Reported xylazine exposure highly associated with overdose outcomes in a rapid community assessment among people who inject drugs in Baltimore.

BACKGROUND: Addressing xylazine harms are now a critical harm reduction priority, but relatively little epidemiological information exists to determine prevalence, magnitude, and correlates of xylazine use or related outcomes. METHODS: We conducted a rapid behavioral survey among people who inject drugs (n = 96) in Baltimore November-December 2022. Using a novel indicator of self-reported presumed xylazine effects, we examined prevalence and sociodemographic correlates of past year presumed xylazine effects and association with overdose and wound-related outcomes. Chi-square and descriptive statistics were used to examine bivariate associations overall and separately for those who reported xylazine by name and by reported fentanyl use frequency. RESULTS: Almost two-thirds (61.5%) reported experiencing xylazine effects. There were no differences by socio-demographics, but xylazine effects were more commonly reported among those who reported injecting alone (66% vs 38%%, p < 0.007) and daily fentanyl use (47% vs 24% p < 0.003). Those reporting xylazine exposure was three times as likely to report overdose (32% vs 11%, p < 0.03) and twice as likely to have used naloxone (78% vs 46%, p < 0.003). They also more commonly reported knowing someone who died of an overdose (92% vs 76%, p < 0.09) and to report an abscess requiring medical attention (36% vs 19%, p < 0.80). These associations were higher among respondents who specifically named xylazine and those who used fentanyl more frequently, but fentanyl frequency did not fully explain the heightened associations with xylazine effects. CONCLUSIONS: This study provides insight into the scope of xylazine exposure and associated health concerns among community-based PWID and suggests measures that may be instrumental for urgently needed research.

Injection Behaviors and Use of Syringe Service Programs over Time among People Who Inject Drugs in Baltimore, Maryland.

Introduction: People who inject drugs (PWID) are at increased risk for infectious disease transmission, including hepatitis C and HIV. Understanding trends in injection risk behaviors and syringe service program (SSP) use over time can help improve infectious disease prevention and other harm reduction services. Methods: Using National HIV Behavioral Surveillance System data from Baltimore, Maryland, we examined changes in receptive sharing of (1) syringes, (2) injection equipment, (3) syringes to divide drugs; and (4) receipt of syringes from SSPs among PWID from 2009 to 2018 (n = 518 in 2009, n = 638 in 2012, n = 586 in 2015, and n = 575 in 2018) using unadjusted and adjusted logistic models calculated across time for the total sample. Results: The conditional probability of receptive sharing of syringes and receipt of syringes from SSPs remained relatively stable, while receptive sharing of injection equipment and receptive sharing of syringes to divide drugs dropped substantially after 2009. White race and daily injection frequency were positively associated with sharing syringes and injection equipment and negatively associated with SSP use over time. In 2015, there was a notable shift such that women were twice as likely as men to receive syringes from SSPs and less likely than men to report the use of shared syringes or equipment. Conclusion: Findings indicate overall steady or decreasing trends in injection risk and steady trends in SSP usage over time, with some notable improvements among women and indications of shifting drug market patterns. Injection-related risk behaviors remain high among White PWID and may require targeted outreach and interventions.

Double-stranded RNA prevents and cures infection by rust fungi.

Fungal pathogens that impact perennial plants or natural ecosystems require management strategies beyond fungicides and breeding for resistance. Rust fungi, some of the most economically and environmentally important plant pathogens, have shown amenability to double-stranded RNA (dsRNA) mediated control. To date, dsRNA treatments have been applied prior to infection or together with the inoculum. Here we show that a dsRNA spray can effectively prevent and cure infection by Austropuccinia psidii (cause of myrtle rust) at different stages of the disease cycle. Significant reductions in disease coverage were observed in plants treated with dsRNA targeting essential fungal genes 48 h pre-infection through to 14 days post-infection. For curative treatments, improvements in plant health and photosynthetic capacity were seen 2-6 weeks post-infection. Two-photon microscopy suggests inhibitory activity of dsRNA on intercellular hyphae or haustoria. Our results show that dsRNA acts both preventively and curatively against myrtle rust disease, with treated plants recovering from severe infection. These findings have immediate potential in the management of the more than 10-year epidemic of myrtle rust in Australia.

