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BackgroundHydrogen sulfide is a highly toxic, flammable, and colorless gas. Hydrogen sulfide has been identified as a potential terrorist chemical threat agent in mass-casualty events. Our previous studies showed that cobinamide, a vitamin B12 analog, effectively reverses the toxicity from hydrogen sulfide poisoning. In this study, we investigate the effectiveness of intratracheally administered cobinamide in treating a lethal dose hydrogen sulfide gas inhalation and compare its performance to saline control administration.MethodsA total of 53 pathogen-free New Zealand White rabbits were used for this study. Four groups were compared: (i) received no saline solution or drug intratracheally (n = 15), (ii) slow drip saline intratracheally (n = 15), (iii) fast drip saline intratracheally (n = 15), and (iv) slow drip cobinamide intratracheally (n = 8). Blood pressure was continuously monitored, and deoxy- and oxyhemoglobin concentration changes were monitored in real-time in vivo using continuous wave near-infrared spectroscopy.ResultsThe mean (± standard deviation) weight for all animals (n = 53) was 3.87 ± 0.10 kg. The survival rates of the slow cobinamide and the fast saline groups were 75 percent and 60 percent, respectively, while the survival rates in the slow saline and control groups were 26.7 percent and 20 percent, respectively. A log-rank (Mantel-Cox) test showed that survival in fast saline and slow cobinamide groups were significantly greater than those of no saline control and slow saline groups (P

BACKGROUND: Protection against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]) can limit transmission and the risk of post-COVID conditions, and is particularly important among healthcare personnel. However, lower vaccine effectiveness (VE) has been reported since predominance of the Omicron SARS-CoV-2 variant. METHODS: We evaluated the VE of a monovalent messenger RNA (mRNA) booster dose against COVID-19 from October 2021 to June 2022 among US healthcare personnel. After matching case-participants with COVID-19 to control-participants by 2-week period and site, we used conditional logistic regression to estimate the VE of a booster dose compared with completing only 2 mRNA doses >150 days previously, adjusted for multiple covariates. RESULTS: Among 3279 case-participants and 3998 control-participants who had completed 2 mRNA doses, we estimated that the VE of a booster dose against COVID-19 declined from 86% (95% confidence interval, 81%-90%) during Delta predominance to 65% (58%-70%) during Omicron predominance. During Omicron predominance, VE declined from 73% (95% confidence interval, 67%-79%) 14-60 days after the booster dose, to 32% (4%-52%) ≥120 days after a booster dose. We found that VE was similar by age group, presence of underlying health conditions, and pregnancy status on the test date, as well as among immunocompromised participants. CONCLUSIONS: A booster dose conferred substantial protection against COVID-19 among healthcare personnel. However, VE was lower during Omicron predominance, and waning effectiveness was observed 4 months after booster dose receipt during this period. Our findings support recommendations to stay up to date on recommended doses of COVID-19 vaccines for all those eligible.

In Trypanosoma brucei, the editosome, composed of RNA-editing substrate-binding complex (RESC) and RNA-editing catalytic complex (RECC), orchestrates guide RNA (gRNA)-programmed editing to recode cryptic mitochondrial transcripts into messenger RNAs (mRNAs). The mechanism of information transfer from gRNA to mRNA is unclear owing to a lack of high-resolution structures for these complexes. With cryo-electron microscopy and functional studies, we have captured gRNA-stabilizing RESC-A and gRNA-mRNA-binding RESC-B and RESC-C particles. RESC-A sequesters gRNA termini, thus promoting hairpin formation and blocking mRNA access. The conversion of RESC-A into RESC-B or -C unfolds gRNA and allows mRNA selection. The ensuing gRNA-mRNA duplex protrudes from RESC-B, likely exposing editing sites to RECC-catalyzed cleavage, uridine insertion or deletion, and ligation. Our work reveals a remodeling event facilitating gRNA-mRNA hybridization and assembly of a macromolecular substrate for the editosome's catalytic modality.

3-methylcrotonyl-CoA carboxylase (MCC) is a biotin-dependent mitochondrial enzyme necessary for leucine catabolism in most organisms. While the crystal structure of recombinant bacterial MCC has been characterized, the structure and potential polymerization of native MCC remain elusive. Here, we discovered that native MCC from Leishmania tarentolae (LtMCC) forms filaments, and determined the structures of different filament regions at 3.4, 3.9, and 7.3 Å resolution using cryoEM. α6β6 LtMCCs assemble in a twisted-stacks architecture, manifesting as supramolecular rods up to 400 nm. Filamentous LtMCCs bind biotin non-covalently and lack coenzyme A. Filaments elongate by stacking α6β6 LtMCCs onto the exterior α-trimer of the terminal LtMCC. This stacking immobilizes the biotin carboxylase domains, sequestering the enzyme in an inactive state. Our results support a new model for LtMCC catalysis, termed the dual-swinging-domains model, and cast new light on the function of polymerization in the carboxylase superfamily and beyond.

Open space, defined as any open piece of land that is undeveloped, and is accessible to the public, may be particularly beneficial to seniors (defined as those aged 65+), who are often at high risk of social isolation and deteriorating physical and mental health. Despite documented benefits, seniors remain one of the most underserved groups in terms of physical activity and open space use, with opportunities being limited even further due to the COVID-19 pandemic. This report seeks to explore seniors’ preferences for the design of open spaces that fulfill their physical activity and other social needs in the communities of Rowland Heights and Hacienda Heights. Methods used to obtain data included surveys, site visits to major open spaces, and digital scans of online data about public park usage during the pandemic. The findings revealed open spaces in these areas being hard to navigate on foot, parks conceived as central “pandemic” meeting places, and a high demand for open spaces in neighborhoods distant from parks. The final recommendations provide ways to transform nontraditional open spaces, defined as areas not typically utilized as open spaces, such as vacant lots and parklets, using affordable and senior-friendly elements. Specifically, findings are made replicable across different neighborhoods in the East San Gabriel Valley through 6 general themes that translate into actionable constructs: Control, Safety, Access, Social Support, Biophilic Design, Active Recreation. By providing a guideline to designing open spaces in underutilized areas within a budget, the goal is that there will be greater leverage towards creating nontraditional open spaces.

