6 research outputs found
Measuring Population Transmission Potential for HIV: An Alternative Metric of Transmission Risk in Men who have Sex with Men (MSM) in the US
Background Various metrics for HIV burden and treatment success [e.g. HIV prevalence, community viral load (CVL), population viral load (PVL), percent of HIV-positive persons with undetectable viral load] have important public health limitations for understanding disparities. Methods and Findings Using data from an ongoing HIV incidence cohort of black and white men who have sex with men (MSM), we propose a new metric to measure the prevalence of those at risk of transmitting HIV and illustrate its value. âŠSee full text for complete abstract
Biogenesis of JC Polyomavirus Associated Extracellular Vesicles
JC polyomavirus (JCPyV) is a small, non-enveloped virus that persists in the kidney in about half the adult population. In severely immune-compromised individuals JCPyV causes the neurodegenerative disease progressive multifocal leukoencephalopathy (PML) in the brain. JCPyV has been shown to infect cells by both direct and indirect mechanisms, the latter involving extracellular vesicle (EV) mediated infection. While direct mechanisms of infection are well studied indirect EV mediated mechanisms are poorly understood. Using a combination of chemical and genetic approaches we show that several overlapping intracellular pathways are responsible for the biogenesis of virus containing EV. Here we show that targeting neutral sphingomyelinase 2 (nSMase2) with the drug cambinol decreased the spread of JCPyV over several viral life cycles. Genetic depletion of nSMase2 by either shRNA or CRISPR/Cas9 reduced EV-mediated infection. Individual knockdown of seven ESCRT-related proteins including HGS, ALIX, TSG101, VPS25, VPS20, CHMP4A, and VPS4A did not significantly reduce JCPyV associated EV (JCPyV(+) EV) infectivity, whereas knockdown of the tetraspanins CD9 and CD81 or trafficking and/or secretory autophagy-related proteins RAB8A, RAB27A, and GRASP65 all significantly reduced the spread of JCPyV and decreased EV-mediated infection. These findings point to a role for exosomes and secretory autophagosomes in the biogenesis of JCPyV associated EVs with specific roles for nSMase2, CD9, CD81, RAB8A, RAB27A, and GRASP65 proteins
Lack of Awareness of Human Immunodeficiency Virus (HIV) Infection: Problems and Solutions With Self-reported HIV Serostatus of Men Who Have Sex With Men
Background. Lack of human immunodeficiency virus (HIV) infection awareness may be a driver of racial disparities in HIV infection amongmen who have sex withmen (MSM). Lack of awareness is typicallymeasured by comparing HIV test result to self-reported HIV status. This measure may be subject to reporting bias and alternatives are needed. Methods. The InvolveMENt study examined HIV disparities between black and whiteMSM from Atlanta. Among HIV-positive participants who did not report knowing they were positive, we examined other measures of awareness: HIV viral load (VL)/mL (low VL), antiretroviral (ARV) drugs in blood, and previous HIV case surveillance report. Results. Using self-report only, 32% (62 of 192) of black and 16% (7 of 45) of white MSM were not aware of their HIV infection (P = .03). Using self-report and low VL, 25% (48 of 192) black and 16% (7 of 45) white MSM lacked awareness (P = .18). Using self-report and ARVs, 26% (50 of 192) black and 16% (7 of 45) white MSM lacked awareness (P = .14). Using self-report and surveillance report, 15% (28 of 192) black and 13% (6 of 45) white MSM lacked awareness (P = .83). Conclusions. Self-report only may overestimate true lack of awareness of HIV status for black MSM. If, as our data suggest, black MSM are not less likely to be aware of their HIV infection than are white MSM, then this factor is not a substantial driver of HIV disparity. Future HIV research that depends on accuratemeasurement of HIV status awareness should consider including additional laboratory and case surveillance data
TRY plant trait database â enhanced coverage and open access
Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of traitâbased plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for âplant growth formâ. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and traitâenvironmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives
Is the timing of fixation associated with fracture-related infection among tibial plateau fracture patients with compartment syndrome? A multicenter retrospective cohort study of 729 patients.
