Beyond community engagement: perspectives on the meaningful involvement of people with HIV and affected communities (MIPA) in HIV cure research in The Netherlands.

BACKGROUND: Meaningful involvement of people with HIV and affected communities in HIV cure research is essential to ensuring that cure research efforts are conducted transparently, socially justly, and ethically. This study set out to investigate how people with HIV and affected communities are involved in cure research in the Netherlands and explore what can be done to optimize involvement and engagement. METHODS: Eighty-five semi-structured online, telephone, and face-to-face interviews were conducted with people with HIV (N = 30), key populations (N = 35), and key informants (KI; N = 20) in the field of HIV. The interviews were analyzed using reflexive thematic analysis. RESULTS: Awareness of the meaningful involvement of people with HIV (MIPA) efforts was low among people with HIV and key populations, which contrasted with KI, who exhibited greater awareness. People with HIV and KI emphasized the importance of MIPA in ensuring the representation of lived experiences in HIV cure research and fostering trust between communities and researchers. Practical implementations of MIPA were unclear, ultimately resulting in difficulties defining MIPA beyond clinical trial participation. People with HIV and key populations also doubted their skills and self-efficacy to make meaningful contributions when confronted with involvement beyond participating in research and clinical trials. CONCLUSIONS: MIPA is crucial for improving the quality, transparency, and ethical conduct of HIV cure research. It emphasizes the need for increased awareness and funding, standardized guidelines to ensure meaningful involvement, and combat tokenism and misconceptions.

Using the Meaningful Involvement of People Living with HIV/AIDS (MIPA) Framework to Assess the Engagement of Sexual Minority Men of Color in the US HIV Response: a Literature Review.

Black and Latino sexual minority men (SMM) continue to be disproportionately impacted by HIV. We utilized eight components of the Meaningful Involvement of People Living with HIV/AIDS (MIPA) framework to assess the engagement of Black and Latino SMM. Thirty-six (36) studies were included in the literature review. Forty-two percent of studies were Black SMM-specific, followed by Latino SMM-specific (31%) studies. Twenty-eight percent of studies were conducted among both groups. Most studies (72%) were intervention-related and focused on HIV prevention. The top five most common methods of community engagement were focus groups (39%), followed by interviews (36%), community-based participatory research (14%), the utilization of community advisory boards or peer mentorship (11%), and the establishment of multi-stakeholder coalitions, observations, or surveys (8%). We documented at least 7 MIPA components in 47% of the included studies. Community-based participatory research was more commonly utilized to engage Latino SMM. Researchers were more likely to initiate the engagement across all included studies. Few studies documented how Black and Latino SMM perceived the engagement. Engagement responsiveness was a well-documented MIPA component. In terms of engagement power dynamics, there were several examples of power imbalances, especially among Black SMM-specific studies. The inclusion of Black and Latino SMM had robust impacts on HIV research and interventions. There were limited examples of engagement capacity and maintenance. This is one of the first studies focused on utilizing MIPA to document the engagement of SMM of color. MIPA served as a useful framework for understanding the engagement of SMM of color in the US HIV response. The engagement of SMM of color is critical to reducing health inequities.

Arteriovenous fistula after robotic partial nephrectomy: Case report and narrative review.

Arteriovenous fistulas (AVF) of the kidney are uncommon. They may be acquired, idiopathic or arise of congenital arteriovenous malformation. Acquired renal AVF are mostly iatrogenic due to the increasing number of mini-invasive nephron surgery. We report a case of renal AVF in a 65-year-old woman previously treated with left robotic partial nephrectomy (PN), which was successfully treated by endovascular coiling.

Assessment of prediction methods for protein structures determined by NMR in CASP14: Impact of AlphaFold2.

