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Ketamine, a noncompetitive NMDA receptor antagonist, has been exclusively used as an anesthetic in medicine and has led to new insights into the pathophysiology of neuropsychiatric disorders. Clinical studies have shown that low subanesthetic doses of ketamine produce antidepressant effects for individuals with depression. However, its use as a treatment for psychiatric disorders has been limited due to its reinforcing effects and high potential for diversion and misuse. Preclinical studies have focused on understanding the molecular mechanisms underlying ketamine’s antidepressant effects, but a precise mechanism had yet to be elucidated. Here we review different hypotheses for ketamine’s mechanism of action including the direct inhibition and disinhibition of NMDA receptors, AMPAR activation, and heightened activation of monoaminergic systems. The proposed mechanisms are not mutually exclusive, and their combined influence may exert the observed structural and functional neural impairments. Long term use of ketamine induces brain structural, functional impairments, and neurodevelopmental effects in both rodents and humans. Its misuse has increased rapidly in the past 20 years and is one of the most common addictive drugs used in Asia. The proposed mechanisms of action and supporting neuroimaging data allow for the development of tools to identify ‘biotypes’ of ketamine use disorder (KUD) using machine learning approaches, which could inform intervention and treatment.

Side effects of medications for opioid use disorder (MOUD) such as weight gain contribute to their stigma. Substantial evidence suggests that women have a more severe side effect profile to MOUD than men, and concerns about weight gain during treatment are prevalent. However, the few studies reporting sex differences in weight gain during treatment show conflicting results and are restricted to methadone. In addition, little is known about possible sex differences in weight gain to buprenorphine, which is the most commonly prescribed MOUD in the United States.To address these issues, we performed a systematic review and meta-analysis on the few studies reporting longitudinal data on sex differences in body mass index (BMI) gain during methadone treatment (Study 1). In a separate study, we also re-analyzed data from trial CTN-0030 of the National Institute on Drug Abuse Clinical Trial Network (NIDA CTN), which involved a 12-week buprenorphine treatment regimen (Study 2; n = 360; 209 Male, 151 Female).For Study 1, across all papers reporting longitudinal data (k = 4, n = 362 OUD patients), there were BMI increases that ranged from 2.2 to 5.4 BMI after at least one year of methadone treatment, but there were no significant sex differences in BMI increases (Standardized Mean Difference, FemaleMale = 0.352, SE =0.270; 95 % CI = [-0.18 0.88]; p = .193). Study 2 showed no significant differences in weight before and after 12 weeks of buprenorphine treatment nor did it show sex differences in weight change with treatment (β = 2.34, p = .511).These analyses corroborate evidence of weight gain with methadone treatment but did not observe a sex-based disparity in weight gain with methadone or buprenorphine treatment for OUD.

Dopamine facilitates cognition and is implicated in reward processing. Methylphenidate, a dopamine enhancing medication widely used to treat attention-deficit/hyperactivity disorder, has rewarding and addictive effects if injected. Since methylphenidate’s brain uptake is much faster when injected than when taken orally, we hypothesized that the amplitude and the speed of dopamine release in striatum would underly drug reward. To test this hypothesis we developed a non-invasive method to assess methylphenidate-related extracellular dopamine increases at 1-minute temporal resolution using positron emission tomography, which we validated in preclinical microdialysis data. Using a placebo-controlled double-blind within-subjects design, we show in 20 healthy controls that striatal dopamine increases induced by intravenous methylphenidate (0.25 mg/kg) were significantly faster than those induced by oral methylphenidate (60 mg) and that the time-to-peak of dopamine release was strongly associated with the intensity of self-reports of feeling “high”. With this novel approach we show for the first time in humans that stronger drug reward is associated with shorter dopamine time-to-peak after methylphenidate administration.

Background and Objectives: Recruitment of underrepresented minorities (URM) in medicine has risen to the forefront as a strategy to address health inequities, but the experiences of URM residents within their own programs are poorly understood. We describe the development and implementation of a diversity, equity, and inclusion (DEI) climate survey at our residency program, the results of which have informed our DEI efforts. Methods: A resident-faculty work group collaboratively developed an 81-item questionnaire, informed by other institutional climate surveys. We administered the survey annually from 2018 through 2021 to all residents and faculty at our large academic family medicine residency program. The anonymous survey covered six key areas: general climate, climate for specific group, personal experience with discrimination and harassment, recruitment, burnout, and curriculum. Results: Average response rates were 84% and 50% for residents and faculty, respectively. Survey results show low satisfaction with resident and faculty diversity; higher rates of burnout for respondents who self-identify as URM, persons of color (POC), and/or LGBTQ; and racial and gender differences in experiences of workplace discrimination and sexual harassment. Conclusions: Instituting an annual internal climate survey at our residency has provided invaluable information regarding the perspectives and experiences of our residents and faculty that has informed our DEI initiatives. We envision that our survey will inform continual improvement and serve as a model for similar introspection leading to meaningful action at other programs.

