Preclinical evaluation of transaxial intraputaminal trajectory for enhanced distribution of grafted cells in Parkinson's disease.

OBJECTIVE: The objective of this study was to develop and evaluate the feasibility and safety of a novel transaxial surgical approach for the delivery of human induced pluripotent stem cell-derived dopaminergic neuroprogenitor cells (DANPCs) into the putamen nucleus using nonhuman primates and surgical techniques and tools relevant to human clinical translation. METHODS: Nine immunosuppressed, unlesioned adult cynomolgus macaques (4 females, 5 males) received intraputaminal injections of vehicle or DANPCs (0.9 × 105 to 1.1 × 105 cells/µL) under real-time intraoperative MRI guidance. The infusates were combined with 1-mM gadoteridol (for intraoperative MRI visualization) and delivered via two tracks per hemisphere (ventral and dorsal) using a transaxial approach. The total volumes of infusion were 25 µL and 50 µL for the right and left putamen, respectively (infusion rate 2.5 µL/min). Animals were evaluated with a battery of clinical and behavioral outcome measures and euthanized 7 or 30 days postsurgery; full necropsies were performed by a board-certified veterinary pathologist. Brain tissues were collected and processed for immunohistochemistry, including against the human-specific marker STEM121. RESULTS: The optimized surgical technique and tools produced successful targeting of the putamen via the transaxial approach. Intraoperative MR images confirmed on-target intraputaminal injections in all animals. All animals survived to scheduled termination without clinical evidence of neurological deficits. The first 4 animals to undergo surgery had mild brain swelling noted at the end of surgery, of which 3 had transient reduced vision; administration of mannitol therapy and reduced intravenous fluid during the surgical procedure addressed these complications. Immunostaining against STEM121 confirmed the presence of grafted cells along the injection track within the targeted putamen area of DANPC-treated animals. All adverse histological findings were limited in scope and consistent with surgical manipulation, injection procedure, and postsurgical inflammatory response to the mechanical disruption caused by the cannula insertion. CONCLUSIONS: The delivery system, injection procedure, and DANPCs were well tolerated in all animals. Prevention of mild brain swelling by mannitol dosing and reduction of intravenous fluids during surgery allowed visual effects to be avoided. The results of the study established that this novel transaxial approach can be used to correctly and safely target cell injections to the postcommissural putamen and support clinical investigation.

The Clinical Impact of Real-Time fMRI Neurofeedback on Emotion Regulation: A Systematic Review.

Emotion dysregulation has long been considered a key symptom in multiple psychiatric disorders. Difficulties in emotion regulation have been associated with neural dysregulation in fronto-limbic circuits. Real-time fMRI-based neurofeedback (rt-fMRI-NFB) has become increasingly popular as a potential treatment for emotional dysregulation in psychiatric disorders, as it is able to directly target the impaired neural circuits. However, the clinical impact of these rt-fMRI-NFB protocols in psychiatric populations is still largely unknown. Here we provide a comprehensive overview of primary studies from 2010 to 2023 that used rt-fMRI-NFB to target emotion regulation. We assessed 41 out of 4001 original studies for methodological quality and risk of bias and synthesised concerning the frequency of significant rt-fMRI-NFB-related effects on the neural and behaviour level. Successful modulation of brain activity was reported in between 25 and 50 percent of study samples, while neural effects in clinical samples were more diverse than in healthy samples. Interestingly, the frequency of rt-fMRI-NFB-related behavioural improvement was over 75 percent in clinical samples, while healthy samples showed behavioural improvements between 0 and 25 percent. Concerning clinical subsamples, rt-fMRI-NFB-related behavioural improvement was observed in up to 100 percent of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) samples. Substance use samples showed behavioural benefits ranging between 50 and 75 percent. Neural effects appeared to be less frequent than behavioural improvements: most neural outcomes ranged between 25 and 50 percent for MDD and substance use and between 0 and 25 percent for PTSD. Using multiple individualised regions of interest (ROIs) for rt-fMRI-NFB training resulted in more frequent behavioural benefits than rt-fMRI-NFB solely based on the amygdala or the prefrontal cortex. While a significant improvement in behavioural outcomes was reported in most clinical studies, the study protocols were heterogeneous, which limits the current evaluation of rt-fMRI-NFB as a putative treatment for emotional dysregulation.

