delays sexual debut and increases condom use at first sex and (2) whether it influences behavioral mediators of early and unprotected sex. METHODS: Participants were recruited from Kisumu County in Western Kenya. This study is a 2-arm, individual-randomized controlled trial that enrolled 1004 adolescents aged between 12 years and 15 years. The intervention arm participants are playing Tumaini, while the control arm is provided with Brainilis, a commercially available control game. The study period will last 45 months. At baseline, participants in both arms completed a baseline survey and biological testing for HIV and herpes simplex virus, type 2 (HSV-2); participants will have annual game play periods in years 1-3. They will also complete a total of 12 follow-up surveys. At endline, repeat biological testing will be conducted. Protocol adaptations were necessitated by the COVID-19 pandemic and implemented in accordance with local public health guidelines. RESULTS: Participants were enrolled between October 2020 and November 2020. We plan to complete study procedures in September 2024. The enrolled participant sample was 50.1% (499/996) female and had a mean age of 14.0 (SD 0.6) years. CONCLUSIONS: This ongoing research demonstrates that, with appropriate revisions to planned protocol activities guided by the need to maintain study integrity, protect both study participants and staff, and adhere to institutional review board and local health authority guidelines, human subject research is possible in the context of a global pandemic. If the trial demonstrates efficacy, Tumaini would provide an alternative, remote means of delivering age-appropriate education to adolescents on safer sex, HIV prevention, and effective life skills on a highly scalable, low-cost, and culturally adaptable platform. TRIAL REGISTRATION: ClinicalTrials.gov NCT04437667; https://clinicaltrials.gov/ct2/show/NCT04437667. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35117.

Electrochemical characterization of the stimuli-response of surface-immobilized elastin-like polymers.

Elastin-like polymers (ELPs) are frequently used in a variety of bioengineering applications because of their stimuli-responsive properties. Above their transition temperature, ELPs will adopt different structures that promote intra- and intermolecular hydrophobic contacts to minimize unfavorable interactions with an aqueous environment. We electrochemically characterize the stimuli-responsive behavior of surface-immobilized ELPs corresponding to two proposed states: extended and collapsed. In the extended state the ELPs are more solvated. In the collapsed state, triggered by introducing an environmental stimulus, non-polar intramolecular contacts within ELPs are favored, resulting in quantifiable morphological changes on the surface characterized using electrochemical impedance spectroscopy (EIS). Charge transfer resistance, a component of impedance, was shown to increase after exposing an ELP modified electrode to a high salt concentration environment (3.0 M NaCl). An increase in charge transfer resistance indicates an increase in the insulating layer on the electrode surface consistent with the proposed mechanism of collapse, as the ELPs have undergone morphological changes to hinder the kinetics of the redox couple exchange. Further characterization of the surface-immobilized ELPs showed a reproducible surface modification, as well as reversibility and tunability of the stimuli-response.

Flow imaging microscopy as a novel tool for high-throughput evaluation of elastin-like polymer coacervates.

Biological and bioinspired polymer microparticles have broad biomedical and industrial applications, including drug delivery, tissue engineering, surface modification, environmental remediation, imaging, and sensing. Full realization of the potential of biopolymer microparticles will require methods for rigorous characterization of particle sizes, morphologies, and dynamics, so that researchers may correlate particle characteristics with synthesis methods and desired functions. Toward this end, we evaluated biopolymer microparticles using flow imaging microscopy. This technology is widely used in the biopharmaceutical industry but is not yet well-known among the materials community. Our polymer, a genetically engineered elastin-like polypeptide (ELP), self-assembles into micron-scale coacervates. We performed flow imaging of ELP coacervates using two different instruments, one with a lower size limit of approximately 2 microns, the other with a lower size limit of approximately 300 nanometers. We validated flow imaging results by comparison with dynamic light scattering and atomic force microscopy analyses. We explored the effects of various solvent conditions on ELP coacervate size, morphology, and behavior, such as the dispersion of single particles versus aggregates. We found that flow imaging is a superior tool for rapid and thorough particle analysis of ELP coacervates in solution. We anticipate that researchers studying many types of microscale protein or polymer assemblies will be interested in flow imaging as a tool for quantitative, solution-based characterization.