Agricultural productivity relies on synthetic nitrogen fertilizers, yet half of that reactive nitrogen is lost to the environment. There is an urgent need for alternative nitrogen solutions to reduce the water pollution, ozone depletion, atmospheric particulate formation, and global greenhouse gas emissions associated with synthetic nitrogen fertilizer use. One such solution is biological nitrogen fixation (BNF), a component of the complex natural nitrogen cycle. BNF application to commercial agriculture is currently limited by fertilizer use and plant type. This paper describes the identification, development, and deployment of the first microbial product optimized using synthetic biology tools to enable BNF for corn (Zea mays) in fertilized fields, demonstrating the successful, safe commercialization of root-associated diazotrophs and realizing the potential of BNF to replace and reduce synthetic nitrogen fertilizer use in production agriculture. Derived from a wild nitrogen-fixing microbe isolated from agricultural soils, Klebsiella variicola 137-1036 ("Kv137-1036") retains the capacity of the parent strain to colonize corn roots while increasing nitrogen fixation activity 122-fold in nitrogen-rich environments. This technical milestone was then commercialized in less than half of the time of a traditional biological product, with robust biosafety evaluations and product formulations contributing to consumer confidence and ease of use. Tested in multi-year, multi-site field trial experiments throughout the U.S. Corn Belt, fields grown with Kv137-1036 exhibited both higher yields (0.35 ± 0.092 t/ha ± SE or 5.2 ± 1.4 bushels/acre ± SE) and reduced within-field yield variance by 25% in 2018 and 8% in 2019 compared to fields fertilized with synthetic nitrogen fertilizers alone. These results demonstrate the capacity of a broad-acre BNF product to fix nitrogen for corn in field conditions with reliable agronomic benefits.

BACKGROUND Multi-level interventions are necessary to address the complex social contributors to health that limit Black women’s uptake of PrEP, including medical distrust, PrEP stigma, and access to equitable health care. Strategies to improve knowledge, awareness, and uptake of PrEP among Black women will be more successful if they are informed by Black women and their communities and implemented within trusted environments. Providing women with information through trusted cultural and social channels can effectively support informed decision making about PrEP for themselves and members of their social networks who are eligible for PrEP. OBJECTIVE This multilevel, mixed-methods study uses a community-engagement approach to develop and pilot test a salon-based intervention with the goal of improving knowledge and awareness of PrEP as well as PrEP stigma and uptake. METHODS There are three components of this intervention: (1) stylist training, (2) women-focused entertainment videos and modules, and (3) engagement of PrEP Navigator. First, stylist training will be provided virtually through two 2-hour training sessions delivered over two consecutive weeks. We will use a pre-post test design to examine knowledge and awareness improvement of PrEP among stylists. Upon full completion of training, stylists will receive a certificate of completion and “Ask Me about PrEP” signage for their beauty salons. Second, together with the community, we have co-developed a 4-part entertainment series (The Wright Place) that uses culturally and socially relevant stories to highlight key messages about (a) HIV, (b) PrEP, and (c) Black women’s social contributors to health. Quantitative measures will be used in a pre-post test design to examine PrEP knowledge, awareness, risk, stigma, trust, and intentions. Qualitative data will be collected to examine women’s perceptions of the usability and acceptability of the overall intervention and its implementation strategies. A video blog and educational modules providing resources and links about PrEP will be provided after each video. Third, participants will have access through an email or text message link to a PrEP Navigator who will respond to them privately to answer any questions or make referrals for PrEP as requested. RESULTS This project was funded in October 2020 by Gilead Sciences, Inc. and approved by the institutional review board in April 2021. Data collection of Phase 1 will begin October 2021. Data collection for Phase 2 will begin November 2021, with study completion by October 2022. CONCLUSIONS Multilevel interventions that consider the assets of the community have promise for promoting health among Black women who have influence within their social networks but may have low perceptions of risk. The findings of this study have the potential to be generalizable to other populations.

