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Family researchers and policy makers are giving increasing attention to the consequences of immigration for families. Immigration affects the lives of family members who migrate as well as those who remain behind and has important consequences for family formation, kinship ties, living arrangements, and children's outcomes. We present a selective review of the literature on immigrant families in the United States, focusing on key research themes and needs. A summary of secondary data sets that can be used to study immigrant families is presented as well as suggestions for future research in this increasingly important area of family research and policy. [ABSTRACT FROM AUTHOR]

Background: Despite the effectiveness of breast cancer screening for women older than 50 years of age, only about one third of these women in the United States receive annual mammography.Purpose: This study was designed to determine if a community-wide intervention could increase use of mammography screening for breast cancer. Secondary end points were determination of changes in women's knowledge and attitudes toward mammography and physicians' self-reported screening practices.Methods: We conducted a controlled study from January 1987 through January 1990 in two eastern North Carolina communities--New Hanover County (the experimental community) and Pitt County (the control community). Before development and implementation of the intervention program in New Hanover County and after the program had been in operation for 1 year, 500 women of ages 50-74 years and all primary-care physicians in each community were interviewed by telephone. In these interviews, we determined the use of mammography for breast cancer screening and the knowledge and attitudes about it. We also established the number of screening mammograms performed in 1987 and 1989 in each county and reviewed medical records to determine the percentage of women the physicians had referred for mammograms.Results: The percentage of women who reported receiving a mammogram in the previous year increased from 35% to 55% in the experimental community and from 30% to 40% in the control community (difference of differences, 10%; P = .03 after adjustment for race, education, age, and having a regular doctor; 95% confidence interval, 1%-18%). Increases were greater in New Hanover County regardless of age, race, income, and education. However, the increase was less for Black women than for White women, both overall and in most demographic subgroups. The total number of mammograms performed increased 89% in the experimental community and 45% in the control community. Women's knowledge about mammography changed little, but the intention to get a mammogram increased 30% in New Hanover County, compared with a 17% increase in Pitt County--a statistically significant difference (P < .01). Physician reports and medical record reviews in the two communities showed similar increases in the number of mammograms ordered.Conclusions: A community-wide effort to increase use of breast cancer screening was successful, but more work must be done to reach the National Cancer Institute's goal of annual mammograms for 80% of women of ages 50-74. [ABSTRACT FROM AUTHOR]

Objective: To qualitatively understand and characterize the experience of racism in outpatient pediatric healthcare settings from the perspectives of Black families., Methods: We conducted focus groups with parents or guardians of Black children, recruited from academic primary care offices at a single pediatric institution. Focus groups were facilitated virtually by Black team members using an open-ended, semi-structured focus group guide. We analyzed focus group transcripts using iterative, thematic, inductive open coding performed independently by trained coders, with final codes reached by group consensus., Results: We conducted 6 focus groups of 3 to 5 participants each and 1 individual interview, with 24 total parents. We identified the following themes: 1) "I just felt like we was a number": Black families perceived experiences that felt impersonal and lacked empathy; 2) "Why is the doctor treating me like I don't matter?": Black families perceived experiences with poor care and worse treatment; 3) Black families experience racism across socioecological levels when interacting with pediatric health systems; 4) Positive perceived experiences can guide improvement; and 5) Improvement will require antiracist efforts across the levels of racism., Conclusions: In this qualitative study, we found that Black families have had many poor pediatric experiences, perceive racism as affecting child health broadly across socioecological levels, and recommend a multidimensional antiracist approach to improvement. Our findings underscore the importance of elevating Black family voices in developing policies that prioritize antiracism and work to eliminate the harmful impacts of racism on child health., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Microbial communities offer vast potential across numerous sectors but remain challenging to systematically control. We develop a two-stage approach to guide the taxonomic composition of synthetic microbiomes by precisely manipulating media components and initial species abundances. By combining high-throughput experiments and computational modeling, we demonstrate the ability to predict and design the diversity of a 10-member synthetic human gut community. We reveal that critical environmental factors governing monoculture growth can be leveraged to steer microbial communities to desired states. Furthermore, systematically varied initial abundances drive variation in community assembly and enable inference of pairwise inter-species interactions via a dynamic ecological model. These interactions are overall consistent with conditioned media experiments, demonstrating that specific perturbations to a high-richness community can provide rich information for building dynamic ecological models. This model is subsequently used to design low-richness communities that display low or high temporal taxonomic variability over an extended period. A record of this paper's transparent peer review process is included in the supplemental information., Competing Interests: Declaration of interests B.M.C., O.S.V., and B.F.P. are inventors on a provisional patent application filed by the Wisconsin Alumni Research Foundation (WARF) with the US Patent and Trademark Office, which describes and claims concepts disclosed herein (application no. 63/306,691 Filing Date: 2/4/2022)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