Understanding molecular characteristics of extracellular vesicles derived from different types of mesenchymal stem cells for therapeutic translation.

Mesenchymal stem cells (MSCs) have been studied for decades as candidates for cellular therapy, and their secretome, including secreted extracellular vesicles (EVs), has been identified to contribute significantly to regenerative and reparative functions. Emerging evidence has suggested that MSC-EVs alone, could be used as therapeutics that emulate the biological function of MSCs. However, just as with MSCs, MSC-EVs have been shown to vary in composition, depending on the tissue source of the MSCs as well as the protocols employed in culturing the MSCs and obtaining the EVs. Therefore, the importance of careful choice of cell sources and culture environments is receiving increasing attention. Many factors contribute to the therapeutic potential of MSC-EVs, including the source tissue, isolation technique, and culturing conditions. This review illustrates the molecular landscape of EVs derived from different types of MSC cells along with culture strategies. A thorough analysis of publicly available omic datasets was performed to advance the precision understanding of MSC-EVs with unique tissue source-dependent molecular characteristics. The tissue-specific protein and miRNA-driven Reactome ontology analysis was used to reveal distinct patterns of top Reactome ontology pathways across adipose, bone marrow, and umbilical MSC-EVs. Moreover, a meta-analysis assisted by an AI technique was used to analyze the published literature, providing insights into the therapeutic translation of MSC-EVs based on their source tissues.

Mobile-CRISPRi protocol optimization for Vibrionaceae.

Mobile clustered regularly interspaced palindromic repeats interference (Mobile-CRISPRi) is an established method for bacterial gene expression knockdown. The deactivated Cas9 protein and guide RNA are isopropyl ß-D-1-thiogalactopyranoside inducible, and all components are integrated into the chromosome via Tn7 transposition. Here, we optimized methods specific for applying Mobile-CRISPRi in multiple Vibrio species.

CRF release from a unique subpopulation of accumbal neurons constrains action-outcome acquisition in reward learning.

Background: The nucleus accumbens (NAc) mediates reward learning and motivation. Despite an abundance of neuropeptides, peptidergic neurotransmission from the NAc has not been integrated into current models of reward learning. The existence of a sparse population of neurons containing corticotropin releasing factor (CRF) has been previously documented. Here we provide a comprehensive analysis of their identity and functional role in shaping reward learning. Methods: To do this, we took a multidisciplinary approach that included florescent in situ hybridization (N mice ≥ 3), tract tracing (N mice = 5), ex vivo electrophysiology (N cells ≥ 30), in vivo calcium imaging with fiber photometry (N mice ≥ 4) and use of viral strategies in transgenic lines to selectively delete CRF peptide from NAc neurons (N mice ≥ 4). Behaviors used were instrumental learning, sucrose preference and spontaneous exploration in an open field. Results: Here we show that the vast majority of NAc CRF-containing (NAc CRF ) neurons are spiny projection neurons (SPNs) comprised of dopamine D1-, D2- or D1/D2-containing SPNs that primarily project and connect to the ventral pallidum and to a lesser extent the ventral midbrain. As a population, they display mature and immature SPN firing properties. We demonstrate that NAc CRF neurons track reward outcomes during operant reward learning and that CRF release from these neurons acts to constrain initial acquisition of action-outcome learning, and at the same time facilitates flexibility in the face of changing contingencies. Conclusion: We conclude that CRF release from this sparse population of SPNs is critical for reward learning under normal conditions.

Importance of Multispecialty Coordination of Care in an Electroconvulsive Therapy Patient With Musculoskeletal, Neurological, and Vascular Injuries: A Case Report.