RNA-Based Control of Fungal Pathogens in Plants.

Our duty to conserve global natural ecosystems is increasingly in conflict with our need to feed an expanding population. The use of conventional pesticides not only damages the environment and vulnerable biodiversity but can also still fail to prevent crop losses of 20-40% due to pests and pathogens. There is a growing call for more ecologically sustainable pathogen control measures. RNA-based biopesticides offer an eco-friendly alternative to the use of conventional fungicides for crop protection. The genetic modification (GM) of crops remains controversial in many countries, though expression of transgenes inducing pathogen-specific RNA interference (RNAi) has been proven effective against many agronomically important fungal pathogens. The topical application of pathogen-specific RNAi-inducing sprays is a more responsive, GM-free approach to conventional RNAi transgene-based crop protection. The specific targeting of essential pathogen genes, the development of RNAi-nanoparticle carrier spray formulations, and the possible structural modifications to the RNA molecules themselves are crucial to the success of this novel technology. Here, we outline the current understanding of gene silencing pathways in plants and fungi and summarize the pioneering and recent work exploring RNA-based biopesticides for crop protection against fungal pathogens, with a focus on spray-induced gene silencing (SIGS). Further, we discuss factors that could affect the success of RNA-based control strategies, including RNA uptake, stability, amplification, and movement within and between the plant host and pathogen, as well as the cost and design of RNA pesticides.

Exogenous double-stranded RNA inhibits the infection physiology of rust fungi to reduce symptoms in planta.

Rust fungi (Pucciniales) are a diverse group of plant pathogens in natural and agricultural systems. They pose ongoing threats to the diversity of native flora and cause annual crop yield losses. Agricultural rusts are predominantly managed with fungicides and breeding for resistance, but new control strategies are needed on non-agricultural plants and in fragile ecosystems. RNA interference (RNAi) induced by exogenous double-stranded RNA (dsRNA) has promise as a sustainable approach for managing plant-pathogenic fungi, including rust fungi. We investigated the mechanisms and impact of exogenous dsRNA on rust fungi through in vitro and whole-plant assays using two species as models, Austropuccinia psidii (the cause of myrtle rust) and Coleosporium plumeriae (the cause of frangipani rust). In vitro, dsRNA either associates externally or is internalized by urediniospores during the early stages of germination. The impact of dsRNA on rust infection architecture was examined on artificial leaf surfaces. dsRNA targeting predicted essential genes significantly reduced germination and inhibited development of infection structures, namely appressoria and penetration pegs. Exogenous dsRNA sprayed onto 1-year-old trees significantly reduced myrtle rust symptoms. Furthermore, we used comparative genomics to assess the wide-scale amenability of dsRNA to control rust fungi. We sequenced genomes of six species of rust fungi, including three new families (Araucariomyceaceae, Phragmidiaceae, and Skierkaceae) and identified key genes of the RNAi pathway across 15 species in eight families of Pucciniales. Together, these findings indicate that dsRNA targeting essential genes has potential for broad-use management of rust fungi across natural and agricultural systems.

BioClay™ prolongs RNA interference-mediated crop protection against Botrytis cinerea.

One of the most promising tools for the control of fungal plant diseases is spray-induced gene silencing (SIGS). In SIGS, small interfering RNA (siRNA) or double-stranded RNA (dsRNA) targeting essential or virulence-related pathogen genes are exogenously applied to plants and postharvest products to trigger RNA interference (RNAi) of the targeted genes, inhibiting fungal growth and disease. However, SIGS is limited by the unstable nature of RNA under environmental conditions. The use of layered double hydroxide or clay particles as carriers to deliver biologically active dsRNA, a formulation termed BioClay™, can enhance RNA durability on plants, prolonging its activity against pathogens. Here, we demonstrate that dsRNA delivered as BioClay can prolong protection against Botrytis cinerea, a major plant fungal pathogen, on tomato leaves and fruit and on mature chickpea plants. BioClay increased the protection window from 1 to 3 weeks on tomato leaves and from 5 to 10 days on tomato fruits, when compared with naked dsRNA. In flowering chickpea plants, BioClay provided prolonged protection for up to 4 weeks, covering the critical period of poding, whereas naked dsRNA provided limited protection. This research represents a major step forward for the adoption of SIGS as an eco-friendly alternative to traditional fungicides.