There have been recent calls for the use of artemisinin-based combination therapies (ACTs) for uncomplicated malaria in the first trimester of pregnancy. Nevertheless, the 2021 WHO Guidelines for Malaria reaffirmed their position that there is not adequate clinical safety data on artemisinins to support that usage. The WHO's position is consistent with several issues with the existing clinical data. First, first trimester safety results from multiple ACTs were lumped in a meta-analysis which does not demonstrate that each of the included ACTs is equally safe. Second, safety results from all periods of the first trimester were lumped in the meta-analysis which does not demonstrate the same level of safety for all subperiods, particularly gestational Weeks 6-8 which is likely to be the most sensitive period. Third, even if there is evidence of a lack of an effect on miscarriage rate for a particular ACT, it does not follow then there are no developmental effects for any ACT. In monkeys, artesunate caused marked embryonal anemia leading to embryo death but the long-term consequences of lower levels of embryonal anemia are not known. Fourth, there have been advances in the sensitivity and usage of rapid diagnostic tests that will lead to diagnoses of malaria earlier in gestation which is less well studied and more likely sensitive to artemisinins. Any clinical studies of the safety of ACTs in the first trimester need to evaluate the results of treatment with individual ACTs during different 1- to 2-week periods of the first trimester., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Predicting the dynamics and functions of microbiomes constructed from the bottom-up is a key challenge in exploiting them to our benefit. Current models based on ecological theory fail to capture complex community behaviors due to higher order interactions, do not scale well with increasing complexity and in considering multiple functions. We develop and apply a long short-term memory (LSTM) framework to advance our understanding of community assembly and health-relevant metabolite production using a synthetic human gut community. A mainstay of recurrent neural networks, the LSTM learns a high dimensional data-driven non-linear dynamical system model. We show that the LSTM model can outperform the widely used generalized Lotka-Volterra model based on ecological theory. We build methods to decipher microbe-microbe and microbe-metabolite interactions from an otherwise black-box model. These methods highlight that Actinobacteria, Firmicutes and Proteobacteria are significant drivers of metabolite production whereas Bacteroides shape community dynamics. We use the LSTM model to navigate a large multidimensional functional landscape to design communities with unique health-relevant metabolite profiles and temporal behaviors. In sum, the accuracy of the LSTM model can be exploited for experimental planning and to guide the design of synthetic microbiomes with target dynamic functions., Competing Interests: MB, ZS, OV The authors declare no conflicts of interest, RC, JT, AH No competing interests declared, (© 2022, Baranwal, Clark et al.)

Oxygen levels in vivo are autonomously regulated by a supply-demand balance, which can be altered in disease states. However, the oxygen levels of in vitro cell culture systems, particularly microscale cell culture, are typically dominated by either supply or demand. Further, the oxygen microenvironment in these systems is rarely monitored or reported. Here, a method to establish and dynamically monitor autonomously regulated oxygen microenvironments (AROM) using an oil overlay in an open microscale cell culture system is presented. Using this method, the oxygen microenvironment is dynamically regulated via the supply-demand balance of the system. Numerical simulation and experimental validation of oxygen transport within multi-liquid-phase, microscale culture systems involving a variety of cell types, including mammalian, fungal, and bacterial cells are presented. Finally, AROM is applied to establish a coculture between cells with disparate oxygen demands-primary intestinal epithelial cells (oxygen consuming) and Bacteroides uniformis (an anaerobic species prevalent in the human gut)., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

The capability to design microbiomes with predictable functions would enable new technologies for applications in health, agriculture, and bioprocessing. Towards this goal, we develop a model-guided approach to design synthetic human gut microbiomes for production of the health-relevant metabolite butyrate. Our data-driven model quantifies microbial interactions impacting growth and butyrate production separately, providing key insights into ecological mechanisms driving butyrate production. We use our model to explore a vast community design space using a design-test-learn cycle to identify high butyrate-producing communities. Our model can accurately predict community assembly and butyrate production across a wide range of species richness. Guided by the model, we identify constraints on butyrate production by high species richness and key molecular factors driving butyrate production, including hydrogen sulfide, environmental pH, and resource competition. In sum, our model-guided approach provides a flexible and generalizable framework for understanding and accurately predicting community assembly and metabolic functions.

