Abstract
Background
The secondary impacts of the COVID-19 pandemic may disproportionately affect gay, bisexual, and other men who have sex with men (GBM), particularly related to HIV prevention and ...treatment outcomes. We applied syndemic theory to examine PrEP disruptions during the during the height of the COVID-19 pandemic in Vancouver, Canada.
Methods
Sexually-active GBM, aged 16 + years, were enrolled through respondent-driven sampling (RDS) from February 2017 to August 2019. Participants completed a Computer-Assisted Self-Interview every six months and data were linked to the BC PrEP Program (program responsible for publicly funded PrEP in the province) to directly measure PrEP disruptions. The analysis period for this study was from March 2018-April 2021. We used univariable generalized linear mixed models to examine (1) six-month trends for syndemic conditions: the prevalence of moderate/severe depressive or anxiety symptoms, polysubstance use, harmful alcohol consumption, intimate partner violence, and (2) six-month trends for PrEP interruptions among HIV-negative/unknown GBM. We also applied 3-level mixed-effects logistic regression with RDS clustering to examine whether syndemic factors were associated with PrEP interruptions.
Results
Our study included 766 participants, with 593 participants who had at least one follow-up visit. The proportion of respondents with abnormal depressive symptoms increased over the study period (OR = 1.35; 95%CI = 1.17, 1.56), but we found decreased prevalence for polysubstance use (OR = 0.89; 95%CI = 0.82, 0.97) and binge drinking (OR = 0.74; 95%CI = 0.67, 0.81). We also found an increase in PrEP interruptions (OR = 2.33; 95%CI = 1.85, 2.94). GBM with moderate/severe depressive symptoms had higher odds (aOR = 4.80; 95%CI = 1.43, 16.16) of PrEP interruptions, while GBM with experiences of IPV had lower odds (aOR = 0.38; 95%CI = 0.15, 0.95) of PrEP interruptions. GBM who met clinical eligibility for PrEP had lower odds of experiencing PrEP interruptions (aOR = 0.25; 95%CI = 0.11, 0.60).
Conclusion
There were increasing PrEP interruptions since March 2020. However, those most at risk for HIV were less likely to have interruptions. Additional mental health services and targeted follow-up for PrEP continuation may help to mitigate the impacts of the COVID-19 pandemic on GBM.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Two high-spin Fe(II) and Co(II) complexes of 1,4,7,10-tetraazacyclododecane (CYCLEN) appended with four 2-amino-6-picolyl groups, denoted as Fe(TAPC)2+ and Co(TAPC)2+, are reported. These ...complexes demonstrate C 2-symmetrical geometry from coordination of two pendents, and they are present in a single diastereomeric form in aqueous solution as shown by 1H NMR spectroscopy and by a single-crystal X-ray structure for the Co(II) complex. A highly shifted but low-intensity CEST (chemical exchange saturation transfer) signal from NH groups is observed at −118 ppm for Co(TAPC)2+ at pH 6.0 and 37 °C. A higher intensity CEST peak is observed for Fe(TAPC)2+, which demonstrates a pH-dependent frequency shift from −72 to −79 ppm at pH 7.7 to 4.8, respectively, at 37 °C. This shift in the CEST peak correlates with the protonation of the unbound 2-amino-6-picolyl pendents, as suggested by UV–vis and 1H NMR spectroscopy studies at different pH values. Phantom imaging demonstrates the challenges and feasibility of using the Fe(TAPC)2+ agent on a low-field MRI scanner. The Fe(TAPC)2+ complex is the first transition-metal-based paraCEST agent that produces a pH-induced CEST frequency change toward the development of probes for concentration-independent imaging of pH.
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IJS, KILJ, NUK, PNG, UL, UM
Aberrant lipid metabolism promotes the development of skeletal muscle insulin resistance, but the exact identity of lipid-mediated mechanisms relevant to human obesity remains unclear. A ...comprehensive lipidomic analysis of primary myocytes from individuals who were insulin-sensitive and lean (LN) or insulin-resistant with obesity (OB) revealed several species of lysophospholipids (lyso-PLs) that were differentially abundant. These changes coincided with greater expression of lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme involved in phospholipid transacylation (Lands cycle). Strikingly, mice with skeletal muscle-specific knockout of LPCAT3 (LPCAT3-MKO) exhibited greater muscle lysophosphatidylcholine/phosphatidylcholine, concomitant with improved skeletal muscle insulin sensitivity. Conversely, skeletal muscle-specific overexpression of LPCAT3 (LPCAT3-MKI) promoted glucose intolerance. The absence of LPCAT3 reduced phospholipid packing of cellular membranes and increased plasma membrane lipid clustering, suggesting that LPCAT3 affects insulin receptor phosphorylation by modulating plasma membrane lipid organization. In conclusion, obesity accelerates the skeletal muscle Lands cycle, whose consequence might induce the disruption of plasma membrane organization that suppresses muscle insulin action.