Experimental data about gene functions curated from the primary literature have enormous value for research scientists in understanding biology. Using the Gene Ontology (GO), manual curation by experts has provided an important resource for studying gene function, especially within model organisms. Unprecedented expansion of the scientific literature and validation of the predicted proteins have increased both data value and the challenges of keeping pace. Capturing literature-based functional annotations is limited by the ability of biocurators to handle the massive and rapidly growing scientific literature. Within the community-oriented wiki framework for GO annotation called the Gene Ontology Normal Usage Tracking System (GONUTS), we describe an approach to expand biocuration through crowdsourcing with undergraduates. This multiplies the number of high-quality annotations in international databases, enriches our coverage of the literature on normal gene function, and pushes the field in new directions. From an intercollegiate competition judged by experienced biocurators, Community Assessment of Community Annotation with Ontologies (CACAO), we have contributed nearly 5,000 literature-based annotations. Many of those annotations are to organisms not currently well-represented within GO. Over a 10-year history, our community contributors have spurred changes to the ontology not traditionally covered by professional biocurators. The CACAO principle of relying on community members to participate in and shape the future of biocuration in GO is a powerful and scalable model used to promote the scientific enterprise. It also provides undergraduate students with a unique and enriching introduction to critical reading of primary literature and acquisition of marketable skills., Author summary The primary scientific literature catalogs the results from publicly funded scientific research about gene function in human-readable format. Information captured from those studies in a widely adopted, machine-readable standard format comes in the form of Gene Ontology (GO) annotations about gene functions from all domains of life. Manual annotations based on inferences directly from the scientific literature, including the evidence used to make such inferences, represent the best return on investment by improving data accessibility across the biological sciences and allowing novel insights between evolutionarily related organisms. To supplement professional curation, our Community Assessment of Community Annotation with Ontologies (CACAO) project enabled annotation of the scientific literature by community annotators, in this case undergraduates, which resulted in the contribution of thousands of unique, validated entries to public resources. Importantly, the annotations described here initiated by nonexperts often deal with topics not typically covered by the experts. These annotations are now being used by scientists worldwide in their research efforts.

Here, we report genome sequences of 10 Bacillus cereus group-infecting bacteriophages. Each virus was isolated from an environmental sample, contained a double-stranded DNA genome, and belonged to the Myoviridae family. Nine phages exhibit a conserved genome structure, and one phage appears novel in genome structure, sequence, and protein content.

Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [

Summary Background Survival among children with high-risk solid tumors remains poor. Reprogrammed metabolism promotes tumor growth and may contain therapeutic liabilities. Tumor metabolism has been assessed in adults using intra-operative 13C-glucose infusions. Pediatric tumors differ from adult cancers in their low mutational burden and derivation from embryonic tissues. Here, we used 13C infusions to examine tumor metabolism in children, comparing phenotypes among tumor types and between childhood and adult cancers. Methods Patients recruited to the clinical trial NCT03686566 received an intra-operative infusion of [U-13C]glucose during tumor resection to evaluate central carbon pathways in the tumor, with concurrent metabolomics to provide a broad overview of metabolism. Differential characteristics were determined using multiple comparison tests and mixed-effect analyses. Findings We studied 23 tumors from 22 patients. All of the tumors analyzed by [U-13C]glucose contained labeling in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Labeling in the TCA cycle indicated the activity of pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC), with PDH predominating. Neuroblastomas had high lactate labeling relative to other childhood cancers and lung cancer and were distinguished by abundant tyrosine catabolites consistent with catecholamine synthesis. Conclusions Intra-operative [U13C]glucose infusions are safe and informative in pediatric cancer. Tumors of various histologies use glycolysis and oxidative metabolism, with subtype-selective differences evident from this small cohort. Expanding this cohort may uncover predictive biomarkers and therapeutic targets from tumor metabolism. Funding National Cancer Institute (NCI) grants to P.L. ( R21CA220090-01A1 ), R.J.D. ( R35CA22044901 ), and B.F. ( K99CA237724 ); Howard Hughes Medical Institute (HHMI), the 1 Million 4 Anna Foundation , and the Robert L. Moody Sr. Faculty Scholar Award funding to R.J.D.; Children’s Clinical Research Advisory Committee funding to K.J.; and Leopoldina Fellowship ( LPDS 2016-16 ) from the German National Academy of Sciences and Fritz Thyssen Foundation funding to A.T .

