Harnessing the Power of Generative AI for Clinical Summaries: Perspectives From Emergency Physicians.

STUDY OBJECTIVE: The workload of clinical documentation contributes to health care costs and professional burnout. The advent of generative artificial intelligence language models presents a promising solution. The perspective of clinicians may contribute to effective and responsible implementation of such tools. This study sought to evaluate 3 uses for generative artificial intelligence for clinical documentation in pediatric emergency medicine, measuring time savings, effort reduction, and physician attitudes and identifying potential risks and barriers. METHODS: This mixed-methods study was performed with 10 pediatric emergency medicine attending physicians from a single pediatric emergency department. Participants were asked to write a supervisory note for 4 clinical scenarios, with varying levels of complexity, twice without any assistance and twice with the assistance of ChatGPT Version 4.0. Participants evaluated 2 additional ChatGPT-generated clinical summaries: a structured handoff and a visit summary for a family written at an 8th grade reading level. Finally, a semistructured interview was performed to assess physicians' perspective on the use of ChatGPT in pediatric emergency medicine. Main outcomes and measures included between subjects' comparisons of the effort and time taken to complete the supervisory note with and without ChatGPT assistance. Effort was measured using a self-reported Likert scale of 0 to 10. Physicians' scoring of and attitude toward the ChatGPT-generated summaries were measured using a 0 to 10 Likert scale and open-ended questions. Summaries were scored for completeness, accuracy, efficiency, readability, and overall satisfaction. A thematic analysis was performed to analyze the content of the open-ended questions and to identify key themes. RESULTS: ChatGPT yielded a 40% reduction in time and a 33% decrease in effort for supervisory notes in intricate cases, with no discernible effect on simpler notes. ChatGPT-generated summaries for structured handoffs and family letters were highly rated, ranging from 7.0 to 9.0 out of 10, and most participants favored their inclusion in clinical practice. However, there were several critical reservations, out of which a set of general recommendations for applying ChatGPT to clinical summaries was formulated. CONCLUSION: Pediatric emergency medicine attendings in our study perceived that ChatGPT can deliver high-quality summaries while saving time and effort in many scenarios, but not all.

Usability Testing Via Simulation: Optimizing the NEAR4PEM Preintubation Checklist With a Human Factors Approach.

OBJECTIVES: To inform development of a preintubation checklist for pediatric emergency departments via multicenter usability testing of a prototype checklist. METHODS: This was a prospective, mixed methods study across 7 sites in the National Emergency Airway Registry for Pediatric Emergency Medicine (NEAR4PEM) collaborative. Pediatric emergency medicine attending physicians and senior fellows at each site were first oriented to a checklist prototype, including content previously identified using a modified Delphi approach. Each site used the checklist in 2 simulated cases: an "easy airway" and a "difficult airway" scenario. Facilitators recorded verbalization, completion, and timing of checklist items. After each simulation, participants completed an anonymous usability survey. Structured debriefings were used to gather additional feedback on checklist usability. Comments from the surveys and debriefing were qualitatively analyzed using a framework approach. Responses informed human factors-based optimization of the checklist. RESULTS: Fifty-five pediatric emergency medicine physicians/fellows (4-13 per site) participated. Participants found the prototype checklist to be helpful, easy to use, clear, and of appropriate length. During the simulations, 93% of checklist items were verbalized and more than 80% were completed. Median time to checklist completion was 6.2 minutes (interquartile range, 4.8-7.1) for the first scenario and 4.2 minutes (interquartile range, 2.7-5.8) for the second. Survey and debriefing data identified the following strengths: facilitating a shared mental model, cognitively offloading the team leader, and prompting contingency planning. Suggestions for checklist improvement included clarifying specific items, providing more detailed prompts, and allowing institution-specific customization. Integration of these data with human factors heuristic inspection resulted in a final checklist. CONCLUSIONS: Simulation-based, human factors usability testing of the National Emergency Airway Registry for Pediatric Emergency Medicine Preintubation Checklist allowed optimization prior to clinical implementation. Next steps involve integration into real-world settings utilizing rigorous implementation science strategies, with concurrent evaluation of the impact on patient outcomes and safety.

