Young adults have the highest cumulative incidence of COVID-19 infection in the country. Using March 2021 Household Pulse Survey data, an ongoing, cross-sectional nationally representative survey, we ...examined U.S. young adult intention to accept COVID-19 vaccines.
Young adult (ages 18–25 years) Household Pulse Survey participants were queried on intention to receive a COVID-19 vaccine and related perspectives (N = 5,082).
Most unvaccinated respondents (76%) indicated an intention to become vaccinated. The most frequently cited reasons for potentially rejecting vaccination included desire to wait and see if the vaccine is safe (56%); concerns over side effects (53%); and believing others are in greater need of the vaccine (44%).
With 24% of young adults hesitant to accept a COVID-19 vaccine, public health interventions should target reasons for hesitancy, address concerns about safety and side effects, and underscore the importance of vaccinations for this population.
The bone marrow microenvironment has a key role in regulating haematopoiesis, but its molecular complexity and response to stress are incompletely understood. Here we map the transcriptional ...landscape of mouse bone marrow vascular, perivascular and osteoblast cell populations at single-cell resolution, both at homeostasis and under conditions of stress-induced haematopoiesis. This analysis revealed previously unappreciated levels of cellular heterogeneity within the bone marrow niche and resolved cellular sources of pro-haematopoietic growth factors, chemokines and membrane-bound ligands. Our studies demonstrate a considerable transcriptional remodelling of niche elements under stress conditions, including an adipocytic skewing of perivascular cells. Among the stress-induced changes, we observed that vascular Notch delta-like ligands (encoded by Dll1 and Dll4) were downregulated. In the absence of vascular Dll4, haematopoietic stem cells prematurely induced a myeloid transcriptional program. These findings refine our understanding of the cellular architecture of the bone marrow niche, reveal a dynamic and heterogeneous molecular landscape that is highly sensitive to stress and illustrate the utility of single-cell transcriptomic data in evaluating the regulation of haematopoiesis by discrete niche populations.
Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear ...how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.
The increasing quantity of plastic waste in the ocean is providing a growing and more widespread novel habitat for microbes. Plastics have taxonomically distinct microbial communities (termed the ...‘Plastisphere’) and can raft these unique communities over great distances. In order to understand the Plastisphere properly it will be important to work out how major ocean changes (such as warming, acidification and deoxygenation) are shaping microbial communities on waste plastics in marine environments. Here, we show that common plastic drinking bottles rapidly become colonised by novel biofilm-forming bacterial communities, and that ocean acidification greatly influences the composition of plastic biofilm assemblages. We highlight the potential implications of this community shift in a coastal community exposed to enriched CO2 conditions.
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•Plastic will act as a novel ecological habitat for microbial communities.•Plastics harbour taxonomically distinct microbial communities (“Plastisphere”).•Ocean acidification greatly influences the Plastisphere community composition.
We report the development of an open-source experimental design via Bayesian optimization platform for multi-objective reaction optimization. Using high-throughput experimentation (HTE) and virtual ...screening data sets containing high-dimensional continuous and discrete variables, we optimized the performance of the platform by fine-tuning the algorithm components such as reaction encodings, surrogate model parameters, and initialization techniques. Having established the framework, we applied the optimizer to real-world test scenarios for the simultaneous optimization of the reaction yield and enantioselectivity in a Ni/photoredox-catalyzed enantioselective cross-electrophile coupling of styrene oxide with two different aryl iodide substrates. Starting with no previous experimental data, the Bayesian optimizer identified reaction conditions that surpassed the previously human-driven optimization campaigns within 15 and 24 experiments, for each substrate, among 1728 possible configurations available in each optimization. To make the platform more accessible to nonexperts, we developed a graphical user interface (GUI) that can be accessed online through a web-based application and incorporated features such as condition modification on the fly and data visualization. This web application does not require software installation, removing any programming barrier to use the platform, which enables chemists to integrate Bayesian optimization routines into their everyday laboratory practices.