ABSTRACT: Electroconvulsive therapy (ECT) is considered an effective therapy for patients suffering from severe, life-threatening, intractable depression. This treatment modality delivers controlled electrical currents (typically no more than 100 J) under general anesthesia to induce seizure. Although generally considered to have a high safety profile, physiological changes induced during the ictal phase of ECT, such as elevation in blood pressure and intracranial pressure, impose additional risks to patients with concomitant cardiovascular or cerebrovascular conditions. We describe the successful use of ECT in a unique case complicated by a combination of acute vertebral artery dissection, traumatic intracerebral hemorrhage, and cervical spine injury sustained from a suicide attempt by intentional motor vehicle collision. Although ECT can be safely administered in the presence of recent vertebral artery dissection and traumatic intraparenchymal hemorrhage, an emphasis on multispecialty coordination is crucial to monitor and reduce the risk of elevated blood pressure and further cervical spine injury.

Prophylactic Antibiotic Choice and Deep Infection in Lower Extremity Endoprosthetic Reconstruction: Comparison of Cefazolin, Cefazolin-Vancomycin, and Alternative Regimens.

INTRODUCTION: Infection is a common mode of failure in lower extremity endoprostheses. The Prophylactic Antibiotic Regimens in Tumor Surgery trial reported that 5 days of cefazolin had no difference in surgical site infection compared with 24 hours of cefazolin. Our purpose was to evaluate infection rates of patients receiving perioperative cefazolin monotherapy, cefazolin-vancomycin dual therapy, or alternative antibiotic regimens. METHODS: A single-center retrospective review was conducted on patients who received lower extremity endoprostheses from 2008 to 2021 with minimum 1-year follow-up. Three prophylactic antibiotic regimen groups were compared: cefazolin monotherapy, cefazolin-vancomycin dual therapy, and alternative regimens. The primary outcome was deep infection, defined by a sinus tract, positive culture, or clinical diagnosis. Secondary outcomes were revision surgery, microorganisms isolated, and superficial wound issues. RESULTS: The overall deep infection rate was 10% (30/294) at the median final follow-up of 3.0 years (IQR 1.7 to 5.4). The deep infection rates in the cefazolin, cefazolin-vancomycin, and alternative regimen groups were 8% (6/72), 10% (18/179), and 14% (6/43), respectively (P = 0.625). Patients not receiving cefazolin had an 18% deep infection rate (6/34) and 21% revision surgery rate (7/34) compared with a 9% deep infection rate (24/260) (P = 0.13) and 12% revision surgery rate (31/260) (P = 0.17) in patients receiving cefazolin. In those not receiving cefazolin, 88% (30/34) were due to a documented penicillin allergy, only two being anaphylaxis. All six patients in the alternative regimen group who developed deep infections did not receive cefazolin secondary to nonanaphylactic penicillin allergy. CONCLUSION: The addition of perioperative vancomycin to cefazolin in lower extremity endoprosthetic reconstructions was not associated with a lower deep infection rate. Patients who did not receive cefazolin trended toward higher rates of deep infection and revision surgery, although not statistically significant. The most common reason for not receiving cefazolin was a nonanaphylactic penicillin allergy, highlighting the continued practice of foregoing cefazolin unnecessarily.

Spraying with encapsulated nitric oxide donor reduces weight loss and oxidative damage in papaya fruit.

The combination of nitric oxide (NO) donors with nanomaterials has emerged as a promising approach to reduce postharvest losses. The encapsulation of NO donors provides protection from rapid degradation and controlled release, enhancing the NO effectiveness in postharvest treatments. Moreover, the application method can also influence postharvest responses. In this study, two application methods were evaluated, spraying and immersion, using S-nitrosoglutathione (GSNO, a NO donor) in free and encapsulated forms on papaya fruit. Our hypothesis was that GSNO encapsulated in chitosan nanoparticles would outperform the free form in delaying fruit senescence. In addition, this study marks the pioneering characterization of chitosan nanoparticles containing GSNO within the framework of a postharvest investigation. Overall, our findings indicate that applying encapsulated GSNO (GSNO-NP-S) through spraying preserves the quality of papaya fruit during storage. This method not only minimizes weight loss, ethylene production, and softening, but also stimulates antioxidant responses, thereby mitigating oxidative damage. Consequently, it stands out as the promising technique for delaying papaya fruit senescence. This innovative approach holds the potential to enhance postharvest practices and advance sustainable agriculture.