Wellbeing and Aging in The Australian Women's Weekly magazine.

This study investigates how the wellbeing trend in popular media regulates women's bodies and their selves through establishing norms around successful aging. We report on an exploratory qualitative content analysis of representations of wellbeing and aging from The Australian Women's Weekly (AWW) magazine. While some articles emphasized self-care and self-responsibility, many articulated relational and social/structural understandings of wellbeing. Compared with an earlier analysis of the AWW, our study found largely positive views of experiences of aging, associated with new opportunities and increased self-acceptance. These findings demonstrate how magazines both reflect and reinforce subtle processes of social change.

Contrasting epigenetic control of transgenes and endogenous genes promotes post-transcriptional transgene silencing in Arabidopsis.

Transgenes that are stably expressed in plant genomes over many generations could be assumed to behave epigenetically the same as endogenous genes. Here, we report that whereas the histone H3K9me2 demethylase IBM1, but not the histone H3K4me3 demethylase JMJ14, counteracts DNA methylation of Arabidopsis endogenous genes, JMJ14, but not IBM1, counteracts DNA methylation of expressed transgenes. Additionally, JMJ14-mediated specific attenuation of transgene DNA methylation enhances the production of aberrant RNAs that readily induce systemic post-transcriptional transgene silencing (PTGS). Thus, the JMJ14 chromatin modifying complex maintains expressed transgenes in a probationary state of susceptibility to PTGS, suggesting that the host plant genome does not immediately accept expressed transgenes as being epigenetically the same as endogenous genes.

Can-Seq: a PCR and DNA sequencing strategy for identifying new alleles of known and candidate genes.

BACKGROUND: Forward genetic screens are a powerful approach for identifying the genes contributing to a trait of interest. However, mutants arising in genes already known can obscure the identification of new genes contributing to the trait. Here, we describe a strategy called Candidate gene-Sequencing (Can-Seq) for rapidly identifying and filtering out mutants carrying new alleles of known and candidate genes. RESULTS: We carried out a forward genetic screen and identified 40 independent Arabidopsis mutants with defects in systemic spreading of RNA interference (RNAi), or more specifically in root-to-shoot transmission of post-transcriptional gene silencing (rtp). To classify the mutants as either representing a new allele of a known or candidate gene versus carrying a mutation in an undiscovered gene, bulk genomic DNA from up to 23 independent mutants was used as template to amplify a collection of 47 known or candidate genes. These amplified sequences were combined into Can-Seq libraries and deep sequenced. Subsequently, mutations in the known and candidate genes were identified using a custom Snakemake script (https://github.com/Carroll-Lab/can_seq), and PCR zygosity tests were then designed and used to identify the individual mutants carrying each mutation. Using this approach, we showed that 28 of the 40 rtp mutants carried homozygous nonsense, missense or splice site mutations in one or more of the 47 known or candidate genes. We conducted complementation tests to demonstrate that several of the candidate mutations were responsible for the rtp defect. Importantly, by exclusion, the Can-Seq pipeline also identified rtp mutants that did not carry a causative mutation in any of the 47 known and candidate genes, and these mutants represent an undiscovered gene(s) required for systemic RNAi. CONCLUSIONS: Can-Seq offers an accurate, cost-effective method for classifying new mutants into known versus unknown genes. It has several advantages over existing genetic and DNA sequencing approaches that are currently being used in forward genetic screens for gene discovery. Using Can-Seq in conjunction with map-based gene cloning is a cost-effective approach towards identifying the full complement of genes contributing to a trait of interest.

Optimization of a Multifrequency Magnetic Resonance Elastography Protocol for the Human Brain.