NMR studies can provide unique information about protein conformations in solution. In CASP14, three reference structures provided by solution NMR methods were available (T1027, T1029, and T1055), as well as a fourth data set of NMR-derived contacts for an integral membrane protein (T1088). For the three targets with NMR-based structures, the best prediction results ranged from very good (GDT_TS = 0.90, for T1055) to poor (GDT_TS = 0.47, for T1029). We explored the basis of these results by comparing all CASP14 prediction models against experimental NMR data. For T1027, NMR data reveal extensive internal dynamics, presenting a unique challenge for protein structure prediction methods. The analysis of T1029 motivated exploration of a novel method of "inverse structure determination," in which an AlphaFold2 model was used to guide NMR data analysis. NMR data provided to CASP predictor groups for target T1088, a 238-residue integral membrane porin, was also used to assess several NMR-assisted prediction methods. Most groups involved in this exercise generated similar beta-barrel models, with good agreement with the experimental data. However, as was also observed in CASP13, some pure prediction groups that did not use any NMR data generated models for T1088 that better fit the NMR data than the models generated using these experimental data. These results demonstrate the remarkable power of modern methods to predict structures of proteins with accuracies rivaling solution NMR structures, and that it is now possible to reliably use prediction models to guide and complement experimental NMR data analysis.

Novel Bacterial Surface Display System Based on the Escherichia coli Protein MipA.

Bacterial surface display systems have been developed for various applications in biotechnology and industry. Particularly, the discovery and design of anchoring motifs is highly important for the successful display of a target protein or peptide on the surface of bacteria. In this study, an efficient display system on Escherichia coli was developed using novel anchoring motifs designed from the E. coli mipA gene. Using the C-terminal fusion system of an industrial enzyme, Pseudomonas fluorescens lipase, six possible fusion sites, V140, V176, K179, V226, V232, and K234, which were truncated from the C-terminal end of the mipA gene (MV140, MV176, MV179, MV226, MV232, and MV234) were examined. The whole-cell lipase activities showed that MV140 was the best among the six anchoring motifs. Furthermore, the lipase activity obtained using MV140 as the anchoring motif was approximately 20-fold higher than that of the previous anchoring motifs FadL and OprF but slightly higher than that of YiaTR232. Western blotting and confocal microscopy further confirmed the localization of the fusion lipase displayed on the E. coli surface using the truncated MV140. Additionally the MV140 motif could be used for successfully displaying another industrial enzyme, α-amylase from Bacillus subtilis. These results showed that the fusion proteins using the MV140 motif had notably high enzyme activities and did not exert any adverse effects on either cell growth or outer membrane integrity. Thus, this study shows that MipA can be used as a novel anchoring motif for more efficient bacterial surface display in the biotechnological and industrial fields.

Outer membrane proteomics of kanamycin-resistant Escherichia coli identified MipA as a novel antibiotic resistance-related protein.

Antibiotic-resistant bacteria are a great threat to human health and food safety and there is an urgent need to understand the mechanisms of resistance for combating these bacteria. In the current study, comparative proteomic methodologies were applied to identify Escherichia coli K-12 outer membrane (OM) proteins related to kanamycin resistance. Mass spectrometry and western blotting results revealed that OM proteins TolC, Tsx and OstA were up-regulated, whereas MipA, OmpA, FadL and OmpW were down-regulated in kanamycin-resistant E. coli K-12 strain. Genetic deletion of tolC (ΔtolC-Km) led to a 2-fold decrease in the minimum inhibitory concentration (MIC) of kanamycin and deletion of mipA (ΔmipA-Km) resulted in a 4-fold increase in the MIC of kanamycin. Changes in the MICs for genetically modified strains could be completely recovered by gene complementation. Compared with the wild-type strain, the survival capability of ΔompA-Km was significantly increased and that of Δtsx-Km was significantly decreased. We further evaluated the role and expression of MipA in response to four other antibiotics including nalidixic acid, streptomycin, chloramphenicol and aureomycin, which suggested that MipA was a novel OM protein related to antibiotic resistance.