The American population is aging and changes in the population's age structure are leading to an aging of the nation's workforce. In addition, changes to age-specific participation rates are exacerbating the aging of the national labor force. An important challenge for firms and organizations is how does workforce aging affect labor costs, productivity, and the sustainability of the organization. This article examines employer responses to workforce aging, including changes to retirement policies, modification in working conditions, adoption of phased retirement plans, and reforming other employee benefits., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Malaria is a particular problem in pregnancy because of enhanced sensitivity, the possibility of placental malaria, and adverse effects on pregnancy outcome. Artemisinin-containing combination therapies (ACTs) are the most effective antimalarials known. WHO recommends 7-day quinine therapy for uncomplicated Plasmodium falciparum malaria in the first trimester despite the superior tolerability and efficacy of 3-day ACT regimens because artemisinins caused embryolethality and/or cardiovascular malformations at relatively low doses in rats, rabbits, and monkeys. The developmental toxicity of artesunate, artemether, and DHA were similar in rats but artesunate was embryotoxic at lower doses in rabbits (5 mg/kg/day) than artemether (no effect level = 25 mg/kg/day). In clinical studies in Africa, treatment with artemether-lumefantrine in the first trimester was observed to be highly efficacious and the miscarriage rate (≤3.1%) was similar to no antimalarial treatment (2.6%). When data from the first-trimester use of largely artesunate-based therapies in Thailand were pooled together, there was no difference in miscarriage rate compared to quinine. However, individually, artesunate-mefloquine was associated with a higher miscarriage rate (15/71 = 21%) compared to other artemisinin-based therapies including 7-day artesunate + clindamycin (2/50 = 4%) and quinine (92/842 = 11%). Thus, appropriate statistical comparisons of individual ACT groups are needed prior to assuming that they all have the same risk for developmental toxicity. Current limitations in the assessment of the safety of ACTs in the first trimester are a lack of exposures early in gestation (gestational weeks 6-7), limited postnatal evaluation for cardiovascular malformations, and the pooling of all ACTs for the assessment of risk., (© 2020 Wiley Periodicals LLC.)

Medicine recognizes burnout as a threat to quality patient care and physician quality of life. This issue exists throughout medicine but is notably prevalent in emergency medicine (EM). Because the concept of "wellness" lacks a clear definition, attempts at ameliorating burnout that focus on achieving wellness make success difficult to achieve and measure. Recent work within the wellness literature suggests that the end goal should be to achieve a culture of wellness by addressing all aspects of the physician's environment. A review of the available literature on burnout and wellness interventions in all medical specialties reveals that interventions focusing on individual physicians have varying levels of success. Efforts to compare these interventions are hampered by a lack of consistent endpoints. Studies with consistent endpoints do not demonstrate clear benefits of achieving them because improving scores on various scales may not equate to improvement in quality of care or physician quality of life. Successful interventions have uncertain, long-term effects. Outside of EM, the most successful interventions focus on changes to systems rather than to individual physicians. Within EM, the number of well-structured interventions that have been studied is limited. Future work to achieve the desired culture of wellness within EM requires establishment of a consistent endpoint that serves as a surrogate for clinical significance, addressing contributors to burnout at all levels, and integrating successful interventions into the fabric of EM.