Although cerebral palsy is reported to have a higher prevalence in low-resource settings, there are few studies describing risk factors for cerebral palsy in these settings. A better understanding of the unique risk factors affecting children with cerebral palsy in low-resource settings could optimize both resource allocation and preventative strategies.A case-control study comparing children with cerebral palsy at ages two to 18 years with age-matched healthy control subjects was conducted between 2013 and 2014 at a referral center in Gaborone, Botswana. Study participants were enrolled from inpatient and outpatient settings, and data were collected through caregiver interviews, review of medical records, and physical examination of subjects. Risk factors were evaluated using conditional logistic regression models.We studied 56 subjects with cerebral palsy and 56 age-matched control subjects. Significant risk factors for cerebral palsy included a history of serious neonatal infection (odds ratio 15.0, P = 0.009), complications during delivery (odds ratio 13.5, P 0.001), and maternal human immunodeficiency virus (HIV) infection (odds ratio 3.5, P = 0.03). Maternal HIV infection remained a significant risk factor after adjusting for potential confounders and covariates (adjusted odds ratio 13.2, P = 0.05).Major risk factors for cerebral palsy in Botswana differ from those described in high-resource settings. Modifiable risk factors such as maternal HIV infection should be targeted as a potential strategy to reduce the incidence of cerebral palsy in Botswana. Further studies are necessary to determine optimal preventative and treatment strategies in this population.

Background Inadequately controlled anxiety during medical procedures is often remembered by children manifesting in distress, post-procedural behavior changes and overall angst. The use of distraction techniques during medical procedures has been shown to reduce distress and overall anxiety. We sought to evaluate the anxiety of children/parents with and without the use of a hand-held video game for distraction during transitions in the perioperative suite in a low risk outpatient pediatric surgical setting. Methods Children (n=108), between the ages of three and ten years undergoing low-risk outpatient surgical procedures were randomized and evaluated for anxiety without (n=53) and with (n=55) the use of a handheld video game in the preoperative suite. Clinical staff observed metrics associated with anxiety at three time points up to induction. A self-reported questionnaire evaluating typical parental anxiety and their anxiety around their child's surgical procedure was completed by parents after separation. Post-operative behavioral changes were queried 48 hours, 7-days and 14-days post-procedure through phone calls to parents. Results No significant differences in demographics or comorbidities between children that had the game for distraction and those that did not were identified in our cohort. Only ADHD was found to be significantly different between the randomized groups (no game; p=0.05). Overall, while not significant, a greater mean anxiety was noted in the NG group (p=0.36); specifically, the NG group had greater mean anxiety for the separation/preoperative (p=0.05) surveys, particularly in the ‘activity’, ‘emotional expressivity’ categories. Overall, separation was found to be significantly improved with hand held video game use; parental satisfaction was also increased in the group in which games were used. Conclusion The use of hand-held games in perioperative settings are a low-cost, safe, easy to implement method to mitigate pediatric/parental anxiety in an effort to improve overall satisfaction.

Mycobacteriophage are viruses that infect mycobacteria. More than 1,400 mycobacteriophage genomes have been sequenced, coding for over one hundred thousand proteins of unknown functions. Here we investigate mycobacteriophage Giles-host protein-protein interactions (PPIs) using yeast two-hybrid screening (Y2H). A total of 25 reproducible PPIs were found for a selected set of 10 Giles proteins, including a putative virion assembly protein (gp17), the phage integrase (gp29), the endolysin (gp31), the phage repressor (gp47), and six proteins of unknown function (gp34, gp35, gp54, gp56, gp64, and gp65). We note that overexpression of the proteins is toxic to M. smegmatis, although whether this toxicity and the associated changes in cellular morphology are related to the putative interactions revealed in the Y2H screen is unclear. ispartof: Scientific Reports vol:7 issue:1 pages:16514- ispartof: location:England status: published

An ultrasound-guided peripheral intravenous (UGPIV) quality improvement project occurred in an 849-bed tertiary care hospital with a goal to reduce the use of central lines, in particular, peripherally inserted central catheters (PICCs). Since implementation, PICCs have decreased by 46.7% overall, and 59 nurses in-hospital are competent in placing UGPIVs. Placement of UGPIVs by the bedside nurse is a key initiative in decreasing PICC use and, potentially, infections.

