Observation of a promethium complex in solution.

Lanthanide rare-earth metals are ubiquitous in modern technologies1-5, but we know little about chemistry of the 61st element, promethium (Pm)6, a lanthanide that is highly radioactive and inaccessible. Despite its importance7,8, Pm has been conspicuously absent from the experimental studies of lanthanides, impeding our full comprehension of the so-called lanthanide contraction phenomenon: a fundamental aspect of the periodic table that is quoted in general chemistry textbooks. Here we demonstrate a stable chelation of the 147Pm radionuclide (half-life of 2.62 years) in aqueous solution by the newly synthesized organic diglycolamide ligand. The resulting homoleptic PmIII complex is studied using synchrotron X-ray absorption spectroscopy and quantum chemical calculations to establish the coordination structure and a bond distance of promethium. These fundamental insights allow a complete structural investigation of a full set of isostructural lanthanide complexes, ultimately capturing the lanthanide contraction in solution solely on the basis of experimental observations. Our results show accelerated shortening of bonds at the beginning of the lanthanide series, which can be correlated to the separation trends shown by diglycolamides9-11. The characterization of the radioactive PmIII complex in an aqueous environment deepens our understanding of intra-lanthanide behaviour12-15 and the chemistry and separation of the f-block elements16.

A concept for international societally relevant microbiology education and microbiology knowledge promulgation in society.

EXECUTIVE SUMMARY: Microbes are all pervasive in their distribution and influence on the functioning and well-being of humans, life in general and the planet. Microbially-based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision-makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative-the IMiLI-is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence-based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner-centric, not academic microbiology-centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators-learners. As such, they will collect and analyse feedback from the end-users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators-learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships-a global societally relevant microbiology education ecosystem-in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient. ABSTRACT: The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well-being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us-individuals/communities/nations/the human world-and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. HERE, WE PRESENT: our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision-making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner-centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091-1111). Importantly, although the primary target of the freely available (CC BY-NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity-driven, web-based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.

Long-term consequences of mothers' and fathers' wartime deployments: Protocol for a two-wave panel study.

Multiple adjustment difficulties have been associated with children's exposure to recent parental wartime military deployments, but long-term consequences have not yet been systematically studied. This investigation will assess direct and indirect relationships between exposures to parental deployments early in life and later youth adjustment. Parents' psychological health and family processes will be examined as mediators, and parents' and children's vulnerability and support will be examined as moderators. Archival data will be combined with new data gathered from two children and up to two parents in families where children will be aged 11 to 16 at the first data collection and will have experienced at least one parental deployment, for at least one child prior to age 6. Data are being gathered via telephone interviews and web-based surveys conducted twice one year apart. Outcomes are indicators of children's social-emotional development, behavior, and academic performance. Notable features of this study include oversampling of female service members, inclusion of siblings, and inclusion of families of both veterans and currently serving members. This study has potentially important implications for schools, community organizations and health care providers serving current and future cohorts of military and veteran families.

Feasibility and acceptability of chaplain decision coaching on Periviable resuscitation decision quality: A pilot study.

Objective: To pilot test and assess the feasibility and acceptability of chaplain-led decision coaching alongside the GOALS (Getting Optimal Alignment around Life Support) decision support tool to enhance decision-making in threatened periviable delivery. Methods: Pregnant people admitted for threatened periviable delivery and their 'important other' (IO) were enrolled. Decisional conflict, acceptability, and knowledge were measured before and after the intervention. Chaplains journaled their impressions of training and coaching encounters. Descriptive analysis and conventional content analysis were completed. Results: Eight pregnant people and two IOs participated. Decisional conflict decreased by a mean of 6.7 (SD = 9.4) and knowledge increased by a mean of 1.4 (SD = 1.8). All rated their experience as "good" or "excellent," and the amount of information was "just right." Participants found it "helpful to have someone to talk to" and noted chaplains helped them reach a decision. Chaplains found the intervention a valuable use of their time and skillset. Conclusion: This is the first small-scale pilot study to utilize chaplains as decision coaches. Our results suggest that chaplain coaching with a decision support tool is feasible and well-accepted by parents and chaplains. Innovations: Our findings recognize chaplains as an underutilized, yet practical resource in value-laden clinical decision-making.

Plant seedlings of peas, tomatoes, and cucumbers exude compounds that are needed for growth and chemoattraction of Rhizobium leguminosarum bv. viciae 3841 and Azospirillum brasilense Sp7.