Several paramagnetic Co(II) and Fe(II) macrocyclic complexes were prepared with the goal of introducing a bound water ligand to produce paramagnetically shifted water 1H resonances and for ...paramagnetic chemical exchange saturation transfer (paraCEST) applications. Three 12-membered macrocycles with amide pendent groups including 1,7-bis(carbamoylmethyl)-1,4,7,10-tetraazacyclodocane (DCMC), 4,7,10-tris(carbamoylmethyl)-,4,7,10-triaza-12-crown-ether (N3OA), and 4,10-bis(carbamoylmethyl)-4,10-diaza-12-crown-ether (NODA) were prepared and their Co(II) complexes were characterized in the solid state and in solution. The crystal structure of Co(DCMC)Br2 featured a six-coordinated Co(II) center with distorted octahedral geometry, while Co(NODA)(OH2)Cl2 and Co(N3OA)(NO3)2 were seven-coordinated. The analogous Fe(II) complexes of NODA and NO3A were successfully prepared, but the complex of DCMC oxidized rapidly to the Fe(III) form. Similarly, Fe(NODA)2+ oxidized over several days, forming crystals of the Fe(III) complex isolated as the μ-O bridged dimer. Magnetic susceptibility values and paramagnetic NMR spectra of the Fe(II) complexes of NODA and N3OA, as well as Co(II) complexes of DCMC, NODA, and N3OA, were consistent with high spin complexes. CEST peaks ranging from 60 ppm to 70 ppm, attributed to NH groups of the amide pendents, were identified. Variable-temperature 17O NMR spectra of Co(II) and Fe(II) NODA complexes were consistent with rapid exchange of the water ligand with bulk water. Notably, the Co(II) and Fe(II) complexes presented here produced substantial paramagnetic shifts of bulk water 1H resonances, independent of having an inner-sphere water.
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IJS, KILJ, NUK, PNG, UL, UM
This study evaluated the association between resilience and PrEP use among a population-based sample of Canadian gay, bisexual, and other men who have sex with men (GBM). Sexually active GBM aged ≥ ...16 years old were recruited via respondent-driven sampling (RDS) in Toronto, Montreal, and Vancouver from 02/2017 to 07/2019. We conducted a pooled cross-sectional analysis of HIV-negative/unknown GBM who met clinical eligibility for PrEP. We performed multivariable RDS-II-weighted logistic regression to assess the association between scores on the Connor-Davidson Resilience-2 Scale and PrEP. Mediation analyses with weighted logistic and linear regression were used to assess whether the relationship between minority stressors and PrEP use was mediated by resilience. Of 1167 PrEP-eligible GBM, 317 (27%) indicated they took PrEP in the past six months. Our multivariable model found higher resilience scores were associated with greater odds of PrEP use in the past six months (aOR = 1.13, 95%CI = 1.00, 1.28). We found that resilience reduced the effect of the association between heterosexist discrimination and PrEP use. Resilience also mediated the relationship between internalized homonegativity and PrEP use and mediated the effect of the association between LGBI acceptance concern and PrEP use. Overall, PrEP-eligible GBM with higher resilience scores had a greater odds of PrEP use in the past six months. We also found mixed results for the mediating role of resilience between minority stress and PrEP use. These findings underline the continued importance of strength-based factors in HIV prevention.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Photo-responsive metal–organic frameworks (MOFs) are one example of light controlled smart materials for use in advanced sensors, data storage, actuators and molecular switches. Herein we show the ...design, synthesis and characterization of a photo-responsive linker that is subsequently reacted to yield MOF single crystals. The photo-responsive properties of the resulting UBMOF-2 arise from the photo-induced cyclization of the diarylethene moiety designed into the linker. Computational modeling to assess the relative energies of linker atropisomers reveals a large energetic barrier preventing facile interconversion between key species. The role of this barrier on the observed photo-induced fatigue provides useful insight into the development of advanced photo-responsive nanoporous materials.