BACKGROUND AND PURPOSE: The brain's stiffness measurements from magnetic resonance elastography (MRE) strongly depend on actuation frequencies, which makes cross-study comparisons challenging. We performed a preliminary study to acquire optimal sets of actuation frequencies to accurately obtain rheological parameters for the whole brain (WB), white matter (WM), and gray matter (GM). METHODS: Six healthy volunteers aged between 26 and 72 years old went through MRE with a modified single-shot spin-echo echo planar imaging pulse sequence embedded with motion encoding gradients on a 3T scanner. Frequency-independent brain material properties and best-fit material model were determined from the frequency-dependent brain tissue response data (20 -80 Hz), by comparing four different linear viscoelastic material models (Maxwell, Kelvin-Voigt, Springpot, and Zener). During the material fitting, spatial averaging of complex shear moduli (G*) obtained under single actuation frequency was performed, and then rheological parameters were acquired. Since clinical scan time is limited, a combination of three actuation frequencies that would provide the most accurate approximation and lowest fitting error was determined for WB, WM, and GM by optimizing for the lowest Bayesian information criterion (BIC). RESULTS: BIC scores for the Zener and Springpot models showed these models approximate the multifrequency response of the tissue best. The best-fit frequency combinations for the reference Zener and Springpot models were identified to be 30-60-70 and 30-40-80 Hz, respectively, for the WB. CONCLUSIONS: Optimal sets of actuation frequencies to accurately obtain rheological parameters for WB, WM, and GM were determined from shear moduli measurements obtained via 3-dimensional direct inversion. We believe that our study is a first-step in developing a region-specific multifrequency MRE protocol for the human brain.

Cultivar and phosphorus effects on switchgrass yield and rhizosphere microbial diversity.

Switchgrass (Panicum virgatum L.) is a native perennial grass identified as a promising biofuel crop for production on marginal agricultural lands. As such, research into switchgrass fertility and the switchgrass rhizosphere microbiome has been ongoing in an effort to increase production sustainability. We examined the effects of cultivar and phosphorus (P) fertilization on biomass yield, P removal, and rhizosphere bacterial and fungal community structure in three switchgrass cultivars: Sunburst, Shawnee, and Liberty. The Liberty cv. is the first lowland-type bioenergy switchgrass adapted to USDA hardiness zones 4, 5, and 6. On a medium soil test P clay loam soil, biomass yield response to applied P was linear, increasing 135 kg ha-1 for every kilogram of P applied prior to establishment. Average post-frost biomass yield was 9.6 Mg ha-1 year-1 when unfertilized, and maximum biomass yield was 10.3 Mg ha-1 year-1 when fertilized at 58.6 kg ha-1 P, suggesting that P application on medium soil test P soils is beneficial for switchgrass establishment and early growth. Switchgrass cv. Shawnee was more productive than cvs. Liberty or Sunburst (11.3, 10.2, and 8.6 Mg ha-1 year-1, respectively). Both bacterial and fungal communities were significantly shaped by cultivar. These shifts, while inconsistent between year and cultivar, may reflect a selection of the microbial community from that present in soil to maximize total nutrient uptake, regardless of additional P amendments. Phosphorus fertilization did not affect microbial community structure. Results of this study suggest that the cultivar-associated selection of particular microbial taxa may have implications for increased productivity.

Flavodiiron-Mediated O2 Photoreduction Links H2 Production with CO2 Fixation during the Anaerobic Induction of Photosynthesis.