Childbearing and Family Leave Policies for Physicians at US Children's Hospitals.

The objective of this study was to examine the childbirth and parental leave policies for physicians at children's hospitals. We obtained institutional policies from 15 hospitals in 2021. The median duration of full salaried leave was 8 weeks (range, 2-12 weeks). Leave policies vary widely among US children's hospitals.

Video-Assisted Laryngoscopy for Pediatric Tracheal Intubation in the Emergency Department: A Multicenter Study of Clinical Outcomes.

STUDY OBJECTIVE: To explore the association between video-assisted laryngoscopy (use of a videolaryngoscope regardless of where laryngoscopists direct their gaze), first-attempt success, and adverse airway outcomes. METHODS: We conducted an observational study using data from 2 airway consortiums that perform prospective surveillance: the National Emergency Airway Registry for Children (NEAR4KIDS) and a pediatric emergency medicine airway education collaborative. Data collected included patient and procedural characteristics and procedural outcomes. We performed multivariable analyses of the association of video-assisted laryngoscopy with individual patient outcomes and evaluated the association between site-level video-assisted laryngoscopy use and tracheal intubation outcomes. RESULTS: The study cohort included 1,412 tracheal intubation encounters performed from January 2017 to March 2021 across 11 participating sites. Overall, the first-attempt success was 70.0%. Video-assisted laryngoscopy was associated with increased odds of first-attempt success (odds ratio [OR] 2.01; 95% confidence interval [CI], 1.48 to 2.73) and decreased odds of severe adverse airway outcomes (OR 0.70; 95% CI, 0.58 to 0.85) including decreased severe hypoxia (OR 0.69; 95% CI, 0.55 to 0.87). Sites varied substantially in the use of video-assisted laryngoscopy (range from 12.9% to 97.8%), and sites with high use of video-assisted laryngoscopy (> 80%) experienced increased first-attempt success even after adjusting for individual patient laryngoscope use (OR 2.30; 95% CI, 1.79 to 2.95). CONCLUSION: Video-assisted laryngoscopy is associated with increased first-attempt success and fewer adverse airway outcomes for patients intubated in the pediatric emergency department. There is wide variability in the use of video-assisted laryngoscopy, and the high use is associated with increased odds of first-attempt success.

Development of a paediatric airway management checklist for the emergency department: a modified Delphi approach.

BACKGROUND: Airway management checklists have improved paediatric patient safety in some clinical settings, but consensus on the appropriate components to include on a checklist for paediatric tracheal intubation in the ED is lacking. METHODS: A multidisciplinary panel of 14 experts in airway management within and outside of paediatric emergency medicine participated in a modified Delphi approach to develop consensus on the appropriate components for a paediatric airway management checklist for the ED. Panel members reviewed, modified and added to the components from the National Emergency Airway Registry for Children airway safety checklist for paediatric intensive care units using a 9-point appropriateness scale. Components with a median score of 7.0-9.0 and a 25th percentile score ≥7.0 achieved consensus for inclusion. A priori, the modified Delphi method was limited to a maximum of two rounds for consensus on essential components and one additional round for checklist creation. RESULTS: All experts participated in both rounds. Consensus was achieved on 22 components. Twelve were original candidate items and 10 were newly suggested or modified items. Consensus components included the following categories: patient assessment and plan (5 items), patient preparation (5 items), pharmacy (2 items), equipment (7 items) and personnel (3 items). The components were formatted into a 17-item clinically usable checklist. CONCLUSIONS: Using the modified Delphi method, consensus was established among airway management experts around essential components for an airway management checklist intended for paediatric tracheal intubation in the ED.

Management of the Difficult Airway.