BACKGROUND: Tibial plateau fractures with an ipsilateral compartment syndrome are a clinical challenge with limited guidance regarding the best time to perform open reduction and internal fixation (ORIF) relative to fasciotomy wound closure. This study aimed to determine if the risk of fracture-related infection (FRI) differs based on the timing of tibial plateau ORIF relative to closure of ipsilateral fasciotomy wounds.
METHODS: A retrospective cohort study identified patients with tibial plateau fractures and an ipsilateral compartment syndrome treated with 4-compartment fasciotomy at 22 US trauma centers from 2009 to 2019. The primary outcome measure was FRI requiring operative debridement after ORIF. The ORIF timing relative to fasciotomy closure was categorized as ORIF before, at the same time as, or after fasciotomy closure. Bayesian hierarchical regression models with a neutral prior were used to determine the association between timing of ORIF and infection. The posterior probability of treatment benefit for ORIF was also determined for the three timings of ORIF relative to fasciotomy closure.
RESULTS: Of the 729 patients who underwent ORIF of their tibial plateau fracture, 143 (19.6%) subsequently developed a FRI requiring operative treatment. Patients sustaining infections were: 21.0% of those with ORIF before (43 of 205), 15.9% at the same time as (37 of 232), and 21.6% after fasciotomy wound closure (63 of 292). ORIF at the same time as fasciotomy closure demonstrated a 91% probability of being superior to before closure (RR, 0.75; 95% CrI, 0.38 to 1.10). ORIF after fasciotomy closure had a lower likelihood (45%) of a superior outcome than before closure (RR, 1.02; 95% CrI; 0.64 to 1.39).
CONCLUSION: Data from this multicenter cohort confirms previous reports of a high FRI risk in patients with a tibial plateau fracture and ipsilateral compartment syndrome. Our results suggest that ORIF at the time of fasciotomy closure has the highest probability of treatment benefit, but that infection was common with all three timings of ORIF in this difficult clinical situation
Is the timing of fixation associated with fracture-related infection among tibial plateau fracture patients with compartment syndrome? A multicenter retrospective cohort study of 729 patients.
BACKGROUND: Tibial plateau fractures with an ipsilateral compartment syndrome are a clinical challenge with limited guidance regarding the best time to perform open reduction and internal fixation (ORIF) relative to fasciotomy wound closure. This study aimed to determine if the risk of fracture-related infection (FRI) differs based on the timing of tibial plateau ORIF relative to closure of ipsilateral fasciotomy wounds.
METHODS: A retrospective cohort study identified patients with tibial plateau fractures and an ipsilateral compartment syndrome treated with 4-compartment fasciotomy at 22 US trauma centers from 2009 to 2019. The primary outcome measure was FRI requiring operative debridement after ORIF. The ORIF timing relative to fasciotomy closure was categorized as ORIF before, at the same time as, or after fasciotomy closure. Bayesian hierarchical regression models with a neutral prior were used to determine the association between timing of ORIF and infection. The posterior probability of treatment benefit for ORIF was also determined for the three timings of ORIF relative to fasciotomy closure.
RESULTS: Of the 729 patients who underwent ORIF of their tibial plateau fracture, 143 (19.6%) subsequently developed a FRI requiring operative treatment. Patients sustaining infections were: 21.0% of those with ORIF before (43 of 205), 15.9% at the same time as (37 of 232), and 21.6% after fasciotomy wound closure (63 of 292). ORIF at the same time as fasciotomy closure demonstrated a 91% probability of being superior to before closure (RR, 0.75; 95% CrI, 0.38 to 1.10). ORIF after fasciotomy closure had a lower likelihood (45%) of a superior outcome than before closure (RR, 1.02; 95% CrI; 0.64 to 1.39).
CONCLUSION: Data from this multicenter cohort confirms previous reports of a high FRI risk in patients with a tibial plateau fracture and ipsilateral compartment syndrome. Our results suggest that ORIF at the time of fasciotomy closure has the highest probability of treatment benefit, but that infection was common with all three timings of ORIF in this difficult clinical situation