Parallel evolution of integrated craniofacial traits in trophic specialist pupfishes.

Populations may adapt to similar environments via parallel or non-parallel genetic changes, but the frequency of these alternative mechanisms and underlying contributing factors are still poorly understood outside model systems. We used QTL mapping to investigate the genetic basis of highly divergent craniofacial traits between the scale-eater (Cyprinodon desquamator) and molluscivore (C. brontotheroides) pupfish adapting to two different hypersaline lake environments on San Salvador Island, Bahamas. We lab-reared F2 scale-eater x molluscivore intercrosses from two different lake populations, estimated linkage maps, scanned for significant QTL for 29 skeletal and craniofacial traits, female mate preference, and sex. We compared the location of QTL between lakes to quantify parallel and non-parallel genetic changes. We detected significant QTL for six craniofacial traits in at least one lake. However, nearly all shared QTL loci were associated with a different craniofacial trait within each lake. Therefore, our estimate of parallel evolution of craniofacial genetic architecture could range from one out of six identical trait QTL (low parallelism) to five out of six integrated trait QTL (high parallelism). We suggest that pleiotropy and trait integration can affect estimates of parallel evolution, particularly within rapid radiations. We also observed increased adaptive introgression in shared QTL regions, suggesting that gene flow contributed to parallel evolution. Overall, our results suggest that the same genomic regions may contribute to parallel adaptation across integrated suites of craniofacial traits, rather than specific traits, and highlight the need for a more expansive definition of parallel evolution.

Contribution of plasma levels of VEGF-A and angiopoietin-2 in addition to a genetic variant in KCNAB1 to predict the risk of bevacizumab-induced hypertension.

Bevacizumab-induced hypertension poses a therapeutic challenge and identifying biomarkers for hypertension can enhance therapy safety. Lower plasma levels of VEGF-A, angiopoietin-2, and rs6770663 in KCNAB1 were previously associated with increased risk of bevacizumab-induced hypertension. This study investigated whether these factors independently contribute to grade 2-3 bevacizumab-induced hypertension risk in 277 cancer patients (CALGB/Alliance 90401). Multivariable analyses assessed the independent association of each factor and hypertension. Likelihood ratio test (LRT) evaluated the explanatory significance of combining protein levels and rs6770663 in predicting hypertension. Boostrap was employed to assess the mediation effect of protein levels on the rs6770663 association with hypertension. Lower protein levels and rs6770663 were independently associated with increased hypertension risk. Adding rs6770663 to protein levels improved the prediction of hypertension (LRT p = 0.0002), with no mediation effect observed. Protein levels of VEGF-A, angiopoietin-2 and rs6770663 in KCNAB1 are independent risk factors and, when combined, may improve prediction of bevacizumab-induced hypertension. ClinicalTrials.gov Identifier: NCT00110214.

Recognition of online e-cigarette marketing and e-cigarette-related attitudes and behaviors among young adults.