Some microalgae, such as Chlamydomonas reinhardtii, harbor a highly flexible photosynthetic apparatus capable of using different electron acceptors, including carbon dioxide (CO2), protons, or oxygen (O2), allowing survival in diverse habitats. During anaerobic induction of photosynthesis, molecular O2 is produced at photosystem II, while at the photosystem I acceptor side, the reduction of protons into hydrogen (H2) by the plastidial [FeFe]-hydrogenases primes CO2 fixation. Although the interaction between H2 production and CO2 fixation has been studied extensively, their interplay with O2 produced by photosynthesis has not been considered. By simultaneously measuring gas exchange and chlorophyll fluorescence, we identified an O2 photoreduction mechanism that functions during anaerobic dark-to-light transitions and demonstrate that flavodiiron proteins (Flvs) are the major players involved in light-dependent O2 uptake. We further show that Flv-mediated O2 uptake is critical for the rapid induction of CO2 fixation but is not involved in the creation of the micro-oxic niches proposed previously to protect the [FeFe]-hydrogenase from O2 By studying a mutant lacking both hydrogenases (HYDA1 and HYDA2) and both Flvs (FLVA and FLVB), we show that the induction of photosynthesis is strongly delayed in the absence of both sets of proteins. Based on these data, we propose that Flvs are involved in an important intracellular O2 recycling process, which acts as a relay between H2 production and CO2 fixation.

Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials.

BACKGROUND AND OBJECTIVE: Dysferlinopathies are a group of muscle disorders caused by mutations in the DYSF gene. Previous muscle imaging studies describe a selective pattern of muscle involvement in smaller patient cohorts, but a large imaging study across the entire spectrum of the dysferlinopathies had not been performed and previous imaging findings were not correlated with functional tests. METHODS: We present cross-sectional T1-weighted muscle MRI data from 182 patients with genetically confirmed dysferlinopathies. We have analysed the pattern of muscles involved in the disease using hierarchical analysis and presented it as heatmaps. Results of the MRI scans have been correlated with relevant functional tests for each region of the body analysed. RESULTS: In 181 of the 182 patients scanned, we observed muscle pathology on T1-weighted images, with the gastrocnemius medialis and the soleus being the most commonly affected muscles. A similar pattern of involvement was identified in most patients regardless of their clinical presentation. Increased muscle pathology on MRI correlated positively with disease duration and functional impairment. CONCLUSIONS: The information generated by this study is of high diagnostic value and important for clinical trial development. We have been able to describe a pattern that can be considered as characteristic of dysferlinopathy. We have defined the natural history of the disease from a radiological point of view. These results enabled the identification of the most relevant regions of interest for quantitative MRI in longitudinal studies, such as clinical trials. CLINICAL TRIAL REGISTRATION: NCT01676077.

A brief, trauma-informed intervention increases safety behavior and reduces HIV risk for drug-involved women who trade sex.

BACKGROUND: Female sex workers (FSWs) are an important population for HIV acquisition and transmission. Their risks are shaped by behavioral, sexual network, and structural level factors. Violence is pervasive and associated with HIV risk behavior and infection, yet interventions to address the dual epidemics of violence and HIV among FSWs are limited. METHODS: We used participatory methods to develop a brief, trauma-informed intervention, INSPIRE (Integrating Safety Promotion with HIV Risk Reduction), to improve safety and reduce HIV risk for FSWs. A quasi-experimental, single group pretest-posttest study evaluated intervention feasibility, acceptability and efficacy among FSWs in Baltimore, MD, most of whom were drug-involved (baseline n = 60; follow-up n = 39 [65%]; non-differential by demographics or outcomes). Qualitative data collected at follow-up contextualizes findings. RESULTS: Based on community partnership and FSW input, emergent goals included violence-related support, connection with services, and buffering against structural forces that blame FSWs for violence. Qualitative and quantitative results demonstrate feasibility and acceptability. At follow-up, improvements were seen in avoidance of client condom negotiation (p = 0.04), and frequency of sex trade under the influence of drugs or alcohol (p = 0.04). Women's safety behavior increased (p < 0.001). Participants improved knowledge and use of sexual violence support (p < 0.01) and use of intimate partner violence support (p < 0.01). By follow-up, most respondents (68.4%) knew at least one program to obtain assistance reporting violence to police. Over the short follow-up period, client violence increased. In reflecting on intervention acceptability, participants emphasized the value of a safe and supportive space to discuss violence. DISCUSSION: This brief, trauma-informed intervention was feasible and highly acceptable to FSWs. It prompted safety behavior, mitigated sex trade under the influence, and bolstered confidence in condom negotiation. INSPIRE influenced endpoints deemed valuable by community partners, specifically improving connection to support services and building confidence in the face of myths that falsely blame sex workers for violence. Violence persisted; prevention also requires targeting perpetrators, and longer follow-up durations as women acquire safety skills. This pilot study informs scalable interventions that address trauma and its impact on HIV acquisition and care trajectories for FSWs. CONCLUSION: Addressing violence in the context of HIV prevention is feasible, acceptable to FSWs, and can improve safety and reduce HIV risk, thus supporting FSW health and human rights.

