Upcycling Romaine lettuce outer leaves by infrared blanching and hot air drying.

Romaine lettuce outer leaves, as opposed to the more commonly marketed heart, are typically discarded and present an opportunity for upcycling as dried powders. Duquesne Romaine lettuce was evaluated to quantify and compare quality attributes of fresh outer and heart leaves, dried powders following hot air drying, and dried powders following an infrared (IR) blanching pretreatment before drying. Attributes measured for fresh leaves included moisture, water activity (Aw), color, total soluble phenolics (TSP), and antioxidant capacity (AC). Drying kinetics and time/energy saving through IR blanching were evaluated. Attributes measured for dried powders included moisture, Aw, color, true density, water vapor isotherms, TSP, AC, cadmium (Cd) content, and pesticide residues. TSP, AC, Cd, and pesticide residues were higher, whereas moisture content and Aw were lower in fresh outer versus heart leaves. Hot air drying reduced TSP and AC to 63.6% and 35.2% of fresh values, respectively, whereas IR blanching further reduced TSP and AC to 37.3% and 25.4% in outer leave powders. On the other hand, TSP and AC increased 237% and 151%, respectively, for unblanched heart powders. Higher increase of TSP than AC in heart leaf powder may indicate synthesis of phenolic compounds activated by abiotic stresses such as cutting and high temperatures at the initial drying stage. IR blanching resulted in significant time/energy savings for drying of outer leaves. Microbial loads were substantially reduced during drying, although microbial population on outer leaves were more resistant. Safe to eat outer leaf Romaine lettuce powders can be produced, assuming appropriate agricultural practices.

Correction: Randomized nutrient bar supplementation improves exercise-associated changes in plasma metabolome in adolescents and adult family members at cardiometabolic risk.

[This corrects the article DOI: 10.1371/journal.pone.0240437.].

Quality assessment of polymer materials for human model eye development.

PURPOSE: We developed model eyes using six polymer materials to determine which materials were most appropriate in simulating real human sclera and extraocular muscle (EOM). METHODS: Five three-dimensional (3-D) printed polymers (FlexFill, PolyFlex, PCTPE, Soft PLA, and NinjaFlex) and one silicone material were systematically tested by board-certified ophthalmologists and senior ophthalmology residents. Material testing included scleral passes with 6-0 Vicryl sutures through each eye model. Participants completed a survey designed to collect demographic data, subjective assessment of each material's accuracy in simulating real human sclera and EOM, and a ranking for each polymer material to identify which would be most suitable for an ophthalmic surgery training tool. The Wilcoxon signed-rank test was conducted to determine if there was a statistically significant difference in the distribution of ranks between the polymer materials. RESULTS: The distribution of ranks for silicone material's "sclera" and "EOM" components were statistically significantly higher than that of all other polymer materials (all p < 0.05). Silicone material received the highest rank for both "sclera" and "EOM" components. Survey results indicated that the silicone material effectively simulated real human tissue. CONCLUSION: Silicone model eyes performed better than 3-D printed polymers as an educational tool for incorporation into a microsurgical training curriculum. Silicone models provide a low-cost teaching tool that allows for independent practice of microsurgical techniques without requiring a wet-laboratory facility.

Sealing ability in vitro study and biocompatibility in vivo animal study of different bioceramic based sealers.

INTRODUCTION: The effectiveness of root canal therapy in endodontic practice is largely determined by providing a compact fluid-tight closure at the apex of the root canal, which inhibits irritant entry and buildup, which leads to a biological breakdown of the attachment mechanism and failure. During obturation, along with gutta-percha, root canal sealers are employed to fill voids and seal root canals. Root canal sealers come in a variety of shapes and sizes, each with its own set. AIM: Evaluation of sealing ability in vitro study by using scanning electron microscopy (SEM) and biocompatibility in vivo animals study of BioRoot RCS and meta Biomed bio_ceramic sealer (CeraSeal RCS) and compared the findings with that of Zinc oxide eugenol (ZOE) sealer as control. MATERIALS AND METHODS: This study utilized two bio_ceramic sealers (BioRoot RCS and meta Biomed bio_ceramic sealer (CeraSeal RCS) and compared the findings with that of ZOE sealer as control. Biocompatibility was determined by examining histopathological biopsy specimens collected from rabbits. Each rabbit had four dentin tubes implanted into the subcutaneous tissues, one for BioRoot RCS, one for CeraSeal RCS, and one for ZOE RCS, with the fourth tube being empty haematoxylin and eosin were used to stain histological sections, and a light microscope was used to evaluate them. Extracted human single canal premolars were used to evaluate the sealing ability. The root canals were divided into three sections (coronal, middle, and apical). SEM was used to assess the adhesion quality at the sealer-dentin interface. RESULTS: BioRoot and CeraSeal sealers have excellent sealing adaptation and biocompatibility, as well as rapid tissue recovery, while ZOE sealers have a slower recovery of inflammatory reaction results when compared to bio_root and ceraSeal sealers, as well as a less sealing adaptation than the two other bio_ceramic sealers. CONCLUSION: In general, the two bioceramic sealers tested were biocompatible and capable of sealing or adhesion. While ZOE had less adherence ability and less biocompatibility.