This study characterizes seedling exudates of peas, tomatoes, and cucumbers at the level of chemical composition and functionality. A plant experiment confirmed that Rhizobium leguminosarum bv. viciae 3841 enhanced growth of pea shoots, while Azospirillum brasilense Sp7 supported growth of pea, tomato, and cucumber roots. Chemical analysis of exudates after 1 day of seedling incubation in water yielded differences between the exudates of the three plants. Most remarkably, cucumber seedling exudate did not contain detectable sugars. All exudates contained amino acids, nucleobases/nucleosides, and organic acids, among other compounds. Cucumber seedling exudate contained reduced glutathione. Migration on semi solid agar plates containing individual exudate compounds as putative chemoattractants revealed that R. leguminosarum bv. viciae was more selective than A. brasilense, which migrated towards any of the compounds tested. Migration on semi solid agar plates containing 1:1 dilutions of seedling exudate was observed for each of the combinations of bacteria and exudates tested. Likewise, R. leguminosarum bv. viciae and A. brasilense grew on each of the three seedling exudates, though at varying growth rates. We conclude that the seedling exudates of peas, tomatoes, and cucumbers contain everything that is needed for their symbiotic bacteria to migrate and grow on.

Novice Preceptors Facilitating Nursing Student Clinicals: A Roadmap for Success.

Nursing professional development practitioners rely on nurse preceptors to guide the development of nursing staff and students. A lack of experienced preceptors may require individuals who have limited to no experience in precepting to serve in the preceptor role. Nursing professional development practitioners should be prepared to effectively support and develop novice preceptors. This article analyzes the development and implementation of a novel educational resource that assists the novice preceptor in facilitating nursing student clinicals.

Universal Digital High-Resolution Melt Analysis for the Diagnosis of Bacteremia.

Fast and accurate diagnosis of bloodstream infection is necessary to inform treatment decisions for septic patients, who face hourly increases in mortality risk. Blood culture remains the gold standard test but typically requires approximately 15 hours to detect the presence of a pathogen. We, therefore, assessed the potential for universal digital high-resolution melt (U-dHRM) analysis to accomplish faster broad-based bacterial detection, load quantification, and species-level identification directly from whole blood. Analytical validation studies demonstrated strong agreement between U-dHRM load measurement and quantitative blood culture, indicating that U-dHRM detection is highly specific to intact organisms. In a pilot clinical study of 17 whole blood samples from pediatric patients undergoing simultaneous blood culture testing, U-dHRM achieved 100% concordance when compared with blood culture and 88% concordance when compared with clinical adjudication. Moreover, U-dHRM identified the causative pathogen to the species level in all cases where the organism was represented in the melt curve database. These results were achieved with a 1-mL sample input and sample-to-answer time of 6 hours. Overall, this pilot study suggests that U-dHRM may be a promising method to address the challenges of quickly and accurately diagnosing a bloodstream infection.

Multisite Implementation of the Tiered Skills Acquisition Model for Orientation: Review and Analysis.

Nursing professional development (NPD) directors and practitioners are called to lead practice changes. Knowledge of implementation science and diffusion theory equips NPD professionals with the tools necessary for successfully influencing nursing practice. This article analyzes a multisite implementation of the tiered skills acquisition model for clinical orientation and provides NPD directors and practitioners with recommendations for effective implementation strategies that translate beyond clinical orientation to a variety of NPD programs and initiatives. [J Contin Educ Nurs. 2024;55(3):130-136.].

Mesoaccumbal glutamate neurons drive reward via glutamate release but aversion via dopamine co-release.

Ventral tegmental area (VTA) projections to the nucleus accumbens (NAc) drive reward-related motivation. Although dopamine neurons are predominant, a substantial glutamatergic projection is also present, and a subset of these co-release both dopamine and glutamate. Optogenetic stimulation of VTA glutamate neurons not only supports self-stimulation but can also induce avoidance behavior, even in the same assay. Here, we parsed the selective contribution of glutamate or dopamine co-release from VTA glutamate neurons to reinforcement and avoidance. We expressed channelrhodopsin-2 (ChR2) in mouse VTA glutamate neurons in combination with CRISPR-Cas9 to disrupt either the gene encoding vesicular glutamate transporter 2 (VGLUT2) or tyrosine hydroxylase (Th). Selective disruption of VGLUT2 abolished optogenetic self-stimulation but left real-time place avoidance intact, whereas CRISPR-Cas9 deletion of Th preserved self-stimulation but abolished place avoidance. Our results demonstrate that glutamate release from VTA glutamate neurons is positively reinforcing but that dopamine release from VTA glutamate neurons can induce avoidance behavior.