ABSTRACT: Airway management is a fundamental component of care during resuscitation of critically ill and injured children. In addition to predicted anatomic and physiologic differences in children compared with adults, certain conditions can predict potential difficulty during pediatric airway management. This review presents approaches to identifying pediatric patients in whom airway management is more likely to be difficult, and discusses strategies to address such challenges. These strategies include optimization of effective bag-mask ventilation, alternative approaches to laryngoscopy, use of adjunct airway devices, modifications to rapid sequence intubation, and performance of surgical airways in children. The importance of considering systems of care in preparing for potentially difficult pediatric airways is also discussed.

Association between the number of endotracheal intubation attempts and rates of adverse events in a paediatric emergency department.

BACKGROUND: Challenges in emergent airway management in children can affect intubation success. It is unknown if number of endotracheal intubation attempts is associated with rates of adverse events in the paediatric ED setting. OBJECTIVE: We sought to (1) Identify rates of intubation-related adverse events, (2) Evaluate the association between the number of intubation attempts and adverse events in a paediatric ED, and (3) Determine the effect of videolaryngoscopy on these associations. DESIGN AND METHODS: We performed a retrospective observational study of patients who underwent endotracheal intubation in a paediatric ED in the USA between January 2004 and December 2018. Data on patient-related, provider-related and procedure-related characteristics were obtained from a quality assurance database and the health record. Our primary outcome was frequency of intubation-related adverse events, categorised as major and minor. The number of intubation attempts was trichotomised to 1, 2, and 3 or greater. Multivariable logistic regression models were used to determine the relationship between the number of intubation attempts and odds of adverse events, adjusting for demographic and clinical factors. RESULTS: During the study period, 628 patients were intubated in the ED. The overall rate of adverse events was 39%. Hypoxia (19%) was the most common major event and mainstem intubation (15%) the most common minor event. 72% patients were successfully intubated on the first attempt. With two intubation attempts, the adjusted odds of any adverse event were 3.26 (95% CI 2.11 to 5.03) and with ≥3 attempts the odds were 4.59 (95% CI 2.23 to 9.46). Odds similarly increased in analyses of both major and minor adverse events. This association was consistent for both traditional and videolaryngoscopy. CONCLUSION: Increasing number of endotracheal intubation attempts was associated with higher odds of adverse events. Efforts to optimise first attempt success in children undergoing intubation may mitigate this risk and improve clinical outcomes.

Hydrolytically Stable Ionic Fluorogels for High-Performance Remediation of Per- and Polyfluoroalkyl Substances (PFAS) from Natural Water.

PFAS are known bioaccumulative and persistent chemicals which pollute natural waters globally. There exists a lack of granular sorbents to efficiently remove both legacy and emerging PFAS at environmentally relevant concentrations. Herein, we report a class of polymer networks with a synergistic combination of ionic and fluorous components that serve as granular materials for the removal of anionic PFAS from water. A library of Ionic Fluorogels (IFs) with systematic variation in charge density and polymer network architecture was synthesized from hydrolytically stable fluorous building blocks. The IFs were demonstrated as effective sorbents for the removal of 21 legacy and emerging PFAS from a natural water and were regenerable over multiple cycles of reuse. Comparison of one IF to a commercial ion exchange resin in mini-rapid small-scale column tests demonstrated superior performance for the removal of short-chain PFAS from natural water under operationally relevant conditions.

Artificial Metalloproteins with Dinuclear Iron-Hydroxido Centers.

Dinuclear iron centers with a bridging hydroxido or oxido ligand form active sites within a variety of metalloproteins. A key feature of these sites is the ability of the protein to control the structures around the Fe centers, which leads to entatic states that are essential for function. To simulate this controlled environment, artificial proteins have been engineered using biotin-streptavidin (Sav) technology in which Fe complexes from adjacent subunits can assemble to form [FeIII-(µ-OH)-FeIII] cores. The assembly process is promoted by the site-specific localization of the Fe complexes within a subunit through the designed mutation of a tyrosinate side chain to coordinate the Fe centers. An important outcome is that the Sav host can regulate the Fe···Fe separation, which is known to be important for function in natural metalloproteins. Spectroscopic and structural studies from X-ray diffraction methods revealed uncommonly long Fe···Fe separations that change by less than 0.3 Å upon the binding of additional bridging ligands. The structural constraints imposed by the protein host on the di-Fe cores are unique and create examples of active sites having entatic states within engineered artificial metalloproteins.