Intuitive metacognitive processes such as metaperception surprisingly have a lot moreinfluence on the intersectionality between interpersonal relations and health than one thinks. Of the many forms of metaperception, this paper aims to further explore the overblown implications effect (OIE), which is a prevalent metaperception error where one overestimates how much other people think of their successes or failures. We conducted a mixed ANOVA analysis and found further support for the statistically significant discrepancy between actors’ metaperception ratings and observers’ social perception ratings. For the extension, we continue to explore whether a longer rating duration for the actors would result in more accurate predictions of observers’ ratings compared to observers’ actual ratings by running a mixed ANOVA analysis. We hypothesized that increasing the rating duration would decrease the difference between the actors’ metaperception ratings and the observers’ social perception ratings, but our results show that there is no statistical significance between the two variables. However, it is important to note that we could not use the whole data provided due to statistical limitations. Hence, this makes it even more essential that future studies work with more representative samples to further understand the correlative factors that influence the OIE.

Optogenetic effectors and sensors provide a novel real-time window into complex physiological processes, enabling determination of molecular signaling processes within functioning cellular networks. However, the combination of these optical tools in mice is made practical by construction of genetic lines that are optically compatible and genetically tractable. We present a new toolbox of 21 mouse lines with lineage-specific expression of optogenetic effectors and sensors for direct biallelic combination, avoiding the multiallelic requirement of Cre recombinase -mediated DNA recombination, focusing on models relevant for cardiovascular biology. Optogenetic effectors (11 lines) or Ca2+ sensors (10 lines) were selectively expressed in cardiac pacemaker cells, cardiomyocytes, vascular endothelial and smooth muscle cells, alveolar epithelial cells, lymphocytes, glia, and other cell types. Optogenetic effector and sensor function was demonstrated in numerous tissues. Arterial/arteriolar tone was modulated by optical activation of the second messengers InsP3 (optoα1AR) and cAMP (optoß2AR), or Ca2+-permeant membrane channels (CatCh2) in smooth muscle (Acta2) and endothelium (Cdh5). Cardiac activation was separately controlled through activation of nodal/conducting cells or cardiac myocytes. We demonstrate combined effector and sensor function in biallelic mouse crosses: optical cardiac pacing and simultaneous cardiomyocyte Ca2+ imaging in Hcn4BAC-CatCh2/Myh6-GCaMP8 crosses. These experiments highlight the potential of these mice to explore cellular signaling in vivo, in complex tissue networks.

This paper details a theoretical research proposal to explore the efficacy of theevent-related potential (ERP) component P300 as a potential biomarker in the early detection of Alzheimer’s disease. To determine P300’s efficacy as a biomarker, an electroencephalogram test, which monitors and generates data on the electrical activity of the brain via scalp electrodes, and an auditory oddball test, which aims to assess the cognitive functioning of participants, were performed. The auditory oddball test involved playing a series of tones of two different frequencies (one is the standard tone, and the other is the target tone) for participants and having participants press a button whenever they heard a target tone. Accuracy and reaction time were recorded. The aforementioned two tests depicted a strong association between P300 and the cognitive decline of patients with Alzheimer’s Disease (AD), suggesting that this ERP component may be used for the early detection of AD, which may improve the efficacy of future treatment and the overall quality of life for diagnosed patients in the long run.

Despite the growth of the Maker Movement, few studies have examined what learning opportunities in teacher education programs facilitate preservice teachers' understanding of inclusive making for students from diverse backgrounds. This study explored how preservice teachers used their funds of knowledge for making projects in a STEM education course and how the use of these funds of knowledge influenced their perspectives on maker education. Guided by ethnographic research principles, we analyzed qualitative data collected from 15 preservice teachers. The findings show that preservice teachers used their diverse funds of knowledge in ways that: (a) transformed making practices into personally relevant learning activities, (b) positioned themselves as experts, (c) facilitated mutual learning, and (d) provided a significant resource for creative ideas in advancing making projects.

Different immigrant generations may encounter distinct sexual opportunities with implications for HIV transmission. Yet, few studies have examined how immigrant generational status is associated with sexual risk behaviors among men who have sex with men (MSM). We explored relationships between immigrant generational status, social support, and sexual risk behaviors among English-speaking MSM using data from surveys conducted in Seattle, Washington, in 2014 (n = 323). We compared the sexual risk behaviors and social support of first-generation, second-generation, and third- and higher-generation MSM, and examined whether immigrant generational status and social support were associated with sexual risk behaviors using logistic regression models. Second-generation MSM reported lower friend social support than first- or third- and higher-generation MSM (p < .05). However, immigrant generational status was not associated with sexual risk behavior outcomes, even after accounting for social support. Results suggest that differences in immigration processes such as acculturation may be more predictive of risk behaviors than generational status alone.

The internet has become the chosen medium for professional learning. Completing professional learning can improve work performance; however, many individuals who begin online courses do not complete them. It is not well understood which influences keep individuals engaged in online professional learning. We address these issues with a systematic review. Our review of 51 studies and 9,583 participants includes a narrative synthesis and a meta-analysis that examined influences on user engagement in online professional learning. We found that course design and employers' provision of time to complete learning are key for engaging learners. Other important influences were learners' reasons for learning (e.g., intrinsic value and perceived usefulness), access to learning support, and opportunities for interaction during the learning experience.