Guide to Selecting a Biorecognition Element for Biosensors.

Biosensors are powerful diagnostic tools defined as having a biorecognition element for analyte specificity and a transducer for a quantifiable signal. There are a variety of different biorecognition elements, each with unique characteristics. Understanding the advantages and disadvantages of each biorecognition element and their influence on overall biosensor performance is crucial in the planning stages to promote the success of novel biosensor development. Therefore, this review will focus on selecting the optimal biorecognition element in the preliminary design phase for novel biosensors. Included is a review of the typical characteristics and binding mechanisms of various biorecognition elements, and how they relate to biosensor performance characteristics, specifically sensitivity, selectivity, reproducibility, and reusability. The goal is to point toward language needed to improve the design and development of biosensors toward clinical success.

Effects of Emulsion Composition on Pulmonary Tobramycin Delivery During Antibacterial Perfluorocarbon Ventilation.

BACKGROUND: The effectiveness of inhaled aerosolized antibiotics is limited by poor ventilation of infected airways. Pulmonary delivery of antibiotics emulsified within liquid perfluorocarbon [antibacterial perfluorocarbon ventilation (APV)] may solve this problem through better airway penetration and improved spatial uniformity. However, little work has been done to explore emulsion formulation and the corresponding effects on drug delivery during APV. This study investigated the effects of emulsion formulation on emulsion stability and the pharmacokinetics of antibiotic delivery via APV. METHODS: Gravity-driven phase separation was examined in vitro by measuring emulsion tobramycin concentrations at varying heights within a column of emulsion over 4 hours for varying values of fluorosurfactant concentration (Cfs = 5-48 mg/mL H2O). Serum and pulmonary tobramycin concentrations in rats were then evaluated following pulmonary tobramycin delivery via aerosol or APV utilizing sufficiently stable emulsions of varying aqueous volume percentage (Vaq = 1%-5%), aqueous tobramycin concentration (Ct = 20-100 mg/mL), and Cfs (15 and 48 mg/mL H2O). RESULTS: In vitro assessment showed sufficient spatial and temporal uniformity of tobramycin dispersion within emulsion for Cfs ≥15 mg/mL H2O, while lower Cfs values showed insufficient emulsification even immediately following preparation. APV with stable emulsion formulations resulted in 5-22 times greater pulmonary tobramycin concentrations at 4 hours post-delivery relative to aerosolized delivery. Concentrations increased with emulsion formulations utilizing increased Vaq (with decreased Ct) and, to a lesser extent, increased Cfs. CONCLUSIONS: The emulsion stability necessary for effective delivery is retained at Cfs values as low as 15 mg/mL H2O. Additionally, the pulmonary retention of antibiotic delivered via APV is significantly greater than that of aerosolized delivery and can be most effectively increased by increasing Vaq and decreasing Ct. APV has been further proven as an effective means of pulmonary drug delivery with the potential to significantly improve antibiotic therapy for lung disease patients.

Progression of regulatory gene expression states in fetal and adult pro-T-cell development.

Precursors entering the T-cell developmental pathway traverse a progression of states characterized by distinctive patterns of gene expression. Of particular interest are regulatory genes, which ultimately control the dwell time of cells in each state and establish the mechanisms that propel them forward to subsequent states. Under particular genetic and developmental circumstances, the transitions between these states occur with different timing, and environmental feedbacks may shift the steady-state accumulations of cells in each state. The fetal transit through pro-T-cell stages is faster than in the adult and subject to somewhat different genetic requirements. To explore causes of such variation, this review presents previously unpublished data on differentiation gene activation in pro-T cells of pre-T-cell receptor-deficient mutant mice and a quantitative comparison of the profiles of transcription factor gene expression in pro-T-cell subsets of fetal and adult wildtype mice. Against a background of consistent gene expression, several regulatory genes show marked differences between fetal and adult expression profiles, including those encoding two basic helix-loop-helix antagonist Id factors, the Ets family factor SpiB and the Notch target gene Deltex1. The results also reveal global differences in regulatory alterations triggered by the first T-cell receptor-dependent selection events in fetal and adult thymopoiesis.