Microbial interactions are major drivers of microbial community dynamics and functions but remain challenging to identify because of limitations in parallel culturing and absolute abundance quantification of community members across environments and replicates. To this end, we developed Microbial Interaction Network Inference in microdroplets (MINI-Drop). Fluorescence microscopy coupled to computer vision techniques were used to rapidly determine the absolute abundance of each strain in hundreds to thousands of droplets per condition. We showed that MINI-Drop could accurately infer pairwise and higher-order interactions in synthetic consortia. We developed a stochastic model of community assembly to provide insight into the heterogeneity in community states across droplets. Finally, we elucidated the complex web of interactions linking antibiotics and different species in a synthetic consortium. In sum, we demonstrated a robust and generalizable method to infer microbial interaction networks by random encapsulation of sub-communities into microfluidic droplets., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Despite the many benefits of regular breakfast consumption few parents and children consume this meal every day and research examining the determinants of breakfast consumption is limited. Thus, the purpose of this study was to examine breakfast-related cognitions (i.e., beliefs, attitudes, facilitators, barriers) of parents and school-age children (ages 6-11 years) using the constructs of Social Cognitive Theory as a guide. Parents ( n = 37) and children ( n = 41) participated in focus group discussions held in community settings in 3 states (FL, NJ, WV). Data were qualitatively content analyzed to detect trends. Parents felt breakfast was important for numerous reasons. Parents expressed concern about the healthfulness of some traditional breakfast options, preferring breakfasts containing mostly fruits, vegetables, and protein and fewer carbohydrates. Parents identified lack of time as the greatest barrier to breakfast consumption. To overcome this barrier, they utilized grab-and-go foods, prepared breakfast ahead of time, and got up earlier. Utilizing the school breakfast program was another strategy mentioned, however some were concerned about the nutritional quality of this option. Children recognized the importance of breakfast and cited several benefits. The greatest barrier to breakfast identified by children was feeling rushed in the morning. To overcome barriers, children suggested having a morning routine, selecting or preparing breakfast foods ahead, and relying on parents to encourage breakfast consumption. The effectiveness of interventions aiming to improve breakfast intake may be improved by addressing parent and child breakfast-related cognitions and tailoring interventions to address their needs.

Malaria during pregnancy results in intrauterine growth restriction, fetal anemia, and infant mortality. Women are more susceptible to malaria during pregnancy due to malaria-induced inflammation and the sequestration of infected red blood cells in the placenta, which bind to the chondroitin sulfate portion of syndecan-1 on the syncytiotrophoblast and in the intervillous space. Syndecan-1 is a dimeric proteoglycan with an extracellular ectodomain that is cleaved from the transmembrane domain (referred to as "shedding") by matrix metalloproteinases (MMPs), likely the secreted MMP-9. The ectodomain includes four binding sites for chondroitin sulfate, which are proximal to the transmembrane domain, and six distal binding sites primarily for heparan sulfate. This "shedding" of syndecan-1 is inhibited by the presence of the heparan sulfate chains, which can be removed by heparanase. The intervillous space contains fibrin strands and syndecan-1 ectodomains free of heparan sulfate. The following is proposed as the sequence of events that leads to and is primarily responsible for sequestration in the intervillous space of the placenta. Inflammation associated with malaria triggers increased heparanase activity that degrades the heparan sulfate on the membrane-bound syndecan-1. Inflammation also upregulates MMP-9 and the removal of heparan sulfate gives MMP-9 access to cleave syndecan-1, thereby releasing dimeric syndecan-1 ectodomains with at least four chondroitin sulfate chains attached. These multivalent ectodomains bind infected RBCs together leading to their aggregation and entrapment in intervillous fibrin. This mechanism suggests possible new targets for anti-placental malaria drugs such as the inhibition of MMP-9. Doxycycline is an antimalarial drug which inhibits MMP-9., (© 2019 The Author. Birth Defects Research published by Wiley Periodicals, Inc.)

Background: Cost is a commonly reported barrier to healthy eating. This is a secondary research analysis designed to examine the food expenditures of young adults on a university campus following the United States Department of Agriculture (USDA) MyPlate guidelines for fruits and vegetables., Methods: Meal receipts and dietary intake were recorded weekly. Anthropometrics and clinical assessments were recorded before intervention. Researchers rated compliance based on the participant's dietary food log, receipt matching, food pictures, and reports during weekly 1-hour consultations., Results: Fifty-three young adults (18-30 years old) at-risk of, or diagnosed with, metabolic syndrome (MetS) were enrolled in the study, with 10 excluded ( n  = 43) from analyses due to enrollment in a fixed cost university campus dining meal plan. A two sample t -test assessed differences in food costs and regression analysis determined associations between food cost and diet compliance while controlling for confounding factors of age, sex, and body mass index (BMI). Diet compliant subjects ( n  = 38) had higher weekly food cost at $95.73 compared to noncompliant subjects ( n  = 5) who spent $66.24 ( p =0.01). A regression analysis controlling for age, sex, BMI, and geographical region also indicated cost differences based on diet compliance ( p < 0.0001)., Conclusion: Results indicate an ∼$29.00 per week increase in food cost when eating the recommended amount of fruit and vegetables. These findings can contribute to research incentive design, program planning cost, and determining effective interventions to improve diet in this population.

