Newcomer knowledge, attitudes, and beliefs about human papillomavirus (HPV) vaccination.

BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted infection in Canada and around the world. Vaccination is an effective prevention strategy, but uptake is low, especially among newcomers to Canada. We sought to understand newcomers' knowledge, attitudes, and beliefs (KAB) on HPV and HPV vaccination and their role in HPV vaccine acceptance. METHODS: Newcomers were defined as individuals born outside Canada, (i.e., individuals born in a different country, the majority of whom are immigrants or refugees, but also includes students and undocumented migrants). Eligible participants were newcomers, aged 16 or older and who could read or write in English, French or Arabic. Surveys were administered in two community health centres in Ottawa, Canada that primarily engage with newcomer populations. Follow-up interviews were conducted either at the community health centre or over the phone, depending on participants' preferences. RESULTS: Fifty participants completed the survey, the majority of whom were women (74%) and spoke Arabic as their first language (54%). Seven participants completed supplemental interviews to complement their survey responses. The majority (70%) of participants had not previously heard of HPV. Less than half (46%) knew that the vaccine is effective in preventing certain types of cancer; nearly 40% incorrectly believed the vaccine could cure HPV. Qualitative interviews supported the survey findings. CONCLUSIONS: Despite a lack of HPV knowledge due to cultural and language barriers, there is still a strong desire among newcomers to receive the vaccine, especially when accompanied by a physician recommendation. Cultural and language-appropriate resources are needed to help newcomers make informed vaccination decisions and promote HPV vaccine uptake.

Healthcare provider perspectives on the uptake of the human papillomavirus vaccine among newcomers to Canada: a qualitative study.

Human papillomavirus is among the most common sexually transmitted infections in the world. Newcomers, defined in Canada as foreign-born individuals who are either immigrants or refugees, but may also include students and undocumented migrants, face numerous barriers to HPV vaccination. This study sought to understand, from the perspective of healthcare providers, barriers and facilitators to HPV vaccination, and recommendations to improve HPV vaccine uptake among newcomers. Semi-structured interviews were conducted with 10 healthcare providers between March and April 2018. Data were analyzed at the manifest level using a Qualitative Content Analysis approach. Categories of barriers to vaccination included: access, communication, knowledge, culture, and provider-related factors. Facilitators included targeted health promotion; understanding the relevance of HPV vaccination; trusting the healthcare system; and cultural sensitivity. Two overarching recommendations were to publicly fund the HPV vaccine, and enhance language- and culturally-appropriate health promotion activities. Further research should explore informational desires and needs from the perspective of newcomers to inform strategies to promote equitable HPV vaccine coverage.

A common polymorphism in the 5' UTR of ERCC5 creates an upstream ORF that confers resistance to platinum-based chemotherapy.

We show that a common polymorphic variant in the ERCC5 5' untranslated region (UTR) generates an upstream ORF (uORF) that affects both the background expression of this protein and its ability to be synthesized following exposure to agents that cause bulky adduct DNA damage. Individuals that harbor uORF1 have a marked resistance to platinum-based agents, illustrated by the significantly reduced progression-free survival of pediatric ependymoma patients treated with such compounds. Importantly, inhibition of DNA-PKcs restores sensitivity to platinum-based compounds by preventing uORF1-dependent ERCC5 expression. Our data support a model in which a heritable 5' noncoding mRNA element influences individuals' responses to platinum-based chemotherapy.

Cap-Independent Translation in Hematological Malignancies.

Hematological malignancies are a heterogeneous group of diseases deriving from blood cells progenitors. Although many genes involved in blood cancers contain internal ribosome entry sites (IRESes), there has been only few studies focusing on the role of cap-independent translation in leukemia and lymphomas. Expression of IRES trans-acting factors can also be altered, and interestingly, BCL-ABL1 fusion protein expressed from "Philadelphia" chromosome, found in some types of leukemia, regulates several of them. A mechanism involving c-Myc IRES and cap-independent translation and leading to resistance to chemotherapy in multiple myeloma emphasize the contribution of cap-independent translation in blood cancers and the need for more work to be done to clarify the roles of known IRESes in pathology and response to chemotherapeutics.

RNA binding protein/RNA element interactions and the control of translation.