Nontargeted Analysis Study Reporting Tool: A Framework to Improve Research Transparency and Reproducibility.

Non-targeted analysis (NTA) workflows using mass spectrometry are gaining popularity in many disciplines, but universally accepted reporting standards are nonexistent. Current guidance addresses limited elements of NTA reporting-most notably, identification confidence-and is insufficient to ensure scientific transparency and reproducibility given the complexity of these methods. This lack of reporting standards hinders researchers' development of thorough study protocols and reviewers' ability to efficiently assess grant and manuscript submissions. To overcome these challenges, we developed the NTA Study Reporting Tool (SRT), an easy-to-use, interdisciplinary framework for comprehensive NTA methods and results reporting. Eleven NTA practitioners reviewed eight published articles covering environmental, food, and health-based exposomic applications with the SRT. Overall, our analysis demonstrated that the SRT provides a valid structure to guide study design and manuscript writing, as well as to evaluate NTA reporting quality. Scores self-assigned by authors fell within the range of peer-reviewer scores, indicating that SRT use for self-evaluation will strengthen reporting practices. The results also highlighted NTA reporting areas that need immediate improvement, such as analytical sequence and quality assurance/quality control information. Although scores intentionally do not correspond to data/results quality, widespread implementation of the SRT could improve study design and standardize reporting practices, ultimately leading to broader use and acceptance of NTA data.

The Impact of Videolaryngoscopy on Endotracheal Intubation Success by a Pediatric/Neonatal Critical Care Transport Team.

INTRODUCTION: Endotracheal intubation may be required for the transport of critically ill neonates and children. Data suggest that first pass success (FPS) is associated with lower rates of complications. Thus, understanding factors associated with FPS can have important implications for clinical outcomes. We aimed to determine the impact of videolaryngoscopy (VL) on FPS by a pediatric critical care transport team (CCTT). Methods: We performed a retrospective cross-sectional study on pediatric patients (≤ 18 years of age) requiring endotracheal intubation by a tertiary care-based pediatric CCTT between 2011 and 2019. Patients were categorized as neonatal (≤ 28 days of age, either preterm or term) or pediatric (> 28 days of age). All intubation attempts using VL were performed with the C-MAC videolaryngoscope. Our primary outcome was rate of FPS. Descriptive statistics of patient, provider, and procedure characteristics were calculated. Multivariate regression was used to test the association between FPS and type of laryngoscope (video versus direct) adjusting for significant clinical predictors. Results: Over the study period, 135 patients were intubated by the CCTT. Sixty percent of these patients were neonates, and 40% were pediatric. The overall FPS rate was 61%, with lower rates in neonates (54%) and higher rates in pediatric patients (70%). Use of videolaryngoscopy increased over the study period. First pass success rate using the C-MAC videolaryngoscope was 72% compared to 42% for direct laryngoscopy across the whole study population. In adjusted analyses, FPS using VL was significantly higher in the pediatric patient population (aOR 12.42 [95%CI 3.33, 46.29]), but not in neonates (aOR 1.08 [0.44, 2.63]). Use of VL increased significantly over the study period. Conclusion: We found use of a C-MAC videolaryngoscope by a critical care transport team was associated with improved FPS during endotracheal intubation of pediatric patients but not neonates, after controlling for other patient and provider characteristics. In addition to the impact on FPS, use of VL may offer additional educational and quality benefits.

Deep stool microbiome analysis in cirrhosis reveals an association between short-chain fatty acids and hepatic encephalopathy.