INTRODUCTION: Past research examining the relationship between exposure to online e-cigarette marketing and e-cigarette-related attitudes and behaviors has relied on unaided recall measures that may suffer from self-report bias. To date, few studies have presented participants with e-cigarette marketing stimuli and assessed recognition. This study examined the associations between recognition of online e-cigarette marketing stimuli and e-cigarette-related attitudes and behaviors among young adults in California. METHODS: A non-probability representative sample of young adults (ages 18-24; N=1500) living in California completed an online survey assessing their recognition of online e-cigarette marketing stimuli, including image-based (i.e., Instagram, email) and audiovisual (i.e., YouTube, TikTok) promotions, and positive e-cigarette-related attitudes (e.g., appeal of e-cigarettes) and behaviors (e.g., e-cigarette use). Adjusted and weighted logistic regression analyses were used. RESULTS: 79.0% (n=1185) of young adults, including 78.1% (n=310/397) of participants under 21 years old, recognized online e-cigarette marketing. Participants who reported recognition of stimuli, compared with those who did not, had greater odds of reporting appeal of e-cigarettes (AOR=2.26, 95% CI=1.65-3.09) and e-cigarette purchase intentions (AOR=1.66, 95% CI=1.13-2.43) among all participants, and susceptibility to use e-cigarettes among never users (AOR=2.29, 95% CI=1.59-3.29). CONCLUSIONS: Young adults in California recognized audiovisual and image-based online e-cigarette marketing. Such recognition may lead to positive e-cigarette-related attitudes and behavioral intentions, especially among never users. Future research should examine the causal relationship between the associations found in this study. Findings may inform the development and evaluation of psychometrically valid measures of online e-cigarette marketing exposures. IMPLICATIONS: Recognition of online e-cigarette marketing stimuli was associated with greater odds of reporting appeal and benefits of e-cigarettes, purchase intentions, and lifetime e-cigarette use among all participants, and susceptibility to use e-cigarettes among never users. These findings may motivate the development and evaluation of psychometrically valid measures of online e-cigarette marketing exposures.

Enhancing Vascular Health and Lowering Blood Pressure in Spontaneously Hypertensive Rats through Syrah Grape (Vitis vinifera) Pomace: The Role of Phenolic Compounds.

BACKGROUND: The beneficial properties of wine by-products include actions that help prevent and treat cardiovascular conditions such as hypertension, primarily due to their antioxidant effects. Novel pharmacotherapies are being developed to treat arterial hypertension, including investigations into natural products exhibiting biological activity, necessitating rigorous evaluation of their efficacy and safety. This study aimed to identify and quantify phenolic compounds in Syrah (Vitis vinifera) grapes grown in the Brazilian Cerrado and their presence in winemaking by-products. It also examined the effects of grape pomace on blood pressure. METHODS: Fresh grapes, pomace, and lees, were subjected to spectrophotometric determination of total phenolic compounds, followed by identification and quantification using HPLC-DAD-ESI-MSn. Normotensive male rats (Wistar) and spontaneously hypertensive rats (SHR) received grape pomace-enriched (150 or 300 mg/kg/day, 14 days) or standard chow. Indirect arterial pressure was assessed, while vascular reactivity was evaluated in mesenteric resistance arteries. RESULTS: Pomace samples exhibited higher total phenolic compound concentrations than grapes or lees. Seven derivatives of hydroxycinnamic acids and twenty-one flavonols were identified. Quercetin-3-glucoside and ethyl caffeate were the most abundant phenolic compounds. Grape pomace-enriched chow demonstrated a dose-dependent hypotensive effect in rats. CONCLUSION: the abundance of flavonols and hydroxycinnamic acids, combined with their hypotensive effects, underscores the therapeutic potential of fine wine-making by-products produced in the Brazilian Cerrado.

Maternal and neonatal outcomes associated with breech presentation in planned community (home and birth center) births in the United States: A prospective observational cohort study.