Study Objectives: To describe parents' and school-age children's sleep-related cognitions and behaviors., Methods: Parents (n = 36) and school-age children (n = 40; 6-11 years old) from New Jersey, Florida, and West Virginia participated in focus groups lasting ~60 minutes for parents and ~30 minutes for children. Trained researchers led the focus groups designed using Social Cognitive Theory constructs. Standard content analysis procedures were used independently by 3 trained researchers to analyze focus group data., Results: A consistent finding across focus groups was that a set bedtime was a typical behavior. Both parents and children recognized the importance of sleep for health and academic success. Technology was highlighted by both groups as a barrier to adequate sleep. The children discussed postbedtime activities of their parents as barriers to sleep. Physical activity along with several healthy sleep practices was identified as strategies to improve sleep. Parents and children stressed the role of parents in promoting healthy sleep behaviors and sleep-conducive environment. Participants did not mention some well-established links between sleep duration and health as well as sleep-promoting behaviors. Several unique factors, not yet reported in the literature, were discussed by the parents and children including the use of stuffed animals for comfort and disruptive behaviors of others in the household., Conclusions: Many of the cognitions of parents and children coincide with evidence from scientific literature surrounding sleep and sleep hygiene but also demonstrated sleep hygiene knowledge gaps. Study findings can be applied to future sleep education materials targeting parents and school-age children., (Copyright © 2018 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

The FRUVEDomics study investigates the effect of a diet intervention focused on increasing fruit and vegetable intake on the gut microbiome and cardiovascular health of young adults with/at risk for metabolic syndrome (MetS). It was hypothesized that the recommended diet would result in metabolic and gut microbiome changes. The 9-week dietary intervention adhered to the US Department of Agriculture Dietary Guidelines for Americans and focused on increasing fruit and vegetable intake to equal half of the diet. Seventeen eligible young adults with/or at high risk of MetS consented and completed preintervention and postintervention measurements, including anthropometric, body composition, cardiovascular, complete blood lipid panel, and collection of stool sample for microbial analysis. Participants attended weekly consultations to assess food logs, food receipts, and adherence to the diet. Following intention-to-treat guidelines, all 17 individuals were included in the dietary, clinical, and anthropometric analysis. Fruit and vegetable intake increased from 1.6 to 3.4 cups of fruits and vegetables (P < .001) daily. Total fiber (P = .02) and insoluble fiber (P < .0001) also increased. Clinical laboratory changes included an increase in sodium (P = .0006) and low-density lipoprotein cholesterol (P = .04). In the fecal microbiome, Erysipelotrichaceae (phylum Firmicutes) decreased (log2 fold change: -1.78, P = .01) and Caulobacteraceae (phylum Proteobacteria) increased (log2 fold change = 1.07, P = .01). Implementing a free-living 9-week diet, with intensive education and accountability, gave young adults at high risk for/or diagnosed with MetS the knowledge, skills, and feedback to improve diet. To yield greater impact, a longer diet intervention may be needed in this population., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease is the leading cause of mortality and morbidity globally. With widespread and growing use of smart phones and mobile devices, the use of mobile health (mHealth) in transmission of physiologic parameters and patient-referred symptoms to healthcare providers and researchers, as well as reminders and care plan applications from providers to patients, has potential to revolutionize both clinical care and the conduct of clinical trials with improved designs, data capture, and potentially lower costs. In randomized early phase proof-of-concept studies, focusing on lifestyle intervention, there is evidence that mHealth technology can improve outcomes. By contrast, results from small randomized controlled trials that tested mHealth interventions in heart failure patients were disappointing with inconsistent findings. These inconclusive results could be partially attributed to a lack of methodological rigor (insufficient sample size, quasi-experimental design, inadequate mHealth equipment). Therefore, there is an urgent need to develop systematic evidence-based guidelines and parameters for mHealth to be effectively utilized in cardiovascular clinical trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Within the last few decades, an increasing number of adults have sought orthodontic therapy. One disadvantage of pursuing orthodontic treatment in adulthood is the lengthened time span required to complete tooth movement. The purpose of this article is to review the biologic mechanisms of accelerated tooth movement as well as the literature on nonsurgical and surgical techniques that may reduce the duration of orthodontic treatment.

