Objective: We sought to evaluate two approaches with varying time and complexity in engaging adolescents with an Internet-based preventive intervention for depression in primary care. We conducted a randomized controlled trial comparing primary care physician motivational interview (MI, 10–15 minutes) + Internet program versus brief advice (BA, 2–3 minutes) + Internet program. Setting: Adolescent primary care patients in the United States, ages 14–21. Participants: 83 individuals (40% non-white) at increased risk for depressive disorders (sub-threshold depressed mood > 3–4 weeks) were randomly assigned to either the MI group (n=43) or the BA group (n=40). Main Outcome Measures: Patient Health Questionnaire (PHQ-A) – Adolescent and Center for Epidemiologic Studies Depression Scale (CES-D). Results: Both groups substantially engaged the Internet site (MI, 90.7% versus BA 77.5%). For both groups, CES-D-10 scores declined (MI, 24.0 to 17.0 p < 0.001; BA, 25.2 to 15.5, p < 0.001). The percentage of those with clinically significant depression symptoms based on CES-D-10 scores declined in both groups from baseline to twelve weeks, (MI, 52% to 12%, p < 0.001; BA, 50% to 15%, p < 0.001). The MI group demonstrated declines in self-harm thoughts and hopelessness and was significantly less likely than the BA group to experience a depressive episode (4.65% versus 22.5%, p = 0.023) or to report hopelessness (MI group of 2% versus 15% for the BA group, p=0.044) by twelve weeks. Conclusions: An Internet-based prevention program in primary care is associated with declines in depressed mood and the likelihood of having clinical depression symptom levels in both groups. Motivational interviewing in combination with an Internet behavior change program may reduce the likelihood of experiencing a depressive episode and hopelessness.

Methanol is an attractive substrate for biological production of chemicals and fuels. Engineering methylotrophic Escherichia coli as a platform organism for converting methanol to metabolites is desirable. Prior efforts to engineer methylotrophic E. coli were limited by methanol dehydrogenases (Mdhs) with unfavorable enzyme kinetics. We engineered E. coli to utilize methanol using a superior NAD-dependent Mdh from Bacillus stearothermophilus and ribulose monophosphate (RuMP) pathway enzymes from B. methanolicus. Using C-labeling, we demonstrate this E. coli strain converts methanol into biomass components. For example, the key TCA cycle intermediates, succinate and malate, exhibit labeling up to 39%, while the lower glycolytic intermediate, 3-phosphoglycerate, up to 53%. Multiple carbons are labeled for each compound, demonstrating a cycling RuMP pathway for methanol assimilation to support growth. By incorporating the pathway to synthesize the flavanone naringenin, we demonstrate the first example of in vivo conversion of methanol into a specialty chemical in E. coli.

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Fermentation-based chemical production strategies provide a feasible route for the rapid, safe, and sustainable production of a wide variety of important chemical products, ranging from fuels to pharmaceuticals. These strategies have yet to find wide industrial utilization due to their inability to economically compete with traditional extraction and chemical production methods. Here, we engineer for the first time the complex microbial biosynthesis of an anthocyanin plant natural product, starting from sugar. This was accomplished through the development of a synthetic, 4-strain Escherichia coli polyculture collectively expressing 15 exogenous or modified pathway enzymes from diverse plants and other microbes. This synthetic consortium-based approach enables the functional expression and connection of lengthy pathways while effectively managing the accompanying metabolic burden. The de novo production of specific anthocyanin molecules, such as calistephin, has been an elusive metabolic engineering target for over a decade. The utilization of our polyculture strategy affords milligram-per-liter production titers. This study also lays the groundwork for significant advances in strain and process design toward the development of cost-competitive biochemical production hosts through nontraditional methodologies.

Routine use of Masimo SET pulse oximetry in the NICU could improve clinician confidence in the parameter leading to more judicious titration of oxygen with possible reductions in hypoxic (e.g., pulmonary hypertension) and hyperoxic (e.g., retinopathy of prematurity) pathology. Additionally, a more trustworthy technology should equate with fewer confirmatory arterial blood gas analyses (less blood loss), and faster weaning from the mechanical ventilation (less chronic lung disease).