INTRODUCTION AND OBJECTIVES: Hepatic encephalopathy (HE) is a complication of cirrhosis linked to the microbiome. We aimed to characterize the fecal microbiome of patients with prior and future overt HE, and explore the relationship between fecal species, short-chain fatty acids (SCFAs) and ammonia on HE pathogenesis. MATERIALS AND METHODS: Consecutive inpatients and outpatients with cirrhosis were recruited. A single stool sample was collected and underwent shallow shotgun sequencing, and SCFA and ammonia quantification. Patients were followed until the end of the study period. Prior and new overt HE was diagnosed by the treating hepatologist. RESULTS: Forty-nine patients with cirrhosis, mean MELD-Na 20 (SD = 9) and 33 (67%) with a history of OHE provided a stool sample. Over a median 85 days of follow up (interquartile range 34-181 days), 16 developed an OHE episode. Eight fecal bacterial species were associated with a history of OHE, and no species predicted future OHE. Bacterial species positively associated with SCFA content were inversely related to cirrhosis disease severity. Patients with a history of OHE had lower concentrations of 6 fecal SCFAs. Fecal ammonia concentrations were similar between those with and without a history of OHE (273 µmol/g ± 214 vs. 327 ±â€¯234, P = 0.43). CONCLUSIONS: We found 8 fecal species and 6 SCFAs linked to OHE. Many of the species inversely linked to OHE also have an association with SCFA production. Further work is needed to detail this relationship and to develop targeted interventions to treat HE.

Technical factors associated with first-pass success during endotracheal intubation in children: analysis of videolaryngoscopy recordings.

BACKGROUND: First-pass success (FPS) during intubation is associated with lower morbidity for paediatric patients. Using videolaryngoscopy (VL) recordings, we reviewed technical aspects of intubation, including factors associated with FPS in children. METHODS: We performed a retrospective study of intubation attempts performed using video-assisted laryngoscopy in a paediatric ED between January 2014 and December 2018. Data were abstracted from a quality assurance database, the electronic medical record and VL recordings. Our primary outcome was FPS. Intubation practices were analysed using descriptive statistics. Patient and procedural characteristics associated with FPS in univariate testing and clinical factors identified from the literature were included as covariates in a multivariable logistic regression. An exploratory analysis examined the relationship between position of the glottic opening on the video screen and FPS. RESULTS: Intubation was performed during 237 patient encounters, with 231 using video-assisted laryngoscopy. Data from complete video recordings were available for 129 attempts (59%); an additional 31 (13%) had partial recordings. Overall, 173 (73%) of first attempts were successful. Adjusting for patient age, placing the blade tip into the vallecula adjusted OR ((aOR) 7.2 (95% CI 1.7 to 30.1)) and obtaining a grade 1 or 2a-modified Cormack-Lehane glottic view on the videolaryngoscope screen (aOR 6.1 (95% CI 1.5 to 25.7) relative to grade 2b) were associated with increased FPS in the subset of patients with complete recordings. Exploratory analysis suggested that FPS is highest (81%) and duration is shortest when the glottic opening is located in the second quintile of the video screen. CONCLUSIONS: Placement of the blade tip into the vallecula regardless of blade type, sufficient glottic visualisation and locating the glottic opening within the second quintile of the video screen were associated with FPS using video-assisted laryngoscopy in the paediatric ED.

Use of the C-MAC Macintosh 0 Blade for Intubation of Infants in the Emergency Department.

ABSTRACT: First-pass success rates during intubation of infants in the emergency department have been shown to be low. Video laryngoscopy is being increasingly used during advanced airway management in the emergency department, but available data have not supported improved outcomes with use in pediatrics. The newly available Macintosh size 0 (curved) blade for the C-MAC video laryngoscope offers a narrower blade for use in infants. We describe the use of the new C-MAC Macintosh 0 blade for intubation of 2 infants with apnea secondary to respiratory syncytial virus bronchiolitis. The included video recording demonstrates the favorable glottic view and improved maneuverability offered by the narrower blade but also highlights the limitation in use beyond young infants given the short blade length.

Artificial Iron Proteins: Modeling the Active Sites in Non-Heme Dioxygenases.

