Explore the vast range of titles available.

There is a 17-year gap between the publication of research which proves an intervention is  efficacious and effective and the implementation of that same intervention into practice [1]. In behavioral health, only 14% of successful interventions are integrated into actual practice [2]. As such, Implementation Science is envisioned to address the research to practice gap. This research methodology becomes important as it looks to investigate how to get interventions to become embedded in practice and de-implement unproven or disproven interventions that may be harmful and/or ineffective for patients. The aim of this commentary is to raise awareness of health sciences librarians/information specialists about this research arena and encourage health sciences librarians to envision how they could be involved in implementation science projects and teams or even use implementation science in their practice.

Objective Chronic diseases are the leading causes of death and disability in the U.S., and disease management largely falls onto patients’ family caregivers. The long-term burden and stress of caregiving negatively impact caregivers’ well-being and ability to provide care. Digital health interventions have the potential to support caregivers. This article aims to provide an updated review of interventions using digital health tools to support family caregivers and the scope of the Human-Centered Design (HCD) approaches. Methods We conducted a systematic search on July 2019 and January 2021 in PubMed, CINAHL, Embase, Cochrane Library, PsycINFO, ERIC, and ACM Digital Library, limiting to 2014–2021 to identify family caregiver interventions assisted by modern technologies. The Mixed Methods Appraisal Tool and the Grading of Recommendations Assessment, Development and Evaluation were used to evaluate the articles. Data were abstracted and evaluated using Rayyan and Research Electronic Data Capture. Results We identified and reviewed 40 studies from 34 journals, 10 fields, and 19 countries. Findings included patients’ conditions and relationships with family caregivers, how the technology is used to deliver the intervention, HCD methods, theoretical frameworks, components of the interventions, and family caregiver health outcomes. Conclusion This updated and expanded review revealed that digitally enhanced health interventions were robust at providing high-quality assistance and support to caregivers by improving caregiver psychological health, self-efficacy, caregiving skills, quality of life, social support, and problem-coping abilities. Health professionals need to include informal caregivers as an essential component when providing care to patients. Future research should include more marginalized caregivers from diverse backgrounds, improve the accessibility and usability of the technology tools, and tailor the intervention to be more culturally and linguistically sensitive.

We report a previously undescribed quorum-sensing mechanism for triggering multicellularity in Bacillus subtilis. B. subtilis forms communities of cells known as biofilms in response to an unknown signal. We discovered that biofilm formation is stimulated by a variety of small molecules produced by bacteria--including the B. subtilis nonribosomal peptide surfactin--that share the ability to induce potassium leakage. Natural products that do not cause potassium leakage failed to induce multicellularity. Small-molecule-induced multicellularity was prevented by the addition of potassium, but not sodium or lithium. Evidence is presented that potassium leakage stimulates the activity of a membrane protein kinase, KinC, which governs the expression of genes involved in biofilm formation. We propose that KinC responds to lowered intracellular potassium concentration and that this is a quorum-sensing mechanism that enables B. subtilis to respond to related and unrelated bacteria.

Mycobacterium tuberculosis and its close relative Mycobacterium marinum infect macrophages and induce the formation of granulomas, organized macrophage-rich immune aggregates. These mycobacterial pathogens can accelerate and co-opt granuloma formation for their benefit, using the specialized secretion system ESX-1, a key virulence determinant. ESX-1–mediated virulence is attributed to the damage it causes to the membranes of macrophage phagosomal compartments, within which the bacteria reside. This phagosomal damage, in turn, has been attributed to the membranolytic activity of ESAT-6, the major secreted substrate of ESX-1. However, mutations that perturb ESAT-6’s membranolytic activity often result in global impairment of ESX-1 secretion. This has precluded an understanding of the causal and mechanistic relationships between ESAT-6 membranolysis and ESX-1–mediated virulence. Here, we identify two conserved residues in the unstructured C-terminal tail of ESAT-6 required for phagosomal damage, granuloma formation, and virulence. Importantly, these ESAT-6 mutants have near-normal levels of secretion, far higher than the minimal threshold we establish is needed for ESX-1–mediated virulence early in infection. Unexpectedly, these loss-of-function ESAT-6 mutants retain the ability to lyse acidified liposomes. Thus, ESAT-6’s virulence functions in vivo can be uncoupled from this in vitro surrogate assay. These uncoupling mutants highlight an enigmatic functional domain of ESAT-6 and provide key tools to investigate the mechanism of phagosomal damage and virulence.