Splicing is an alternate oncogenic pathway activation mechanism in glioma.

High-grade diffuse glioma (HGG) is the leading cause of brain tumour death. While the genetic drivers of HGG have been well described, targeting these has thus far had little impact on survival suggesting other mechanisms are at play. Here we interrogate the alternative splicing landscape of pediatric and adult HGG through multi-omic analyses, uncovering an increased splicing burden compared with normal brain. The rate of recurrent alternative splicing in cancer drivers exceeds their mutation rate, a pattern that is recapitulated in pan-cancer analyses, and is associated with worse prognosis in HGG. We investigate potential oncogenicity by interrogating cancer pathways affected by alternative splicing in HGG; spliced cancer drivers include members of the RAS/MAPK pathway. RAS suppressor neurofibromin 1 is differentially spliced to a less active isoform in >80% of HGG downstream from REST upregulation, activating the RAS/MAPK pathway and reducing glioblastoma patient survival. Overall, our results identify non-mutagenic mechanisms by which cancers activate oncogenic pathways which need to accounted for in personalized medicine approaches.

Health benefits of first and second extraction drum-dried pitted olive pomace.

Olive pomace (OP) is the main by-product of olive oil extraction. After pit and skin removal, OP pulp has high concentrations of dietary fiber and phenolics with high antioxidant capacity. This study evaluated mice health benefits of drum-dried pitted OP pulp obtained after first and second oil extraction. Fresh OP was steam blanched, then pits and skins separated in a pulper/finisher, and pulp drum-dried and milled. OP was characterized by proximate analysis, total soluble phenolics (TSP), individual phenolics, and dietary fiber. Drum-dried pitted OP from first and second extraction was formulated at 10% and 20% in a high fat mice diet. Low fat (5%) and high fat (18%) control diets were also used for comparison. First extraction OP had higher TSP than OP from second extraction. Hydroxytyrosol was the main phenolic in OP. Mice weight gain was lower for the four OP diets compared to high and low-fat control diets. Fecal protein was high for all OP diets, indicating poor protein retention in mice, possibly by phenolics binding of protein and enzymes. Liver weight and adipose tissue were lower in mice consuming the four high fat OP diets compared to high fat control diet. Also, there was no effect on blood glucose by OP in diets. Mice gut microbiota analysis indicated that Actinobacteria decreased in the OP diets compared to the two control diets while Bacteroidetes increased, indicating a positive correlation with reduced body fat and weight. Drum-dried pitted OP is a novel agricultural by-product with its bioactive compounds having the potential to be incorporated in feeds and foods providing health benefits. PRACTICAL APPLICATION: Drum-dried pitted olive pomace can be produced from first or second olive oil extraction byproducts to be used as a shelf-stable healthy food or feed supplement.

Quality of Life after Laparoscopic and Open Abdominal Myomectomy.