Evolution of Chlamydomonas reinhardtii ferredoxins and their interactions with [FeFe]-hydrogenases.

Ferredoxins are soluble iron sulphur proteins which function as electron donors in a number of metabolic pathways in a broad range of organisms. In photosynthetic organisms, PETF, or ferredoxin 1 (FDX1), is the most studied ferredoxin due to its essential role in photosynthesis, where it transfers electrons from photosystem I to ferredoxin-NADP+ oxidoreductase. However, PETF can also transfer electrons to a large number of other proteins. One important PETF electron acceptor found in green microalgae is the biologically and biotechnologically important [FeFe]-hydrogenase HYDA, which catalyses the production of molecular hydrogen (H2) from protons and electrons. The interaction between PETF and HYDA is of considerable interest, as PETF is the primary electron donor to HYDA and electron supply is one of the main limiting factors for H2 production on a commercial scale. Although there is no three dimensional structure of the PETF-HYDA complex available, protein variants, nuclear magnetic resonance titration studies, molecular dynamics and modelling have provided considerable insight into the residues essential for forming and maintaining the interaction. In this review, we discuss the most recent findings with regard to ferredoxin-HYDA interactions and the evolution of the various Chlamydomonas reinhardtii ferredoxin isoforms. Finally, we provide an outlook on new PETF-based biotechnological approaches for improved H2 production efficiencies.

The structurally unique photosynthetic Chlorella variabilis NC64A hydrogenase does not interact with plant-type ferredoxins.

Hydrogenases from green algae are linked to the photosynthetic electron transfer chain via the plant-type ferredoxin PetF. In this work the [FeFe]-hydrogenase from the Trebouxiophycean alga Chlorella variabilis NC64A (CvHydA1), which in contrast to other green algal hydrogenases contains additional FeS-cluster binding domains, was purified and specific enzyme activities for both hydrogen (H2) production and H2 oxidation were determined. Interestingly, although C. variabilis NC64A, like many Chlorophycean algal strains, exhibited light-dependent H2 production activity upon sulfur deprivation, CvHydA1 did not interact in vitro with several plant-type [2Fe-2S]-ferredoxins, but only with a bacterial2[4Fe4S]-ferredoxin. In an electrochemical characterization, the enzyme exhibited features typical of bacterial [FeFe]-hydrogenases (e.g. minor anaerobic oxidative inactivation), as well as of algal enzymes (very high oxygen sensitivity).

Compartmentalisation of [FeFe]-hydrogenase maturation in Chlamydomonas reinhardtii.

Molecular hydrogen (H2 ) can be produced in green microalgae by [FeFe]-hydrogenases as a direct product of photosynthesis. The Chlamydomonas reinhardtii hydrogenase HYDA1 contains a catalytic site comprising a classic [4Fe4S] cluster linked to a unique 2Fe sub-cluster. From in vitro studies it appears that the [4Fe4S] cluster is incorporated first by the housekeeping FeS cluster assembly machinery, followed by the 2Fe sub-cluster, whose biosynthesis requires the specific maturases HYDEF and HYDG. To investigate the maturation process in vivo, we expressed HYDA1 from the C. reinhardtii chloroplast and nuclear genomes (with and without a chloroplast transit peptide) in a hydrogenase-deficient mutant strain, and examined the cellular enzymatic hydrogenase activity, as well as in vivo H2 production. The transformants expressing HYDA1 from the chloroplast genome displayed levels of H2 production comparable to the wild type, as did the transformants expressing full-length HYDA1 from the nuclear genome. In contrast, cells equipped with cytoplasm-targeted HYDA1 produced inactive enzyme, which could only be activated in vitro after reconstitution of the [4Fe4S] cluster. This indicates that the HYDA1 FeS cluster can only be built by the chloroplastic FeS cluster assembly machinery. Further, the expression of a bacterial hydrogenase gene, CPI, from the C. reinhardtii chloroplast genome resulted in H2 -producing strains, demonstrating that a hydrogenase with a very different structure can fulfil the role of HYDA1 in vivo and that overexpression of foreign hydrogenases in C. reinhardtii is possible. All chloroplast transformants were stable and no toxic effects were seen from HYDA1 or CPI expression.