Web-based interventions aimed at supporting informal caregivers of people living with dementia have the potential to improve caregivers' well-being and psychological health. However, few interventions are widely implemented for this population, and none of the prior reviews have systematically examined the use of behavior change techniques (BCTs), theories, and agents in web-based interventions for informal caregivers of people living with dementia. To better understand this implementation gap, we reviewed the literature to map behavioral factors (BCTs, theories, and agents) deployed in the studies. Furthermore, because there is an emerging consensus that retention could be shaped by participant characteristics and behavioral factors, we explored relationships between these features and retention rates across studies. We pursued 3 objectives: to map behavioral factors involved in the web-based interventions for informal caregivers of people living with dementia; to examine the relationship between behavioral change elements and retention in the studies; and to examine the relationship between participant characteristics (gender, age, and spouse or adult children caregiver proportion) and study retention. We conducted a literature review using the following keywords and their corresponding Medical Subject Headings terms: dementia, caregivers, and web-based intervention. The time limits were January 1998 to March 2022. Using the BCTv1 taxonomy, which specifies active behavioral components in interventions, 2 coders collected, summarized, and analyzed the frequency distributions of BCTs. Similarly, they abstracted and analyzed participant characteristics, behavior change theories, behavior change agents, and retention rates in the studies. The average age was 61.5 (SD 7.4) years, and the average proportion of spousal informal caregivers, adult children informal caregivers, and retention rates were 51.2% (SD 24.8%), 44.8% (SD 22%), and 70.4% (SD 17%), respectively. Only 53% (17/32) of the studies used behavior change theories, but 81% (26/32) included behavior change agents. The most common BCTv1 clusters were shaping knowledge and social support. The median number of BCTv1 clusters was 5 (IQR 3). We observed a negative correlation between the proportion of spousal informal caregivers and the retention rate (r=-0.45; P=.02) and between the number of BCTv1 clusters and retention rates (r=-0.47; P=.01). We also found that the proportion of adult children informal caregivers in the study was significantly and positively correlated with the retention rate (r=0.5; P=.03). No other participant characteristics or behavioral factors were associated with retention rates. We found that almost half of the studies were not informed by behavior change theories. In addition, spousal involvement and a higher number of BCTs were each associated with lower retention rates, while the involvement of adult children caregivers in the study was associated with higher retention. In planning future studies, researchers should consider matching participant characteristics with their intended intervention as the alignment might improve their retention rates.

To assess the role and effectiveness of the mnemonic PICO (Population, Intervention, Comparator and Outcome) in evidence-based practice (EBP) pedagogy. The mnemonic “PICO” is a well-established tool in nursing EBP pedagogy. Nevertheless, application of this tool in nursing curricula is not currently supported by evidence of its effectiveness. Further, there are reports that PICO as a tool is unhelpful in the classroom. We reviewed the literature on PICO; specifically, the mnemonic’s origin, purpose, and effectiveness in practice. Our analysis reveals that PICO is limited in terms of its effectiveness and scope of inquiry. A reevaluation of PICO's role in nursing pedagogy is essential. To start, we propose a de-emphasis on PICO as an exclusive or preferred tool, and an emphasis on critical evaluation of the literature, and the whole of the EBP process. We propose a search for more effective methods to improve matching native clinical questions to the retrieval of data that informs patient care.

Background Methane-utilizing bacteria (methanotrophs) are capable of growth on methane and are attractive systems for bio-catalysis. However, the application of natural methanotrophic strains to large-scale production of value-added chemicals/biofuels requires a number of physiological and genetic alterations. An accurate metabolic model coupled with flux balance analysis can provide a solid interpretative framework for experimental data analyses and integration. Results A stoichiometric flux balance model of Methylomicrobium buryatense strain 5G(B1) was constructed and used for evaluating metabolic engineering strategies for biofuels and chemical production with a methanotrophic bacterium as the catalytic platform. The initial metabolic reconstruction was based on whole-genome predictions. Each metabolic step was manually verified, gapfilled, and modified in accordance with genome-wide expression data. The final model incorporates a total of 841 reactions (in 167 metabolic pathways). Of these, up to 400 reactions were recruited to produce 118 intracellular metabolites. The flux balance simulations suggest that only the transfer of electrons from methanol oxidation to methane oxidation steps can support measured growth and methane/oxygen consumption parameters, while the scenario employing NADH as a possible source of electrons for particulate methane monooxygenase cannot. Direct coupling between methane oxidation and methanol oxidation accounts for most of the membrane-associated methane monooxygenase activity. However the best fit to experimental results is achieved only after assuming that the efficiency of direct coupling depends on growth conditions and additional NADH input (about 0.1–0.2 mol of incremental NADH per one mol of methane oxidized). The additional input is proposed to cover loss of electrons through inefficiency and to sustain methane oxidation at perturbations or support uphill electron transfer. Finally, the model was used for testing the carbon conversion efficiency of different pathways for C 1 -utilization, including different variants of the ribulose monophosphate pathway and the serine cycle. Conclusion We demonstrate that the metabolic model can provide an effective tool for predicting metabolic parameters for different nutrients and genetic perturbations, and as such, should be valuable for metabolic engineering of the central metabolism of M. buryatense strains.