An important class of non-heme dioxygenases contains a conserved Fe binding site that consists of a 2-His-1-carboxylate facial triad. Results from structural biology show that, in the resting state, these proteins are six-coordinate with aqua ligands occupying the remaining three coordination sites. We have utilized biotin-streptavidin (Sav) technology to design new artificial Fe proteins (ArMs) that have many of the same structural features found within active sites of these non-heme dioxygenases. An Sav variant was isolated that contains the S112E mutation, which installed a carboxylate side chain in the appropriate position to bind to a synthetic FeII complex confined within Sav. Structural studies using X-ray diffraction (XRD) methods revealed a facial triad binding site that is composed of two N donors from the biotinylated ligand and the monodentate coordination of the carboxylate from S112E. Two aqua ligands complete the primary coordination sphere of the FeII center with both involved in hydrogen bond networks within Sav. The corresponding FeIII protein was also prepared and structurally characterized to show a six-coordinate complex with two exogenous acetato ligands. The FeIII protein was further shown to bind an exogenous azido ligand through replacement of one acetato ligand. Spectroscopic studies of the ArMs in solution support the results found by XRD.

Comparison of microcapillary column length and inner diameter investigated with gradient analysis of lipids by ultrahigh-pressure liquid chromatography-mass spectrometry.

Biological samples in lipidomic studies can consist of extremely complex mixtures due to the diverse range of species and isomerism. Herein, highly efficient, in-house packed microcapillary columns introduce the potential to better separate these complex mixtures. We compared the effects of changing column length (15, 30, and 60 cm) and inner diameter (75 and 100 µm) on lipid separation efficiency by reversed-phase gradient analysis using ultrahigh-pressure liquid chromatography coupled to mass spectrometry with operating pressures ranging from 450 to 2200 bar. Seven lipid standards composed of phosphatidylcholine and triacylglycerol species were analyzed at four different gradient rates to calculate conditional peak capacity. The longest column, 60 cm, at the shallowest gradient of 2% gave the highest peak capacity of 359 with a separation window of 2 h. The intermediate column length of 30 cm with 75 µm inner diameter provided a peak capacity of 287 with a separation window of 1 h. There was no significant difference in peak capacity between 75 and 100 µm inner diameter columns. This study showed that using highly efficient microcapillary columns increased peak capacity and resolution of lipids, and thus, this technique seems promising for enhancing lipid coverage and enabling better discovery of lipid biomarkers.

Light Modulates the Physiology of Nonphototrophic Actinobacteria.

Light is a source of energy and an environmental cue that is available in excess in most surface environments. In prokaryotic systems, conversion of light to energy by photoautotrophs and photoheterotrophs is well understood, but the conversion of light to information and the cellular response to that information have been characterized in only a few species. Our goal was to explore the response of freshwater Actinobacteria, which are ubiquitous in illuminated aquatic environments, to light. We found that Actinobacteria without functional photosystems grow faster in the light, likely because sugar transport and metabolism are upregulated in the light. Based on the action spectrum of the growth effect and comparisons of the genomes of three Actinobacteria with this growth rate phenotype, we propose that the photosensor in these strains is a putative CryB-type cryptochrome. The ability to sense light and upregulate carbohydrate transport during the day could allow these cells to coordinate their time of maximum organic carbon uptake with the time of maximum organic carbon release by primary producers.IMPORTANCE Sunlight provides information about both place and time. In sunlit aquatic environments, primary producers release organic carbon and nitrogen along with other growth factors during the day. The ability of Actinobacteria to coordinate organic carbon uptake and utilization with production of photosynthate enables them to grow more efficiently in the daytime, and it potentially gives them a competitive advantage over heterotrophs that constitutively produce carbohydrate transporters, which is energetically costly, or produce transporters only after detection of the substrate(s), which delays their response. Understanding how light cues the transport of organic carbon and its conversion to biomass is key to understanding biochemical mechanisms within the carbon cycle, the fluxes through it, and the variety of mechanisms by which light enhances growth.

Clinical Practice Guideline for Emergency Department Procedural Sedation With Propofol: 2018 Update.

We update an evidence-based clinical practice guideline for the administration of propofol for emergency department procedural sedation. Both the unique considerations of using this drug in the pediatric population and the substantial new research warrant revision of the 2007 advisory. We discuss the indications, contraindications, personnel requirements, monitoring, dosing, coadministered medications, and adverse events for propofol sedation.