(p)ppGpp is required for virulence of Shigella flexneri.

Infection by the enteric pathogen Shigella flexneri requires transit through the gastrointestinal tract and invasion of and replication within the cells of the host colonic epithelium. This process exposes the pathogen to a range of diverse microenvironments. Furthermore, the unique composition and physical environment of the eukaryotic cell cytosol represents a stressful environment for S. flexneri, and extensive physiological adaptations are needed for the bacterium to thrive. In this work, we show that disrupting synthesis of the stringent response alarmone (p)ppGpp in S. flexneri diminished expression of key virulence genes, including ipaA, ipaB, ipaC, and icsA, and it reduced bacterial invasion and intercellular spread. Deletion of the (p)ppGpp synthase gene relA alone had no effect on S. flexneri virulence, but disruption of both relA and the (p)ppGpp synthase/hydrolase gene spoT resulted in loss of (p)ppGpp synthesis and virulence. While the relA spoT deletion mutant was able to invade a cultured human epithelial cell monolayer, albeit at reduced levels, it was unable to maintain the infection and spread to adjacent cells, as indicated by loss of plaque formation. Complementation with spoT on a plasmid vector restored plaque formation. Thus, SpoT alone is sufficient to provide the necessary level of (p)ppGpp for virulence. These results indicate that (p)ppGpp is required for S. flexneri virulence and adaptation to the intracellular environment, adding to the repertoire of signaling pathways that affect Shigella pathogenesis.

Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection.

Cytomegalovirus is the most common cause of congenital infectious disease and the leading nongenetic etiology of sensorineural hearing loss. Although most infected neonates are asymptomatic at birth, congenital cytomegalovirus infection is responsible for nearly 400 infant deaths annually in the United States and may lead to significant long-term neurodevelopmental impairments in survivors. The resulting financial and social burdens of congenital cytomegalovirus infection have led many medical centers to initiate targeted testing after birth, with a growing advocacy to advance universal newborn screening. While no cures or vaccines are currently available to eliminate or prevent cytomegalovirus infection, much has been learned over the last five years regarding disease pathophysiology and viral replication cycles that may enable the development of innovative diagnostics and therapeutics. This Review will detail our current understanding of congenital cytomegalovirus infection, while focusing our discussion on routine and emerging diagnostics for viral detection, quantification, and long-term prognostication. IMPACT: This review highlights our current understanding of the fetal transmission of human cytomegalovirus. It details clinical signs and physical findings of congenital cytomegalovirus infection. This submission discusses currently available cytomegalovirus diagnostics and introduces emerging platforms that promise improved sensitivity, specificity, limit of detection, viral quantification, detection of genomic antiviral resistance, and infection staging (primary, latency, reactivation, reinfection).

Composite environmental indices-a case of rickety rankings.

Composite indices have been widely used to rank the environmental performance of nations. Such environmental indices can be useful in communicating complex information as a single value and have the potential to generate political and media awareness of environmental issues. However, poorly constructed, or poorly communicated indices, can hinder efforts to identify environmental failings, and there are considerable differences in rank among existing environmental indices. Here, we provide a review of the conceptual frameworks and methodological choices used for existing environmental indices to enhance our understanding of their accuracy and applicability. In the present study, we review existing global indices according to their conceptual framework (objectives of the index and set of indicators included) and methodological choices made in their construction (e.g., weighting and aggregation). We examine how differences in conceptual frameworks and methodology may yield a more, or less, optimistic view of a country's environment. Our results indicate that (1) multidimensional environmental indices with indicators related to human health and welfare or policy are positively correlated; (2) environment-only indices are positively correlated with one another or are not correlated at all; (3) multidimensional indices and environment-only indices are negatively correlated with each other or are not correlated at all. This indicates that the conceptual frameworks and indicators included may influence a country's rank among different environmental indices. Our results highlight that, when choosing an existing environmental index-or developing a new one-it is important to assess whether the conceptual framework (and associated indicators) and methodological choices are appropriate for the phenomenon being measured and reported on. This is important because the inclusion of confounding indicators in environmental indices may provide a misleading view of the quality of a country's environment.

A broad-based probe-free qPCR assay for detection and discrimination of three human herpes viruses.