STUDY OBJECTIVE: To evaluate the baseline and postoperative changes in quality of life and symptom-severity scores in women undergoing laparoscopic or open abdominal myomectomy for symptomatic myomas. DESIGN: Prospective cohort study of patients choosing myomectomy for symptomatic uterine myomas. SETTING: Academic medical center. PATIENTS: A total of 143 women enrolled in the study. Of these, 80 women completed both a preoperative questionnaire and at least 1 postoperative questionnaire between 6 and 27 months after surgery. INTERVENTIONS: A total of 52 women had open abdominal myomectomy, and 28 had laparoscopic myomectomy between October 2014 and September 2017. MEASUREMENTS AND MAIN RESULTS: The results of the Uterine Fibroid Symptom and Health-Related Quality-of-Life Questionnaire were compared before and after laparoscopic or open myomectomy. Women undergoing open abdominal myomectomy had larger and more numerous myomas than women undergoing laparoscopic myomectomy. Baseline quality-of-life scores were less adversely affected for women having laparoscopic myomectomy (mean [standard deviation], 57 [24] laparoscopic vs 43 [19] open abdominal, p = .01). However, baseline symptom-severity scores were statistically similar (49 [22] for laparoscopic and 57 [20] for open abdominal, p = .08) approaches. Six to 12 months after surgery, both open abdominal and laparoscopic surgeries provided excellent and similar improvements in symptom-severity and quality of life (postoperative symptoms severity scores, mean [standard deviation], 20 [14] laparoscopic vs 13 [11] open abdominal, p = .24 and quality-of-life scores, mean [standard deviation], 91 [16] laparoscopic vs 88 [17] open abdominal, p = .49). These improvements were sustained for women who returned questionnaires up to 27 months of follow-up. CONCLUSION: Women with symptomatic myomas have a compromised quality of life, and they experience a similarly dramatic improvement in quality of life and decrease in symptom-severity after both laparoscopic and open abdominal myomectomies.

Randomized nutrient bar supplementation improves exercise-associated changes in plasma metabolome in adolescents and adult family members at cardiometabolic risk.

BACKGROUND: Poor diets contribute to metabolic complications of obesity, insulin resistance and dyslipidemia. Metabolomic biomarkers may serve as early nutrition-sensitive health indicators. This family-based lifestyle change program compared metabolic outcomes in an intervention group (INT) that consumed 2 nutrient bars daily for 2-months and a control group (CONT). METHODS: Overweight, predominantly minority and female adolescent (Teen)/parent adult caretaker (PAC) family units were recruited from a pediatric obesity clinic. CONT (8 Teen, 8 PAC) and INT (10 Teen, 10 PAC) groups randomized to nutrient bar supplementation attended weekly classes that included group nutrition counseling and supervised exercise. Pre-post physical and behavioral parameters, fasting traditional biomarkers, plasma sphingolipids and amino acid metabolites were measured. RESULTS: In the full cohort, a baseline sphingolipid ceramide principal component composite score correlated with adiponectin, triglycerides, triglyceride-rich very low density lipoproteins, and atherogenic small low density lipoprotein (LDL) sublasses. Inverse associations were seen between a sphingomyelin composite score and C-reactive protein, a dihydroceramide composite score and diastolic blood pressure, and the final principal component that included glutathionone with fasting insulin and the homeostatic model of insulin resistance. In CONT, plasma ceramides, sphinganine, sphingosine and amino acid metabolites increased, presumably due to increased physical activity. Nutrient bar supplementation (INT) blunted this rise and significantly decreased ureagenic, aromatic and gluconeogenic amino acid metabolites. Metabolomic changes were positively correlated with improvements in clinical biomarkers of dyslipidemia. CONCLUSION: Nutrient bar supplementation with increased physical activity in obese Teens and PAC elicits favorable metabolomic changes that correlate with improved dyslipidemia. The trial from which the analyses reported upon herein was part of a series of nutrient bar clinical trials registered at clinicaltrials.gov as NCT02239198.

Description of a pharmacist-driven safety algorithm in Staphylococcus aureus bacteremia: Compliance, interventions, and good saves.

OBJECTIVE: To evaluate the impact of a pharmacist-driven Staphylococcus aureus bacteremia (SAB) safety bundle supported by leadership and to compare compliance before and after implementation. DESIGN: Retrospective cohort study with descriptive and before-and-after analyses. SETTING: Tertiary-care academic medical center. PATIENTS: All patients with documented SAB, regardless of the source of infection, were included. Patients transitioned to palliative care were excluded from before-and-after analysis. METHODS: A pharmacist-driven safety bundle including documented clearance of bacteremia, echocardiography, removal of central venous catheters, and targeted intravenous therapy of at least 2 weeks duration was implemented in November 2015 and was supported by leadership with stepwise escalation for nonresponse. A descriptive analysis of all patients with SAB during the study period included pharmacy interventions, acceptance rates, and escalation rates. A pre-post implementation analysis of 100 sequential patients compared bundle compliance and descriptive parameters. RESULTS: Overall, 391 interventions were made in the 20-month period following implementation, including 20 "good saves" avoiding potentially major adverse events. No statistically significant differences in complete bundle compliance were detected between the periods (74% vs 84%; P = .08). However, we detected a significant increase in echocardiography after the bundle was implemented (83% vs 94%; P = .02) and fewer patients received suboptimal definitive therapy after the bundle was implemented (10% vs 3%; P = .045). CONCLUSIONS: This pharmacist-driven SAB safety bundle with leadership support showed improvement in process measures, which may have prevented major adverse events, even with available infectious diseases (ID) consultation. It provides a critical safety net for institutions without mandatory ID consultation or with limited antimicrobial stewardship resources.