Children with cerebral palsy in low-resource settings are at high risk of malnutrition, which further increases their risk of poor health outcomes. However, there are few available data on specific risk factors for malnutrition among children with cerebral palsy in the developing world.We performed a case-control study among children with cerebral palsy receiving care at a tertiary care hospital in Gaborone, Botswana. Children with cerebral palsy and malnutrition were identified according to World Health Organization growth curves and compared with subjects with cerebral palsy without malnutrition. Risk factors for malnutrition were identified using multivariable logistic regression models. These risk factors were then used to generate a Malnutrition Risk Score, and Receiver Operating Characteristic curves were used to identify optimal cutoffs to identify subjects at high risk of malnutrition.We identified 61 children with cerebral palsy, 26 of whom (43%) met criteria for malnutrition. Nonambulatory status (odds ratio 13.8, 95% confidence interval [CI] 3.8-50.1, P 0.001) and a composite measure of socioeconomic status (odds ratio 1.6, 95% CI 1.0-2.5, P = 0.03) were the strongest risk factors for malnutrition. A Malnutrition Risk Score was constructed based on these risk factors, and receiver operating characteristic curve analysis demonstrated excellent performance characteristics of this score (area under the curve 0.92, 95% CI 0.89-0.94).Malnutrition is common among children with cerebral palsy in Botswana, and a simple risk score may help identify children with the highest risk. Further studies are needed to validate this screening tool and to determine optimal nutritional interventions in this population.

We report here the genome sequences of two novel Bacillus cereus group-infecting bacteriophages, Janet and OTooleKemple52. These bacteriophages are double-stranded DNA-containing Myoviridae isolated from soil samples. While their genomes share a high degree of sequence identity with one another, their host preferences are unique.

Mycobacteriophages are viruses that infect mycobacterial hosts and are prevalent in the environment. Nearly 700 mycobacteriophage genomes have been completely sequenced, revealing considerable diversity and genetic novelty. Here, we have determined the protein complement of mycobacteriophage Giles by mass spectrometry and mapped its genome-wide protein interactome to help elucidate the roles of its 77 predicted proteins, 50% of which have no known function. About 22,000 individual yeast two-hybrid (Y2H) tests with four different Y2H vectors, followed by filtering and retest screens, resulted in 324 reproducible protein-protein interactions, including 171 (136 nonredundant) high-confidence interactions. The complete set of high-confidence interactions among Giles proteins reveals new mechanistic details and predicts functions for unknown proteins. The Giles interactome is the first for any mycobacteriophage and one of just five known phage interactomes so far. Our results will help in understanding mycobacteriophage biology and aid in development of new genetic and therapeutic tools to understand Mycobacterium tuberculosis . IMPORTANCE Mycobacterium tuberculosis causes over 9 million new cases of tuberculosis each year. Mycobacteriophages, viruses of mycobacterial hosts, hold considerable potential to understand phage diversity, evolution, and mycobacterial biology, aiding in the development of therapeutic tools to control mycobacterial infections. The mycobacteriophage Giles protein-protein interaction network allows us to predict functions for unknown proteins and shed light on major biological processes in phage biology. For example, Giles gp76, a protein of unknown function, is found to associate with phage packaging and maturation. The functions of mycobacteriophage-derived proteins may suggest novel therapeutic approaches for tuberculosis. Our ORFeome clone set of Giles proteins and the interactome data will be useful resources for phage interactomics.

Background Cerebral palsy (CP) is the most common motor disability worldwide with an incidence of 2.5 per 1,000 births globally. Health beliefs among caregivers may be major drivers of health-related behaviours and service utilization, but little is known regarding health beliefs around CP in Africa. Methods Between July 2013 and September 2015, children with CP were identified in Gaborone, Botswana, and their caregivers were invited to participate in a qualitative study utilizing semistructured in-person one-on-one interviews. Interview questions addressed their understanding of CP, challenges of caring for a handicapped child, and community response to children with CP. Results Sixty-two caregivers participated in the study. Common themes elicited were variable knowledge about CP, financial and physical burden, lack of therapies and educational resources, and the impact of stigma. Caregivers in Botswana generally subscribed to a biomedical explanation of CP but expressed concerns regarding more stigmatizing folks beliefs expressed in the community. Conclusion Health beliefs regarding CP in Botswana likely have a significant impact on utilization of healthcare resources. Information from this study should inform future educational interventions for caregivers of children with CP.