Primary infection or reactivation of latent human cytomegalovirus (HCMV) or herpes simplex viruses (HSV) 1 or 2 during pregnancy can transmit the virus in utero or during natural childbirth to the fetus. The majority of these infections are asymptomatic at birth but may present later with potentially lethal disseminated infection or meningitis (HSV), or long-term neurodevelopmental sequelae including sensorineural hearing loss or neurodevelopmental impairments (HCMV). Unfortunately, early signs and symptoms of disseminated viral infections may be misdiagnosed as bacterial sepsis. Therefore, immediate testing for viral etiologies may not be ordered or even considered by skilled clinicians. In asymptomatic HCMV infections, early detection is necessary to monitor for and treat future neurologic sequelae. In acutely ill-appearing infants, specific detection of viruses against other disease-causing agents is vital to inform correct patient management, including early administration of the correct antimicrobial(s). An ideal test should be rapid, inexpensive, require low sample volumes, and demonstrate efficacy in multiple tissue matrices to aid in timely clinical decision-making for neonatal infections. This work discusses the development of a rapid probe-free qPCR assay for HSV and HCMV that enables early and specific detection of these viruses in neonates. The assay's probe free chemistry would allow easier extension to a broad-based multiplexed pathogenic panel as compared to assays utilizing sequence-specific probes or nested PCR.

Universal digital high resolution melt analysis for the diagnosis of bacteremia.

Fast and accurate diagnosis of bloodstream infection is necessary to inform treatment decisions for septic patients, who face hourly increases in mortality risk. Blood culture remains the gold standard test but typically requires ∼15 hours to detect the presence of a pathogen. Here, we assess the potential for universal digital high-resolution melt (U-dHRM) analysis to accomplish faster broad-based bacterial detection, load quantification, and species-level identification directly from whole blood. Analytical validation studies demonstrated strong agreement between U-dHRM load measurement and quantitative blood culture, indicating that U-dHRM detection is highly specific to intact organisms. In a pilot clinical study of 21 whole blood samples from pediatric patients undergoing simultaneous blood culture testing, U-dHRM achieved 100% concordance when compared with blood culture and 90.5% concordance when compared with clinical adjudication. Moreover, U-dHRM identified the causative pathogen to the species level in all cases where the organism was represented in the melt curve database. These results were achieved with a 1 mL sample input and sample-to-answer time of 6 hrs. Overall, this pilot study suggests that U-dHRM may be a promising method to address the challenges of quickly and accurately diagnosing a bloodstream infection. Universal digital high resolution melt analysis for the diagnosis of bacteremia: April Aralar, Tyler Goshia, Nanda Ramchandar, Shelley M. Lawrence, Aparajita Karmakar, Ankit Sharma, Mridu Sinha, David Pride, Peiting Kuo, Khrissa Lecrone, Megan Chiu, Karen Mestan, Eniko Sajti, Michelle Vanderpool, Sarah Lazar, Melanie Crabtree, Yordanos Tesfai, Stephanie I. Fraley.

Divide and conquer: genetics, mechanism, and evolution of the ferrous iron transporter Feo in Helicobacter pylori.

Introduction: Feo is the most widespread and conserved system for ferrous iron uptake in bacteria, and it is important for virulence in several gastrointestinal pathogens. However, its mechanism remains poorly understood. Hitherto, most studies regarding the Feo system were focused on Gammaproteobacterial models, which possess three feo genes (feoA, B, and C) clustered in an operon. We found that the human pathogen Helicobacter pylori possesses a unique arrangement of the feo genes, in which only feoA and feoB are present and encoded in distant loci. In this study, we examined the functional significance of this arrangement. Methods: Requirement and regulation of the individual H. pylori feo genes were assessed through in vivo assays and gene expression profiling. The evolutionary history of feo was inferred via phylogenetic reconstruction, and AlphaFold was used for predicting the FeoA-FeoB interaction. Results and Discussion: Both feoA and feoB are required for Feo function, and feoB is likely subjected to tight regulation in response to iron and nickel by Fur and NikR, respectively. Also, we established that feoA is encoded in an operon that emerged in the common ancestor of most, but not all, helicobacters, and this resulted in feoA transcription being controlled by two independent promoters. The H. pylori Feo system offers a new model to understand ferrous iron transport in bacterial pathogens.

Red Blood Cell Conservation and Use in the Cardiovascular Operating Rooms at Ben Taub General Hospital.