Minimum inhibitory concentration changes in relapsed left ventricular assist device driveline infections.

Driveline infection is the most common infectious complication in patients with left ventricular assist devices. Minimum inhibitory concentration changes are not well described in relapsed driveline infections. This retrospective descriptive epidemiology study of patients with left ventricular assist device implantation between January 1, 2013, and August 1, 2017, who developed driveline infection with positive cultures aimed to describe minimum inhibitory concentration changes. Of the 330 patients underwent left ventricular assist device implantation, 30 (9%) met criteria for driveline infection. Median duration of follow-up was 26 months (interquartile range 16, 39) and time to first driveline infection was 171 days (interquartile range 83, 403). There were 74 driveline infections: 40 new and 34 relapsed. Staphylococcus aureus was most common in new and relapsed driveline infection. Thirteen patients comprised the 34 relapsed infections, 9 of which experienced a minimum inhibitory concentration change. Median time to first minimum inhibitory concentration change was 56 days (interquartile range 36-88), and type of minimum inhibitory concentration change was an increase in five cases, decrease in two cases, and both increase and decrease in two cases. Minimum inhibitory concentration changes did not result in resistance in S. aureus but did in Pseudomonas aeruginosa and Mycobacterium fortuitum relapsed driveline infection. Time to first relapse from initial infection was longer in those who received suppressive therapy, 60 days versus 83 days, p = 0.047. Relapsed driveline infections were most common with S. aureus. Minimum inhibitory concentration changes were quite variable and may not be the major contributor to relapsed infection in gram-positive driveline infection.

Hypocholesterolemic Effects of Expeller-Pressed and Solvent-Extracted Fruit Seed Oils and Defatted Pomegranate Seed Meals.

Consumptions of fruit seed oils and meals could potentially improve cardiovascular health by reducing plasma total cholesterol and low-density lipoprotein (LDL). The study objective was to compare the effectiveness of expeller-pressed and solvent-extracted grape, tomato, pomegranate seed oils, and defatted pomegranate meals in lowering plasma and hepatic cholesterol using hamster models. Hamsters were fed with fruit seed oils (FSO), defatted pomegranate seed meals (PDM), or control diets. After a 3-week feeding period, plasma total triglycerides of treatment diets were significantly lower. FSO also reduced total, very-low-density lipoprotein- (VLDL), and LDL-cholesterols, while PDM only lowered VLDL-cholesterols. Decreases in low-density and high-density lipoproteins (LDL/HDL) ratios were also observed in most treatments. In liver, triglycerides, total, and free cholesterol levels did not vary between control and treatments. There were no significant differences in lipid modulating properties between solvent-extracted and expeller-pressed oils. In conclusion, partial replacements of saturated fat in high-fat diets with tomato, pomegranate, and grape seed oils could effectively reduce plasma triglyceride levels and improve HDL/LDL ratios.

Blood oxytocin concentration positively predicts contagious yawning behavior in children with autism spectrum disorder.