A growing body of work demonstrates the importance of post-transcriptional control, in particular translation initiation, in the overall regulation of gene expression. Here we focus on the contribution of regulatory elements within the 5' and 3' untranslated regions of mRNA to gene expression in eukaryotic cells including terminal oligopyrimidine tracts, internal ribosome entry segments, upstream open reading frames and cytoplasmic polyadenylation elements. These mRNA regulatory elements may adopt complex secondary structures and/or contain sequence motifs that allow their interaction with a variety of regulatory proteins, RNAs and RNA binding proteins, particularly hnRNPs. The resulting interactions are context-sensitive, and provide cells with a sensitive and fast response to cellular signals such as hormone exposure or cytotoxic stress. Importantly, an increasing number of diseases have been identified, particularly cancers and those associated with neurodegeneration, which originate either from mutation of these regulatory motifs, or from deregulation of their cognate binding partners.

Translation deregulation in B-cell lymphomas.

B-cell lymphomas are a heterogeneous group of diseases that can arise at different stages of B-cell development, often as a result of errors in the cells' unique ontogeny. Common oncogenic features are often observed, including chromosomal rearrangements, somatic mutations and transcriptional change. Disruption of translation regulation is also frequently implicated in both B-cell lymphoma development and progression. Deregulation of translation in lymphomagenesis can arise through changes to the proteins constituting the translational machinery or to their regulators, and to changes in miRNA (microRNA) expression.

Clinical, endoscopic, and histologic findings distinguish eosinophilic esophagitis from gastroesophageal reflux disease.

BACKGROUND & AIMS: Features of eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) overlap; because they cannot be differentiated on the basis of eosinophil counts alone, it can be a challenge to distinguish these disorders. We aimed to characterize the clinical, endoscopic, and histologic features of EoE and GERD and to identify factors that might be used to differentiate them. METHODS: We performed a retrospective case-control study on data collected from 2000 to 2007. Cases were patients of any age with EoE, as defined by recent consensus guidelines; controls were patients of any age with GERD. Clinical and endoscopic data were collected, and all esophageal biopsy specimens were reassessed by gastrointestinal pathologists. Cases and controls were compared, unconditional logistic regression was performed to develop a model to predict EoE, and receiver operator characteristic curves were constructed. RESULTS: Data from 151 patients with EoE and 226 with GERD were analyzed. Compared with GERD, features that independently predicted EoE included younger age; symptoms of dysphagia; documented food allergies; observations of esophageal rings, linear furrows, white plaques, or exudates by upper endoscopy; an absence of a hiatal hernia, observed by upper endoscopy; a higher maximum eosinophil count; and the presence of eosinophil degranulation observed in biopsy specimens. The area under the curve for this model was 0.934. CONCLUSIONS: We identified a set of readily available and routinely measured variables that differentiate EoE from GERD. Use of this type of analysis with patients suspected to have EoE might lead to more accurate diagnoses.

Canonical initiation factor requirements of the Myc family of internal ribosome entry segments.

Initiation of protein synthesis in eukaryotes requires recruitment of the ribosome to the mRNA and its translocation to the start codon. There are at least two distinct mechanisms by which this process can be achieved; the ribosome can be recruited either to the cap structure at the 5' end of the message or to an internal ribosome entry segment (IRES), a complex RNA structural element located in the 5' untranslated region (5'-UTR) of the mRNA. However, it is not well understood how cellular IRESs function to recruit the ribosome or how the 40S ribosomal subunits translocate from the initial recruitment site on the mRNA to the AUG initiation codon. We have investigated the canonical factors that are required by the IRESs found in the 5'-UTRs of c-, L-, and N-myc, using specific inhibitors and a tissue culture-based assay system, and have shown that they differ considerably in their requirements. The L-myc IRES requires the eIF4F complex and the association of PABP and eIF3 with eIF4G for activity. The minimum requirements of the N- and c-myc IRESs are the C-terminal domain of eIF4G to which eIF4A is bound and eIF3, although interestingly this protein does not appear to be recruited to the IRES RNA via eIF4G. Finally, our data show that all three IRESs require a ternary complex, although in contrast to c- and L-myc IRESs, the N-myc IRES has a lesser requirement for a ternary complex.