OBJECTIVES: A conservative hemoglobin transfusion threshold is noninferior to a liberal threshold in cardiac surgery. However, red blood cell (RBC) transfusion remains common during cardiac surgery. The authors' single-center, retrospective study aimed to decrease RBC transfusions for hemoglobin >7.5 g/dL in nonemergent cardiovascular surgeries utilizing cardiopulmonary bypass (CPB), by educating the anesthesiology and surgical staff on the benefits of a conservative threshold for transfusions, and incorporating the discussion and routine use of blood conservation methods for all nonemergent cardiac surgeries. DESIGN: This was a single-center, retrospective study that included all nonemergent coronary artery bypass grafting and single-valve cases utilizing CPB from January 2018 to December 2021 before and after the intervention in July 2019. SETTING: The data involved a single community hospital. PARTICIPANTS: A total of 417 patients were included in the study. INTERVENTIONS: The authors adopted a conservative threshold for blood transfusion and implemented a collaborative multidisciplinary approach to blood conservation. MEASUREMENTS AND MAIN RESULTS: Baseline patient characteristics were summarized, and the incidence of RBC transfusion before and after the intervention on July 26, 2019, were compared by Wilcoxon rank sum and chi-square tests. Multivariate logistic regression was used. The intervention was significantly associated with reduced RBC transfusion rate after adjusting for confounding variables (p < 0.05). The odds of receiving an RBC transfusion among patients after the intervention was 0.615 times the odds among patients before intervention (95% CI: 0.3913-0.9663). CONCLUSIONS: The authors' goal was to improve patient outcomes and the quality of perioperative care during cardiac surgery. By implementing a protocol and educating anesthesiologists, surgeons, and perfusionists, they successfully decreased the incidence of RBC transfusion above a hemoglobin of 7.5 g/dL.

Relationship Maintenance among Military Couples.

A burgeoning body of research on the relationship maintenance of military couples over the past two decades suggests the time is right to organize, assimilate, and critique the literature. We conducted a systematic review informed by the integrative model of relationship maintenance (Ogolsky et al., 2017) that considered issues of intersectionality (Crenshaw, 1991). Our literature search identified 81 relevant journal articles representing 62 unique samples. With respect to theory, 59.3% of the journal articles employed one or more formal theoretical frameworks. In terms of research design, 88.7% of the studies focused on the U.S. military, 83.9% of the studies recruited convenience samples, 54.8% of the studies utilized quantitative methods, and 30.6% of the studies collected longitudinal data. Among the studies reporting sample demographics, 96.8% of participants were married, 77.2% of participants identified as non-Hispanic White, and only one same-sex relationship was represented. Our narrative synthesis integrated findings about relationship maintenance from studies examining (a) relationship maintenance overtly, (b) communicating to stay connected across the deployment cycle, (c) disclosure and protective buffering, (d) support from a partner, (e) dyadic coping, and (f) caregiving and accommodating a partner's symptoms. We interpret our results with an eye toward advancing theory, research, and practice.

Immune checkpoint therapy-current perspectives and future directions.

Immune checkpoint therapy (ICT) has dramatically altered clinical outcomes for cancer patients and conferred durable clinical benefits, including cure in a subset of patients. Varying response rates across tumor types and the need for predictive biomarkers to optimize patient selection to maximize efficacy and minimize toxicities prompted efforts to unravel immune and non-immune factors regulating the responses to ICT. This review highlights the biology of anti-tumor immunity underlying response and resistance to ICT, discusses efforts to address the current challenges with ICT, and outlines strategies to guide the development of subsequent clinical trials and combinatorial efforts with ICT.

Vibrio cholerae Alkalizes Its Environment via Citrate Metabolism to Inhibit Enteric Growth In Vitro.

Vibrio cholerae is a Gram-negative pathogen, living in constant competition with other bacteria in marine environments and during human infection. One competitive advantage of V. cholerae is the ability to metabolize diverse carbon sources, such as chitin and citrate. We observed that when some V. cholerae strains were grown on a medium with citrate, the medium's chemical composition turned into a hostile alkaline environment for Gram-negative bacteria, such as Escherichia coli and Shigella flexneri. We found that although the ability to exclude competing bacteria was not contingent on exogenous citrate, V. cholerae C6706 citrate metabolism mutants ΔoadA-1, ΔcitE, and ΔcitF were not able to inhibit S. flexneri or E. coli growth. Lastly, we demonstrated that while the V. cholerae C6706-mediated increased medium pH was necessary for the enteric exclusion phenotype, secondary metabolites, such as bicarbonate (protonated to carbonate in the raised pH) from the metabolism of citrate, enhanced the ability to inhibit the growth of E. coli. These data provide a novel example of how V. cholerae outcompetes other Gram-negative bacteria. IMPORTANCE Vibrio cholerae must compete with other bacteria in order to cause disease. Here, we show that V. cholerae creates an alkaline environment, which is able to inhibit the growth of other enteric bacteria. We demonstrate that V. cholerae environmental alkalization is linked to the capacity of the bacteria to metabolize citrate. This behavior could potentially contribute to V. cholerae's ability to colonize the human intestine.