Background: Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials., Methods/design: The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred., Conclusions: GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Cyanobacteria are photosynthetic microorganisms whose metabolism can be modified through genetic engineering for production of a wide variety of molecules directly from CO 2 , light, and nutrients. Diverse molecules have been produced in small quantities by engineered cyanobacteria to demonstrate the feasibility of photosynthetic biorefineries. Consequently, there is interest in engineering these microorganisms to increase titer and productivity to meet industrial metrics. Unfortunately, differing experimental conditions and cultivation techniques confound comparisons of strains and metabolic engineering strategies. In this work, we discuss the factors governing photoautotrophic growth and demonstrate nutritionally replete conditions in which a model cyanobacterium can be grown to stationary phase with light as the sole limiting substrate. We introduce a mathematical framework for understanding the dynamics of growth and product secretion in light-limited cyanobacterial cultures. Using this framework, we demonstrate how cyanobacterial growth in differing experimental systems can be easily scaled by the volumetric photon delivery rate using the model organisms Synechococcus sp. strain PCC7002 and Synechococcus elongatus strain UTEX2973. We use this framework to predict scaled up growth and product secretion in 1L photobioreactors of two strains of Synechococcus PCC7002 engineered for production of l-lactate or L-lysine. The analytical framework developed in this work serves as a guide for future metabolic engineering studies of cyanobacteria to allow better comparison of experiments performed in different experimental systems and to further investigate the dynamics of growth and product secretion., (Copyright © 2018 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Background: Combination medicines including an artemisinin are the mainstay of antimalarial therapy. Artemisinins are potent embryotoxicants in animal species due to their trioxane moiety., Methods: As part of its development, the new synthetic trioxolane antimalarial artefenomel (OZ439) was tested in rat whole embryo culture and in rat embryo-fetal toxicity studies with dosing throughout organogenesis or with a single dose on Gestational Day (GD) 12. The single-dose studies included groups treated with artesunate to allow a direct comparison of the embryotoxicity of the two antimalarials and included toxicokinetics hematology and histological examination of embryos. In addition, the distribution of artefenomel-related material in plasma was determined after the administration of 14 C-artefenomel., Results: Artefenomel and artesunate showed similar patterns of embryotoxicity including cardiovascular defects and resorption with a steep dose-response. They both also caused a depletion of circulating embryonic erythroblasts both in vitro and in vivo and decreases in maternal reticulocyte count. However, artefenomel was ∼250-fold less potent than the active metabolite of artesunate (dihydroartemisinin) as an embryotoxicant in vitro. The safety margin (based on AUC) for artefenomel administered on GD 12 was approximately 100-fold greater than that for artesunate. Also, unlike artesunate, artefenomel was not a selective developmental toxicant., Conclusions: The lesser embryotoxicity of artefenomel is likely linked to its original design which included two blocking side groups that had been introduced to lower the reactivity with ferrous iron. Our data support the hypothesis that artefenomel's improved safety margin is linked to a lower potential for inhibiting heme biosynthesis in embryonic erythroblasts., (© 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.)

Microorganisms can catabolize a wide range of organic compounds and therefore have the potential to perform many industrially relevant bioconversions. One barrier to realizing the potential of biorefining strategies lies in our incomplete knowledge of metabolic pathways, including those that can be used to assimilate naturally abundant or easily generated feedstocks. For instance, levulinic acid (LA) is a carbon source that is readily obtainable as a dehydration product of lignocellulosic biomass and can serve as the sole carbon source for some bacteria. Yet, the genetics and structure of LA catabolism have remained unknown. Here, we report the identification and characterization of a seven-gene operon that enables LA catabolism in Pseudomonas putida KT2440. When the pathway was reconstituted with purified proteins, we observed the formation of four acyl-CoA intermediates, including a unique 4-phosphovaleryl-CoA and the previously observed 3-hydroxyvaleryl-CoA product. Using adaptive evolution, we obtained a mutant of Escherichia coli LS5218 with functional deletions of fadE and atoC that was capable of robust growth on LA when it expressed the five enzymes from the P. putida operon. This discovery will enable more efficient use of biomass hydrolysates and metabolic engineering to develop bioconversions using LA as a feedstock.