OBJECTIVE: Investigate maternal and neonatal outcomes associated with breech presentation in planned community births in the United States, including outcomes associated with types of breech presentation (i.e., frank, complete, footling/kneeling). DESIGN: Secondary analysis of prospective cohort data from a national perinatal data registry (MANA Stats). SETTING: Planned community birth (homes and birth centers), United States. SAMPLE: Individuals with a term, singleton gestation (N = 71,943) planning community birth at labor onset. METHODS: Descriptive statistics to calculate associations between types of breech presentation and maternal and neonatal outcomes. MAIN OUTCOME MEASURES: Maternal: intrapartum/postpartum transfer, hospitalization, cesarean, hemorrhage, severe perineal laceration, duration of labor stages and membrane rupture Neonatal: transfer, hospitalization, NICU admission, congenital anomalies, umbilical cord prolapse, birth injury, intrapartum/neonatal death. RESULTS: One percent (n = 695) of individuals experienced breech birth (n = 401, 57.6% vaginally). Most fetuses presented frank breech (57%), with 19% complete, 18% footling/kneeling, and 5% unknown type of breech presentation. Among all breech labors, there were high rates of intrapartum transfer and cesarean birth compared to cephalic presentation (OR 9.0, 95% CI 7.7-10.4 and OR 18.6, 95% CI 15.9-21.7, respectively), with no substantive difference based on parity, planned site of birth, or level of care integration into the health system. For all types of breech presentations, there was increased risk for nearly all assessed neonatal outcomes including hospital transfer, NICU admission, birth injury, and umbilical cord prolapse. Breech presentation was also associated with increased risk of intrapartum/neonatal death (OR 8.5, 95% CI 4.4-16.3), even after congenital anomalies were excluded. CONCLUSIONS: All types of breech presentations in community birth settings are associated with increased risk of adverse neonatal outcomes. These research findings contribute to informed decision-making and reinforce the need for breech training and research and an increase in accessible, high-quality care for planned vaginal breech birth in US hospitals.

Exploring sex differences in blood-based biomarkers following exhaustive exercise using bioinformatics analysis.

This study examined the acute effects of exercise testing on immunology markers, established blood-based biomarkers, and questionnaires in endurance athletes, with a focus on biological sex differences. Twenty-four healthy endurance-trained participants (16 men, age: 29.2± 7.6 years, maximal oxygen uptake ( V ˙ O 2 max ): 59.4 ± 7.5 ml · min-1 · kg-1; 8 women, age: 26.8 ± 6.1 years, V ˙ O 2 max : 52.9 ± 3.1 ml · min-1 · kg-1) completed an incremental submaximal exercise test and a ramp test. The study employed exploratory bioinformatics analysis: mixed ANOVA, k-means clustering, and uniform manifold approximation and projection, to assess the effects of exhaustive exercise on biomarkers and questionnaires. Significant increases in biomarkers (lymphocytes, platelets, procalcitonin, hemoglobin, hematocrit, red blood cells, cell-free DNA (cfDNA)) and fatigue were observed post-exercise. Furthermore, differences pre- to post-exercise were observed in cytokines, cfDNA, and other blood biomarkers between male and female participants. Three distinct groups of athletes with differing proportions of females (Cluster 1: 100% female, Cluster 2: 85% male, Cluster 3: 37.5% female and 65.5% male) were identified with k-means clustering. Specific biomarkers (e.g., interleukin-2 (IL-2), IL-10, and IL-13, as well as cfDNA) served as primary markers for each cluster, potentially informing individualized exercise responses. In conclusion, our study identified exercise-sensitive biomarkers and provides valuable insights into the relationships between biological sex and biomarker responses.

Variations in colostrum metabolite profiles in association with sow parity.

Information about the full spectrum of metabolites present in porcine colostrum and factors that influence metabolite abundances is still incomplete. Parity number appears to modulate the concentration of single metabolites in colostrum. This study aimed to 1) characterize the metabolome composition and 2) assess the effect of parity on metabolite profiles in porcine colostrum. Sows (n = 20) were divided into three parity groups: A) sows in parity 1 and 2 (n = 8), B) sows in parity 3 and 4 (n = 6), and C) sows in parity 5 and 6 (n = 6). Colostrum was collected within 12 h after parturition. A total of 125 metabolites were identified using targeted reversed-phase high-performance liquid chromatography-tandem mass spectrometry and anion-exchange chromatography-high resolution mass spectrometry. Gas chromatography additionally identified 19 fatty acids (FAs). Across parities, colostrum was rich in creatine and creatinine, 1,3-dioleyl-2-palmitatoylglycerol, 1,3-dipalmitoyl-2-oleoylglycerol, and sialyllactose. Alterations in colostrum concentrations were found for eight metabolites among parity groups (P < 0.05) but the effects were not linear. For instance, colostrum from parity group C comprised 75.4% more valine but 15.7%, 34.1%, and 47.9% less citric, pyruvic, and pyroglutamic acid, respectively, compared to group A (P < 0.05). By contrast, colostrum from parity group B contained 39.5% more spermidine than from group A (P < 0.05). Of the FAs, C18:1, C16:0, and C18:2 n6 were the main FAs across parities. Parity affected four FAs (C18:3n3, C14:1, C17:0ai, and C17:1), including 43.1% less α-linolenic acid (C18:3n3) in colostrum from parity group C compared to groups A and B (P < 0.05). Signature feature ranking identified 1-stearoyl-2-hydroxy-sn-glycero-3-phosphatidylcholine and the secondary bile acid hyodeoxycholic acid as the most discriminative metabolites, showing a higher variable importance in the projection score in colostrum from parity group A than from groups B and C. Overall, results provided a comprehensive overview about the metabolome composition of sow colostrum. The consequences of the changes in colostrum metabolites with increasing parity for the nutrient supply of the piglets should be investigated in the future. The knowledge gained in this study could be used to optimize feeding strategies for sows.