Background Methane is a feedstock of interest for the future, both from natural gas and from renewable biogas sources. Methanotrophic bacteria have the potential to enable commercial methane bioconversion to value-added products such as fuels and chemicals. A strain of interest for such applications is Methylomicrobium buryatense 5GB1, due to its robust growth characteristics. However, to take advantage of the potential of this methanotroph, it is important to generate comprehensive bioreactor-based datasets for different growth conditions to compare bioprocess parameters. Results Datasets of growth parameters, gas utilization rates, and products (total biomass, extracted fatty acids, glycogen, excreted acids) were obtained for cultures of M. buryatense 5GB1 grown in continuous culture under methane limitation and O 2 limitation conditions. Additionally, experiments were performed involving unrestricted batch growth conditions with both methane and methanol as substrate. All four growth conditions show significant differences. The most notable changes are the high glycogen content and high formate excretion for cells grown on methanol (batch), and high O 2 :CH 4 utilization ratio for cells grown under methane limitation. Conclusions The results presented here represent the most comprehensive published bioreactor datasets for a gamma-proteobacterial methanotroph. This information shows that metabolism by M. buryatense 5GB1 differs significantly for each of the four conditions tested. O 2 limitation resulted in the lowest relative O 2 demand and fed-batch growth on methane the highest. Future studies are needed to understand the metabolic basis of these differences. However, these results suggest that both batch and continuous culture conditions have specific advantages, depending on the product of interest.

The bacteria that grow on methane aerobically (methanotrophs) support populations of non-methanotrophs in the natural environment by excreting methane-derived carbon. One group of excreted compounds are short-chain organic acids, generated in highest abundance when cultures are grown under O 2 -starvation. We examined this O 2 -starvation condition in the methanotroph Methylomicrobium buryatense 5GB1. The M. buryatense 5GB1 genome contains homologs for all enzymes necessary for a fermentative metabolism, and we hypothesize that a metabolic switch to fermentation can be induced by low-O 2 conditions. Under prolonged O 2 -starvation in a closed vial, this methanotroph increases the amount of acetate excreted about 10-fold, but the formate, lactate, and succinate excreted do not respond to this culture condition. In bioreactor cultures, the amount of each excreted product is similar across a range of growth rates and limiting substrates, including O 2 -limitation. A set of mutants were generated in genes predicted to be involved in generating or regulating excretion of these compounds and tested for growth defects, and changes in excretion products. The phenotypes and associated metabolic flux modeling suggested that in M. buryatense 5GB1, formate and acetate are excreted in response to redox imbalance. Our results indicate that even under O 2 -starvation conditions, M. buryatense 5GB1 maintains a metabolic state representing a combination of fermentation and respiration metabolism.

Many methylotrophs, microorganisms that consume carbon compounds lacking carbon–carbon bonds, use two different systems to oxidize methanol for energy production and biomass accumulation. The MxaFI methanol dehydrogenase (MDH) contains calcium in its active site, while the XoxF enzyme contains a lanthanide in its active site. The genes encoding the MDH enzymes are differentially regulated by the presence of lanthanides. In this study, we found that the histidine kinase MxaY controls the lanthanide-mediated switch in Methylomicrobium buryatense 5GB1C. MxaY controls the transcription of genes encoding MxaFI and XoxF at least partially by controlling the transcript levels of the orphan response regulator MxaB. We identify a constitutively active version of MxaY, and identify the mutated residue that may be involved in lanthanide sensing. Lastly, we find evidence to suggest that tight control of active MDH production is required for wild-type growth rates.