We report the sequences of nine novel Bacillus cereus group bacteriophages: DIGNKC, Juglone, Nemo, Nigalana, NotTheCreek, Phrodo, SageFayge, Vinny, and Zuko. These bacteriophages are double-stranded DNA-containing Myoviridae isolated from soil samples using B. thuringiensis subsp. kurstaki as the host bacterium.

Three Bacillus bacteriophage-derived endolysins, designated PlyP56, PlyN74, and PlyTB40, were identified, cloned, purified, and characterized for their antimicrobial properties. Sequence alignment reveals these endolysins have an N-terminal enzymatically active domain (EAD) linked to a C-terminal cell wall binding domain (CBD). PlyP56 has a Peptidase_M15_4/VanY superfamily EAD with a conserved metal binding motif and displays biological dependence on divalent ions for activity. In contrast, PlyN74 and PlyTB40 have T7 lysozyme-type Amidase_2 and carboxypeptidase T-type Amidase_3 EADs, respectively, which are members of the MurNAc-LAA superfamily, but are not homologs and thus do not have a shared protein fold. All three endolysins contain similar SH3-family CBDs. Although minor host range differences were noted, all three endolysins show relatively broad antimicrobial activity against members of the Bacillus cereus sensu lato group with the highest lytic activity against B. cereus ATCC 4342. Characterization studies determined the optimal lytic activity for these enzymes was at physiological pH (pH 7.0–8.0), over a broad temperature range (4–55 °C), and at low concentrations of NaCl (

Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been taken by over 4,800 students at 73 institutions. We show here that this alliance-sourced model not only substantially advances the field of phage genomics but also stimulates students’ interest in science, positively influences academic achievement, and enhances persistence in science, technology, engineering, and mathematics (STEM) disciplines. Broad application of this model by integrating other research areas with large numbers of early-career undergraduate students has the potential to be transformative in science education and research training., IMPORTANCE Engagement of undergraduate students in scientific research at early stages in their careers presents an opportunity to excite students about science, technology, engineering, and mathematics (STEM) disciplines and promote continued interests in these areas. Many excellent course-based undergraduate research experiences have been developed, but scaling these to a broader impact with larger numbers of students is challenging. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunting Advancing Genomics and Evolutionary Science (SEA-PHAGES) program takes advantage of the huge size and diversity of the bacteriophage population to engage students in discovery of new viruses, genome annotation, and comparative genomics, with strong impacts on bacteriophage research, increased persistence in STEM fields, and student self-identification with learning gains, motivation, attitude, and career aspirations.

Rare spring blooms, >20μgl−1 chlorophyll a, were observed in the San Francisco Bay Delta during the drought year of 2014 in both the upper Sacramento River and in Suisun Bay. The upper Sacramento River bloom was dominated by chlorophytes, but biomass and photosynthetic efficiency (based on variable fluorescence, Fv/Fm) precipitously declined downstream when cells were exposed to sewage effluent and NH4+ levels>70μM-N. Further downriver, substantial rates of nitrification occurred, based on increasing levels of NO3− and NO2− in proportion to decreasing NH4+ concentrations, reducing NH4+ levels to 400μM-N, PO43−>13μM-P, but NH4+~2μM-N), very low chlorophyll a levels (~3μgL−1) and low Fv/Fm values, but elevated bacterial production, suggesting presence of an algal inhibitor, possibly an herbicide. Both rivers converge above Suisun Bay, where elevated NO3− (>50μM-N), sufficient PO43− (>3μM-P), and reduced NH4+ levels (as low as 6μM-N), and reduced flow created conditions conducive to a spatially large and physiologically healthy (elevated Fv/Fm) diatom bloom dominated by the species Entomoneis sp. We conceptualize this bloom as a “window of opportunity” response by these diatoms to multiple factors promoted by the drought, including longer residence time for cell growth and biomass accumulation, and longer time for in-river nitrification to occur, reducing sewage-derived NH4+ to a level where diatoms could access NO3− for uptake and growth. We suggest that management practices that favor higher rates of flow may narrow the “window of opportunity” for phytoplankton growth, potentially leading to low productivity and food limitation for fish. Under high flow, a condition of “washout” may develop where both chlorophyll and unassimilated nutrients are transported out of the bay, and the phytoplankton that do develop are less favorable in terms of community composition for supporting the upper food web.