Distribution and Diversity of Rhodopsin-Producing Microbes in the Chesapeake Bay.

Although sunlight is an abundant source of energy in surface environments, less than 0.5% of the available photons are captured by (bacterio)chlorophyll-dependent photosynthesis in plants and bacteria. Metagenomic data indicate that 30 to 60% of the bacterial genomes in some environments encode rhodopsins, retinal-based photosystems found in heterotrophs, suggesting that sunlight may provide energy for more life than previously suspected. However, quantitative data on the number of cells that produce rhodopsins in environmental systems are limited. Here, we use total internal reflection fluorescence microscopy to show that the number of free-living microbes that produce rhodopsins increases along the salinity gradient in the Chesapeake Bay. We correlate this functional data with environmental data to show that rhodopsin abundance is positively correlated with salinity and with indicators of active heterotrophy during the day. Metagenomic and metatranscriptomic data suggest that the microbial rhodopsins in the low-salinity samples are primarily found in Actinobacteria and Bacteroidetes, while those in the high-salinity samples are associated with SAR-11 type AlphaproteobacteriaIMPORTANCE Microbial rhodopsins are common light-activated ion pumps in heterotrophs, and previous work has proposed that heterotrophic microbes use them to conserve energy when organic carbon is limiting. If this hypothesis is correct, rhodopsin-producing cells should be most abundant where nutrients are most limited. Our results indicate that in the Chesapeake Bay, rhodopsin gene abundance is correlated with salinity, and functional rhodopsin production is correlated with nitrate, bacterial production, and chlorophyll a We propose that in this environment, where carbon and nitrogen are likely not limiting, heterotrophs do not need to use rhodopsins to supplement ATP synthesis. Rather, the light-generated proton motive force in nutrient-rich environments could be used to power energy-dependent membrane-associated processes, such as active transport of organic carbon and cofactors, enabling these organisms to more efficiently utilize exudates from primary producers.

Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure.

BACKGROUND: Adolescent intermittent ethanol (AIE) exposure produces persistent impairments in cholinergic and epigenetic signaling and alters markers of synapses in the hippocampal formation, effects that are thought to drive hippocampal dysfunction in adult rodents. Donepezil (Aricept), a cholinesterase inhibitor, is used clinically to ameliorate memory-related cognitive deficits. Given that donepezil also prevents morphological impairment in preclinical models of neuropsychiatric disorders, we investigated the ability of donepezil to reverse morphological and epigenetic adaptations in the hippocampus of adult rats exposed to AIE. Because of the known relationship between dendritic spine density and morphology with the fragile X mental retardation 1 (Fmr1) gene, we also assessed Fmr1 expression and its epigenetic regulation in hippocampus after AIE and donepezil pretreatment. METHODS: Adolescent rats were administered intermittent ethanol for 16 days starting on postnatal day 30. Rats were treated with donepezil (2.5 mg/kg) once a day for 4 days starting 20 days after the completion of AIE exposure. Brains were dissected out after the fourth donepezil dose, and spine analysis was completed in dentate gyrus granule neurons. A separate cohort of rats, treated identically, was used for molecular studies. RESULTS: AIE exposure significantly reduced dendritic spine density and altered morphological characteristics of subclasses of dendritic spines. AIE exposure also increased mRNA levels and H3-K27 acetylation occupancy of the Fmr1 gene in hippocampus. Treatment of AIE-exposed adult rats with donepezil reversed both the dendritic spine adaptations and epigenetic modifications and expression of Fmr1. CONCLUSIONS: These findings indicate that AIE produces long-lasting decreases in dendritic spine density and changes in Fmr1 gene expression in the hippocampal formation, suggesting morphological and epigenetic mechanisms underlying previously reported behavioral deficits after AIE. The reversal of these effects by subchronic, post-AIE donepezil treatment indicates that these AIE effects can be reversed by up-regulating cholinergic function.