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Linguistic and cultural differences can impede comprehension among potential research participants during the informed consent process, but how researchers and IRBs respond to these challenges in practice is unclear. We conducted in-depth interviews with 15 researchers, research ethics committee (REC) chairs and members from 8 different countries with emerging economies, involved in HIV-related research sponsored by HIV Prevention Trials Network (HPTN), regarding the ethical and regulatory challenges they face in this regard. In the interviews, problems with translating study materials often arose as major concerns. Four sets of challenges were identified concerning linguistic and cultural translations of informed consent documents and other study materials, related to the: (1) context, (2) process, (3) content and (4) translation of these documents. Host country contextual issues included low literacy rates, education (e.g., documents may need to be written below 5th grade reading level), and experiences with research, and different views of written documentation. Certain terms and concepts may not exist in other languages, or have additional connotations that back translations do not always reveal. Challenges arise because of not only the content of word-for-word, literal translation, but the linguistic form of the language, such as tone (e.g., appropriate forms of politeness vs. legalese, seen as harsh), syntax, manner of questions posed, and the concept of the consent); and the contexts of use affect meaning. Problems also emerged in bilateral communications--US IRBs may misunderstand local practices, or communicate insufficiently the reasons for their decisions to foreign RECs. In sum, these data highlight several challenges that have received little, if any, attention in past literature on translation of informed consent and study materials, and have crucial implications for improving practice, education, research and policy, suggesting several strategies, including needs for broader open-source multilingual lexicons, and more awareness of the complexities involved.

Studies on Coding Region Determinant-Binding Protein (CRD-BP) and its orthologs have confirmed their functional role in mRNA stability and localization. CRD-BP is present in extremely low levels in normal adult tissues, but it is over-expressed in many types of aggressive human cancers and in neonatal tissues. Although the exact role of CRD-BP in tumour progression is unclear, cumulative evidence suggests that its ability to physically associate with target mRNAs is an important criterion for its oncogenic role. CRD-BP has high affinity for the 3'UTR of the oncogenic CD44 mRNA and depletion of CRD-BP in cells led to destabilization of CD44 mRNA, decreased CD44 expression, reduced adhesion and disruption of invadopodia formation. Here, we further characterize the CRD-BP-CD44 RNA interaction and assess specific antisense oligonucleotides and small molecule antibiotics for their ability to inhibit the CRD-BP-CD44 RNA interaction. CRD-BP has a high affinity for binding to CD44 RNA nts 2862-3055 with a Kd of 645 nM. Out of ten antisense oligonucleotides spanning nts 2862-3055, only three antisense oligonucleotides (DD4, DD7 and DD10) were effective in competing with CRD-BP for binding to 32P-labeled CD44 RNA. The potency of DD4, DD7 and DD10 in inhibiting the CRD-BP-CD44 RNA interaction in vitro correlated with their ability to specifically reduce the steady-state level of CD44 mRNA in cells. The aminoglycoside antibiotics neomycin, paramomycin, kanamycin and streptomycin effectively inhibited the CRD-BP-CD44 RNA interaction in vitro. Assessing the potential inhibitory effect of aminoglycoside antibiotics including neomycin on the CRD-BP-CD44 mRNA interaction in cells proved difficult, likely due to their propensity to non-specifically bind nucleic acids. Our results have important implications for future studies in finding small molecules and nucleic acid-based inhibitors that interfere with protein-RNA interactions.