Obesity alters skeletal muscle lipidome and promotes myopathy, but it is unknown whether aberrant muscle lipidome contributes to the reduction in skeletal muscle contractile force‐generating ...capacity. Comprehensive lipidomic analyses of mouse skeletal muscle revealed a very strong positive correlation between the abundance of lysophosphatidylcholine (lyso‐PC), a class of lipids that is known to be downregulated with obesity, with maximal tetanic force production. The level of lyso‐PC is regulated primarily by lyso‐PC acyltransferase 3 (LPCAT3), which acylates lyso‐PC to form phosphatidylcholine. Tamoxifen‐inducible skeletal muscle‐specific overexpression of LPCAT3 (LPCAT3‐MKI) was sufficient to reduce muscle lyso‐PC content in both standard chow diet‐ and high‐fat diet (HFD)‐fed conditions. Strikingly, the assessment of skeletal muscle force‐generating capacity ex vivo revealed that muscles from LPCAT3‐MKI mice were weaker regardless of diet. Defects in force production were more apparent in HFD‐fed condition, where tetanic force production was 40% lower in muscles from LPCAT3‐MKI compared to that of control mice. These observations were partly explained by reductions in the cross‐sectional area in type IIa and IIx fibers, and signs of muscle edema in the absence of fibrosis. Future studies will pursue the mechanism by which LPCAT3 may alter protein turnover to promote myopathy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The discovery of the conductivity of polyacetylene ignited the field of organic electronic materials. Functionalizing polyacetylenes with electron withdrawing groups (
e.g.
, fluorine), has been ...predicted to increase the air-stability of PAs and open new avenues in organic electronics. Burns and coworkers recently reported a novel synthetic route to fluorinated polyacetylenes which utilizes as a key step towards the stereoselective photochemical electrocyclic ring-closing of hexafluorinated dienes. We call this selectivity, photo-torquoselectivity. While Houk's torquoselectivity model predicts the stereoselectivity of thermal electrocyclic reactions, no such reactivity model exists for their photochemical counterpart. We have used multiconfigurational quantum chemical calculations and
ab initio
molecular dynamics simulations to describe this reaction and to determine the origin of its stereoselectivity. We show that the reaction proceeds through the S
1
excited state with a half-life of 445 fs. This reaction lies along an energetically unfavorable pathway which results in a reaction quantum yield of approximately 14%. We predict that the reaction pathway to the unobserved product lies as much as 0.3 eV (6.9 kcal mol
−1
) higher in energy than the pathway to the observed isomer. The reaction pathway to the observed product benefits from stabilizing F
δ
−
H
δ
+
interactions while the pathway to the unobserved product suffers from destabilizing F-F closed-shell repulsion. The combination of these two stereoelectronic effects is responsible for the difference in energy between the two pathways which directs the reaction exclusively to the observed product.
We determined the origin of a photo-torquoselective 4π-electrocyclic ring closing of hexafluoro-5-ladderene with multiconfigurational calculations and nonadiabatic dynamics simulations (256 1 ps CASSCF(6,7)/ANO-S-VDZP trajectories).
Objective: Supportive social relationships can have direct positive effects on health and mitigate the negative impact of stressors. This study investigated the main effect of perceived social ...support on STI/HIV risk and prevention behaviors. The buffering effect of perceived social support on the impact of proximal minority stressors, like internalized homonegativity, was also examined on one risk behavior specifically, condomless anal sex (CAS) without HIV preexposure prophylaxis (PrEP) use. Method: HIV-negative gay, bisexual, and other men who have sex with men (GBM) were recruited using respondent driven sampling from three major Canadian urban centers (n = 1,409). GBM completed measures of perceived social support, proximal minority stress, and engagement in STI/HIV risk and prevention behaviors. Results: Higher perceived social support was positively associated with a several health behaviors, including recent STI and HIV testing, discussing HIV status with prospective partners, the use of behavioral HIV-risk reduction strategies during sexual encounters, and a lower likelihood of engaging in CAS without PrEP. There was evidence of moderation as well. Among GBM with higher perceived social support, internalized homonegativity was no longer associated with increased odds of engaging in CAS without PrEP. Conclusions: The results of the current study advance social support theory to GBM in the context of biomedical prevention, showing both evidence of both direct associations and buffering effects on STI/HIV risk and prevention behaviors. This highlights the importance of promoting social support seeking in interventions aimed at improving GBM health.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Reactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which ...downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here, we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacological neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediates age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacological suppression.
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