Acceptability of microbicidal vaginal rings and oral pre-exposure prophylaxis for HIV prevention among female sex workers in a high-prevalence US city.

Biomedical HIV prevention tools including oral pre-exposure prophylaxis (PrEP) and vaginal microbicidal rings hold unique value for high-risk women who may have limited capacity for condom negotiation, including the key populations of sex workers and drug users. Commercial sex is a PrEP indicator in CDC guidelines, yet little is known about female sex workers' (FSWs) knowledge of and attitudes toward PrEP or the recently developed monthly vaginal microbicide rings. We describe knowledge and attitudes toward PrEP and microbicide rings in a sample of 60 mostly drug-using FSWs in Baltimore, Maryland, a high HIV-prevalence US city. Just 33% had heard of PrEP, but 65% were interested in taking daily oral PrEP and 76% were interested in a microbicide vaginal ring; 87% were interested in at least one of the two methods. Results suggest method mix will be important as biomedical tools for HIV prophylaxis are implemented and scaled up in this population, as 12% were interested in PrEP but not vaginal rings, while 19% were interested in vaginal rings but not in PrEP. Self-efficacy for daily oral adherence was high (79%) and 78% were interested in using PrEP even if condoms were still necessary. Women who had experienced recent client-perpetrated violence were significantly more interested in PrEP (86% vs 53%, p = 0.009) and microbicidal rings (91% vs 65%, p = 0.028) than women who had not recently experienced violence. No differences were observed by demographics nor HIV risk behaviors, suggesting broad potential interest in daily PrEP and monthly-use vaginal microbicides in this high-risk population.

Occupational Safety in the Age of the Opioid Crisis: Needle Stick Injury among Baltimore Police.

At a time of resurgence in injection drug use and injection-attributable infections, needle stick injury (NSI) risk and its correlates among police remain understudied. In the context of occupational safety training, a convenience sample of 771 Baltimore city police officers responded to a self-administered survey. Domains included NSI experience, protective behaviors, and attitudes towards syringe exchange programs. Sixty officers (8%) reported lifetime NSI. Officers identifying as Latino or other race were almost three times more likely (aOR 2.58, 95% CI 1.12-5.96) to have experienced NSI compared to whites, after adjusting for potential confounders. Findings highlight disparate burdens of NSIs among officers of color, elevating risk of hepatitis, HIV, and trauma. Training, equipment, and other measures to improve occupational safety are critical to attracting and safeguarding police, especially minority officers.

[FeFe]-Hydrogenase with Chalcogenide Substitutions at the H-Cluster Maintains Full H2 Evolution Activity.

The [FeFe]-hydrogenase HYDA1 from Chlamydomonas reinhardtii is particularly amenable to biochemical and biophysical characterization because the H-cluster in the active site is the only inorganic cofactor present. Herein, we present the complete chemical incorporation of the H-cluster into the HYDA1-apoprotein scaffold and, furthermore, the successful replacement of sulfur in the native [4FeH ] cluster with selenium. The crystal structure of the reconstituted pre-mature HYDA1[4Fe4Se]H protein was determined, and a catalytically intact artificial H-cluster variant was generated upon in vitro maturation. Full hydrogen evolution activity as well as native-like composition and behavior of the redesigned enzyme were verified through kinetic assays, FTIR spectroscopy, and X-ray structure analysis. These findings reveal that even a bioinorganic active site with exceptional complexity can exhibit a surprising level of compositional plasticity.