Guideline-Concordant Surgical Care for Lobular Versus Ductal Inflammatory Breast Cancer.

INTRODUCTION: Quality of surgical care is understudied for lobular inflammatory breast cancer (IBC), which is less common, more chemotherapy-resistant, and more mammographically occult than ductal IBC. We compared guideline-concordant surgery (modified radical mastectomy [MRM] without immediate reconstruction following chemotherapy) for lobular versus ductal IBC. METHODS:  Female individuals with cT4dM0 lobular and ductal IBC were identified in the National Cancer Database (NCDB) from 2010-2019. Modified radical mastectomy receipt was identified via codes for "modified radical mastectomy" or "mastectomy" and "≥10 lymph nodes removed" (proxy for axillary lymph node dissection). Descriptive statistics, chi-square tests, and t-tests were used. RESULTS: A total of 1456 lobular and 10,445 ductal IBC patients were identified; 599 (41.1%) with lobular and 4859 (46.5%) with ductal IBC underwent MRMs (p = 0.001). Patients with lobular IBC included a higher proportion of individuals with cN0 disease (20.5% lobular vs. 13.7% ductal) and no lymph nodes examined at surgery (31.2% vs. 24.5%) but were less likely to be node-negative at surgery (12.7% vs. 17.1%, all p < 0.001). Among those who had lymph nodes removed at surgery, patients with lobular IBC also had fewer lymph nodes excised versus patients with ductal IBC (median [interquartile range], 7 (0-15) vs. 9 (0-17), p = 0.001). CONCLUSIONS: Lobular IBC patients were more likely to present with node-negative disease and less likely to be node-negative at surgery, despite having fewer, and more frequently no, lymph nodes examined versus ductal IBC patients. Future studies should investigate whether these treatment disparities are because of surgical approach, pathologic assessment, and/or data quality as captured in the NCDB.

Synthesis and Assay of Vibrio Quorum Sensing Inhibitors.

Bacteria detect local population numbers using quorum sensing, a method of cell-cell communication broadly utilized to control bacterial behaviors. In Vibrio species, the master quorum sensing regulators LuxR/HapR control hundreds of quorum sensing genes, many of which influence virulence, metabolism, motility, and more. Thiophenesulfonamides are potent inhibitors of LuxR/HapR that bind the ligand pocket in these transcription factors and block downstream quorum sensing gene expression. This class of compounds served as the basis for the development of a set of simple, robust, and educational procedures for college students to assimilate their chemistry and biology skills using a CURE model: course-based undergraduate research experience. Optimized protocols are described that comprise three learning stages in an iterative and multi-disciplinary platform to engage students in a year-long CURE: (1) design and synthesize new small molecule inhibitors based on the thiophenesulfonamide core, (2) use structural modeling to predict binding affinity to the target, and (3) assay the compounds for efficacy in microbiological assays against specific Vibrio LuxR/HapR proteins. The described reporter assay performed in E. coli successfully predicts the efficacy of the compounds against target proteins in the native Vibrio species.