Research suggests that children with autism spectrum disorder (ASD) may have reduced empathy, as measured by an impaired contagious yawn response, compared to typically developing (TD) children. Other research has failed to replicate this finding, instead attributing this phenomenon to group differences in attention paid to yawn stimuli. A third possibility is that only a subgroup of children with ASD exhibits the impaired contagious yawn response, and that it can be identified biologically. Here we quantified blood concentrations of the "social" neuropeptide oxytocin (OXT) and evaluated yawning behavior and attention rates during a laboratory task in children with ASD (N = 34) and TD children (N = 30) aged 6-12 years. No group difference in contagious yawning behavior was found. However, a blood OXT concentration × group (ASD vs. TD) interaction positively predicted contagious yawning behavior (F1,50 = 7.4987; P = 0.0085). Specifically, blood OXT concentration was positively related to contagious yawning behavior in children with ASD, but not in TD children. This finding was not due to delayed perception of yawn stimuli and was observed whether attention paid to test stimuli and clinical symptom severity were included in the analysis or not. These findings suggest that only a biologically defined subset of children with ASD exhibits reduced empathy, as measured by the impaired contagious yawn response, and that prior conflicting reports of this behavioral phenomenon may be attributable, at least in part, to variable mean OXT concentrations across different ASD study cohorts. Autism Res 2019, 12: 1156-1161. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism may contagiously yawn (i.e., yawn in response to another's yawn) less often than people without autism. We find that people with autism who have lower levels of blood oxytocin (OXT), a hormone involved in social behavior and empathy, show decreased contagious yawning, but those who have higher blood OXT levels do not differ in contagious yawning from controls. This suggests that decreased contagious yawning may only occur in a biologically defined subset of people with autism.

Phenolics and Antioxidant Capacity of Pitted Olive Pomace Affected by Three Drying Technologies.

This study investigated drum-drying's ability to produce dried food-grade olive pomace as a potential food ingredient that is more nutritionally dense than its freeze-dried and hot-air dried counterparts. The pits and skin were removed from fresh olive pomace, and the remaining pulp was dried to <5% moisture through freeze-drying, hot-air drying, and drum-drying at two rotational speeds. The drying treatments had no significant (P ≤ 0.05) effect on the olive pomace's fat or dietary fiber contents but did increase the L* , a* , and b* color parameter values. Although all the drying treatments significantly (P ≤ 0.05) decreased the fresh olive pomace's antioxidant capacity, drum-drying preserved the olive pomace's antioxidant capacity significantly (P ≤ 0.05) better than freeze-drying and hot-air drying. The drum-dried samples had concentrations of caffeic acid and verbascoside that were significantly (P ≤ 0.05) higher than the other dried pomace samples and were not significantly (P ≤ 0.05) different from the fresh pomace. The drum-dried olive pomace contained concentrations of hydroxytyrosol, tyrosol, vanillic acid, luteolin-7-glucoside, and rutin that were not significantly (P ≤ 0.05) different from the dried sample with the highest concentration of each respective phenolic compound. No oleuropein was found in the fresh or dried olive pomace. The results of this study show that drum-drying is an energy efficient method for converting olive pomace into a stable food-grade supplement that preserves its high phenolic, antioxidant, and dietary fiber contents to potentially benefit human health when incorporated into food or supplement products. PRACTICAL APPLICATION: Pitting and drying converts the olive pomace into a stable form that is free of physical hazards and could be incorporated into food products to increase their nutritional quality through olive pomaces' high fiber, antioxidant, and phenolic contents. Drum-drying allows food-grade olive pomace to retain higher amounts of beneficial soluble phenolics and a higher antioxidant capacity than conventional drying methods, thus furthering olive pomace's potential valorization as a food ingredient.

Transcriptional repressor REST drives lineage stage-specific chromatin compaction at Ptch1 and increases AKT activation in a mouse model of medulloblastoma.

In medulloblastomas (MBs), the expression and activity of RE1-silencing transcription factor (REST) is increased in tumors driven by the sonic hedgehog (SHH) pathway, specifically the SHH-α (children 3 to 16 years) and SHH-ß (infants) subgroups. Neuronal maturation is greater in SHH-ß than SHH-α tumors, but both correlate with poor overall patient survival. We studied the contribution of REST to MB using a transgenic mouse model (RESTTG ) wherein conditional NeuroD2-controlled REST transgene expression in lineage-committed Ptch1 +/- cerebellar granule neuron progenitors (CGNPs) accelerated tumorigenesis and increased penetrance and infiltrative disease. This model revealed a neuronal maturation context-specific antagonistic interplay between the transcriptional repressor REST and the activator GLI1 at Ptch1 Expression of Arrb1, which encodes ß-arrestin1 (a GLI1 inhibitor), was substantially reduced in proliferating and, to a lesser extent, lineage-committed RESTTG cells compared with wild-type proliferating CGNPs. Lineage-committed RESTTG cells also had decreased GLI1 activity and increased histone H3K9 methylation at the Ptch1 locus, which correlated with premature silencing of Ptch1 These cells also had decreased expression of Pten, which encodes a negative regulator of the kinase AKT. Expression of PTCH1 and GLI1 were less, and ARRB1 was somewhat greater, in patient SHH-ß than SHH-α MBs, whereas that of PTEN was similarly lower in both subtypes than in others. Inhibition of histone modifiers or AKT reduced proliferation and induced apoptosis, respectively, in cultured REST-high MB cells. Our findings linking REST to differentiation-specific chromatin remodeling, PTCH1 silencing, and AKT activation in MB tissues reveal potential subgroup-specific therapeutic targets for MB patients.