Aging reduces skeletal muscle mass and strength, but the underlying molecular mechanisms remain elusive. Here, we used mouse models to investigate molecular mechanisms of age-related skeletal muscle ...weakness and atrophy as well as new potential interventions for these conditions. We identified two small molecules that significantly reduce age-related deficits in skeletal muscle strength, quality, and mass: ursolic acid (a pentacyclic triterpenoid found in apples) and tomatidine (a steroidal alkaloid derived from green tomatoes). Because small molecule inhibitors can sometimes provide mechanistic insight into disease processes, we used ursolic acid and tomatidine to investigate the pathogenesis of age-related muscle weakness and atrophy. We found that ursolic acid and tomatidine generate hundreds of small positive and negative changes in mRNA levels in aged skeletal muscle, and the mRNA expression signatures of the two compounds are remarkably similar. Interestingly, a subset of the mRNAs repressed by ursolic acid and tomatidine in aged muscle are positively regulated by activating transcription factor 4 (ATF4). Based on this finding, we investigated ATF4 as a potential mediator of age-related muscle weakness and atrophy. We found that a targeted reduction in skeletal muscle ATF4 expression reduces age-related deficits in skeletal muscle strength, quality, and mass, similar to ursolic acid and tomatidine. These results elucidate ATF4 as a critical mediator of age-related muscle weakness and atrophy. In addition, these results identify ursolic acid and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and atrophy in aged skeletal muscle.
Background: Aging reduces skeletal muscle strength and mass.
Results: The transcription factor ATF4 is required for age-related muscle weakness and atrophy, and the small molecules ursolic acid and tomatidine reduce ATF4 activity, weakness, and atrophy in aged skeletal muscle.
Conclusion: ATF4 is an essential mediator of muscle aging.
Significance: These results identify new strategies for reducing weakness and muscle loss during aging.
Immobilization causes skeletal muscle atrophy via complex signaling pathways that are not well understood. To better understand these pathways, we investigated the roles of p53 and ATF4, two ...transcription factors that mediate adaptations to a variety of cellular stresses. Using mouse models, we demonstrate that 3 days of muscle immobilization induces muscle atrophy and increases expression of p53 and ATF4. Furthermore, muscle fibers lacking p53 or ATF4 are partially resistant to immobilization-induced muscle atrophy, and forced expression of p53 or ATF4 induces muscle fiber atrophy in the absence of immobilization. Importantly, however, p53 and ATF4 do not require each other to promote atrophy, and coexpression of p53 and ATF4 induces more atrophy than either transcription factor alone. Moreover, muscle fibers lacking both p53 and ATF4 are more resistant to immobilization-induced atrophy than fibers lacking only p53 or ATF4. Interestingly, the independent and additive nature of the p53 and ATF4 pathways allows for combinatorial control of at least one downstream effector, p21. Using genome-wide mRNA expression arrays, we identified p21 mRNA as a skeletal muscle transcript that is highly induced in immobilized muscle via the combined actions of p53 and ATF4. Additionally, in mouse muscle, p21 induces atrophy in a manner that does not require immobilization, p53 or ATF4, and p21 is required for atrophy induced by immobilization, p53, and ATF4. Collectively, these results identify p53 and ATF4 as essential and complementary mediators of immobilization-induced muscle atrophy and discover p21 as a critical downstream effector of the p53 and ATF4 pathways.
Young adult anxiety/depression (mental health) symptoms have increased from prior to the COVID-19 pandemic. This study assessed young adult (aged 18–25 years) anxiety/depressive symptoms, mental ...health care utilization (prescription drug use, counseling, and/or either), and unmet counseling/therapy needs utilizing the national Household Pulse Survey data from June to July 2021.
Young adult (n = 2,809) rates and subgroup differences in mental health symptoms (Generalized Anxiety Disorder-2 and/or Patient Health Questionnaire-2) were assessed, as were mental health care utilization and unmet counseling/therapy needs.
In total, 48% of young adults had mental health symptoms. Among those, 39% received treatment and 36% reported unmet mental health counseling/therapy needs.
These findings highlight young adults' ongoing mental health needs and low services receipt. Interventions and further research to reduce barriers to seeking and utilizing mental health care and to increase the capacity of providers to deliver culturally appropriate mental health care are needed.
Abstract The femoral component and proprietary instrumentation of a mobile-bearing unicompartmental knee arthroplasty (UKA) was redesigned with an additional peg for enhanced fixation, 15° of extra ...femoral surface for contact in deep flexion, more rounded profile, better fit into the milled surface, and redesigned intramedullary based instrumentation. To assess the benefit of these changes, we compared postoperative radiographs of 219 single-peg and 186 twin-peg UKAs done in 2008–2011. All surviving knees demonstrated satisfactory position and alignment with no radiolucencies observed. Radiographic analysis showed improved and consistent component positioning with the twin-peg design implanted with updated instrumentation compared with the single-peg. The radiographic benefits of improved implant positioning using the twin-peg component and updated instrumentation are clear and carry tremendous potential. More robust follow-up is imperative.
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