Search

Introduction: Indigenous peoples in Canada have endured and continue to experience the impact of colonization by European settlers. The deleterious manifestations of intergenerational historic trauma (HT) are evidenced in the high HIV/AIDS epidemic-related premature mortality rates among Indigenous men, despite the availability of novel highly active antiretroviral therapies (HAARTs).Aim: The aims of this study were to explore the impact of historic trauma (HT) on treatment adherence and health promoting practices among Indigenous men living with HIV, and how resilience was both expressed and mediated by survivor status.Methods: This interpretive description study incorporated a cultural safety lens. Through partnership with the Vancouver Native Health Society, 36 male HT survivors were recruited using purposive and theoretical sampling. They told their lived experiences and health promoting practices with respect to HAART adherence through interviews and a focus group.Results: Two broad categories (findings) emerged: (1) resilience as facilitator of HAART adherence; and (2) differential views on HT's impact. Resilience was expressed through nine concepts.Conclusion: Most Indigenous men in this study demonstrate health promoting behavior, stay on HAART and have better health and well-being even if the environments they live in are marginalized or heavily stigmatizing. This study shows that areas of strength and adaptation, including factors promoting resilience can be harnessed to foster HAART adherence. With a consideration of these areas of strength and adaptation, this study offers implications for research and recommendations to improve treatment-adherent behavior, fostering healing from HT, and reducing HIV/AIDS-related deaths.

The potential to grow genomic knowledge and harness the subsequent clinical benefits has escalated the building of background variant databases (BVDs) for genetic diagnosis across the globe. Alongside the upsurge of this precision medicine, potential benefits have been highlighted for both rare genetic conditions and other diagnoses. However, with the ever-present “genomic divide,” Indigenous peoples globally have valid concerns as they endure comparatively greater health disparities but stand to benefit the least from these novel scientific discoveries and progress in healthcare. The paucity of Indigenous healthcare providers and researchers in these fields contributes to this genomic divide both in access to, and availability of culturally safe, relevant and respectful healthcare using this genetic knowledge. The vital quest to provide equitable clinical research, and provision and use of genomic services and technologies provides a strong rationale for building BVDs for Indigenous peoples. Such tools would ground their representation and participation in accompanying genomic health research and benefit acquisition. We describe two, independent but highly similar initiatives–the “Silent Genomes” in Canada and the “Aotearoa Variome” in New Zealand–as exemplars that have had to address the aforementioned issues and work to create Indigenous BVDs with these populations. Taking into account the baseline inequities in genomic medicine for Indigenous populations and the ongoing challenges of implementing genomic research with Indigenous communities, we provide a rationale for multiple changes required that will assure communities represented in BVDs, as well as Indigenous researchers, that their participation will maximize benefits and minimize risk.

Within the context of a study about the lived experiences of Indigenous males living with HIV in Vancouver, Canada, we explored the utilization of an innovative method of collecting the narratives of study participants. This article describes and assesses the use of the Life Story Board (LSB) as a potentially rich interview tool for qualitative research and explores the process, as well as its advantages and challenges. The LSB uses sets of cards, markers, and notation on a play board to create a visual representation of a verbal narration about someone’s life situation or story. Five study participants took part in a conventional face-to-face interview and 4 months later were interviewed with the use of the LSB. These study participants were asked toward the end of the LSB session about their experience of being interviewed with and without the LSB. Data were also gathered from the interviewers’ experience. The findings suggested that the LSB offers interesting opportunities when used in qualitative research. Study participants found it to facilitate a reflective and more in-depth narration of their lived experience. The interviewer’s perspective for the most part corroborated these observations.

α-Hydroxy-γ-pyrone-based oxidopyrylium cycloaddition reactions are useful methods for accessing a highly diverse range of oxabicyclo[3.2.1]octane products. Intermolecular variants of the reaction require the formation of a methyl triflate-based pre-ylide salt that upon treatment with base in the presence of alkenes or alkynes leads to α-methoxyenone-containing bicyclic products. Herein, we describe our discovery that the use of ethanol-stabilized chloroform as solvent leads to the generation of α-ethoxyenone-containing bicyclic byproducts. This three-component process was further optimized by gently heating a mixture of a purified version of the oxidopyrylium dimer in the presence of an alcohol prior to addition of a dipolarophile. Using this convenient procedure, several new oxidopyrylium cycloaddition products can be generated in moderate yields. We also highlight the method in a tandem ring-opening/debenzylation method for the generation of α-hydroxytropolones.

Hepatitis B virus (HBV) remains a major human pathogen despite the development of both antiviral drugs and a vaccine, in part because the current therapies do not suppress HBV replication far enough to eradicate the virus. Here, we screened 51 troponoid compounds for their ability to suppress HBV RNaseH activity and HBV replication based on the activities of α-hydroxytropolones against HIV RNaseH, with the goal of determining whether the tropolone pharmacophore may be a promising scaffold for anti-HBV drug development. Thirteen compounds inhibited HBV RNaseH, with the best 50% inhibitory concentration (IC50) being 2.3 μM. Similar inhibition patterns were observed against HBV genotype D and C RNaseHs, implying limited genotype specificity. Six of 10 compounds tested against HBV replication in culture suppressed replication via blocking of viral RNaseH activity, with the best 50% effective concentration (EC50) being 0.34 μM. Eighteen compounds inhibited recombinant human RNaseH1, and moderate cytotoxicity was observed for all compounds (50% cytotoxic concentration [CC50]=25 to 79 μM). Therapeutic indexes ranged from 3.8 to 94. Efficient inhibition required an intact α-hydroxytropolone moiety plus one or more short appendages on the tropolone ring, but a wide variety of constituents were permissible. These data indicate that troponoids and specifically α-hydroxytropolones are promising lead candidates for development as anti-HBV drugs, providing that toxicity can be minimized. Potential anti-RNaseH drugs are envisioned to be employed in combination with the existing nucleos(t)ide analogs to suppress HBV replication far enough to block genomic maintenance, with the goal of eradicating infection., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Methoxytropolones are useful scaffolds for therapeutic development because of their known biological activity and established value in the synthesis of α-hydroxytropolones. Upon treatment with triflic acid, a series of 3-methoxy-8-oxabicyclo[3.2.1]octa-3,6-dien-2-ones rearrange rapidly and cleanly to form methoxytropolones. Interestingly, bicycles that are derived from dimethyl acetylenedicarboxylate (R(2) = R(3) = CO2Me) instead form furans as the major product.