Deficient auditory predictive coding during vocalization in the psychosis risk syndrome and in early illness schizophrenia: the final expanded sample.

BACKGROUND: During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds. Previously, we found attenuated vocalization-related auditory cortical suppression in psychosis and a similar trend in the psychosis risk syndrome. Here, we report data from the final sample of early illness schizophrenia patients (ESZ), individuals at clinical high risk for psychosis (CHR), and healthy controls (HC). METHODS: Event-related potentials (ERP) were recorded from ESZ (n = 84), CHR (n = 71), and HC (n = 103) participants during a vocalization paradigm. The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Age effects on N1 suppression (Talk-Listen), Talk N1, and Listen N1 were compared across groups. N1 measures were adjusted for normal aging before testing for group differences. RESULTS: Both ESZ and CHR groups showed reduced Talk-Listen N1 suppression relative to HC, but did not differ from each other. Listen N1 was reduced in ESZ, but not in CHR, relative to HC. Deficient Talk-Listen N1 suppression was associated with greater unusual thought content in CHR individuals. N1 suppression increased with age in HC (12-36 years), and while CHR individuals showed a similar age-related increase, no such relationship was evident in ESZ. CONCLUSIONS: Putative efference copy/corollary discharge-mediated auditory cortical suppression during vocalization is deficient in ESZ and precedes psychosis onset, particularly in CHR individuals with greater unusual thought content. Furthermore, this suppression increases from adolescence through early adulthood, likely reflecting the effects of normal brain maturation. This maturation effect is disrupted in ESZ, presumably due to countervailing illness effects.

Preclinical Models of Pediatric Brain Tumors-Forging Ahead.

Approximately five out of 100,000 children from 0 to 19 years old are diagnosed with a brain tumor. These children are treated with medication designed for adults that are highly toxic to a developing brain. Those that survive are at high risk for a lifetime of limited physical, psychological, and cognitive abilities. Despite much effort, not one drug exists that was designed specifically for pediatric patients. Stagnant government funding and the lack of economic incentives for the pharmaceutical industry greatly limits preclinical research and the development of clinically applicable pediatric brain tumor models. As more data are collected, the recognition of disease sub-groups based on molecular heterogeneity increases the need for designing specific models suitable for predictive drug screening. To overcome these challenges, preclinical approaches will need continual enhancement. In this review, we examine the advantages and shortcomings of in vitro and in vivo preclinical pediatric brain tumor models and explore potential solutions based on past, present, and future strategies for improving their clinical relevancy.

Driving antimicrobial use improvement: attitudes of providers of adult hospital care on optimal attribution and feedback.

Understanding provider perceptions of antimicrobial use (AU) feedback is important for optimal implementation. A survey addressing AU attribution scenarios, feedback methods, and implementation barriers was distributed to inpatient providers. As AU scenarios became more complex, disagreement regarding AU attribution arose. All providers were highly concerned about barriers to AU reporting.

Psychiatry in American Medical Education: The Case of Harvard's Medical School, 1900-1945.

As American psychiatrists moved from the asylum to the private clinic during the early twentieth century, psychiatry acquired a growing presence within medical school curricula. This shift in disciplinary status took place at a time when medical education itself was experiencing a period of reform. By examining medical school registers at Harvard University, records from the Dean's office of Harvard's medical school, and oral histories, this paper examines the rise in prominence of psychiatry in medical education. Three builders of Harvard psychiatry - Elmer E. Southard, C. Macfie Campbell, and Harry C. Solomon - simultaneously sought to mark territory for psychiatry and its relevance. In doing so, they capitalized on three related elements: the fluidity that existed between psychiatry and neurology, the new venues whereby medical students gained training in psychiatry, and the broader role of patrons, professional associations, and certification boards, which sought to expand psychiatry's influence in the social and cultural life of twentieth-century America.