Scholarly Works, Virginia Tech Carilion School of Medicine (VTCSOM)

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Cobalt Protoporphyrin IX Attenuates Antibody-Mediated, Complement-Dependent Podocyte Injury: Role of Cobalt and Porphyrin Moieties
Lianos, Elias A.; Phung, Gia Nghi; Zhou, Jianping; Sharma, Mukut (MDPI, 2025-02-23)
Metalloporphyrins (MPs) that induce heme oxygenase (HO)-1 were shown to attenuate complement-mediated glomerular injury, with cobalt protoporphyrin IX (CoPPIX) being the most effective. To decipher the efficacy between CoPPIX and its constituents (Co, PPIX), we compared the outcomes of treatment with each in a rat model of complement-dependent immune injury of glomerular epithelial cells (podocytes). Outcomes were correlated with HO-1 induction and expression levels of complement C3 and of the complement activation regulators (CARs) cluster of differentiation (CD)55, CD59, and CR1-related gene y protein product (Crry). Podocyte injury was induced in rats following a single injection of the complement-fixing antibody against the podocyte antigen, Fx1A. CoPPIX or its constituents, cobaltous chloride (CoCl₂) and protoporphyrin IX (PPIX), were injected prior to and on alternate days thereafter. Urine was assessed for protein excretion and kidney cortex samples were processed for histopathology and assessment of target gene mRNA and protein levels using digital polymerase Chain Reaction (dPCR) and capillary-based Western blot analysis. The anti-Fx1A antibody caused proteinuria and podocyte injury. Treatment with the full CoPPIX chelate reduced proteinuria but treatment with either CoCl₂ or PPIX did not. CoPPIX treatment potently induced HO-1 and reduced tissue C3 mRNA and protein levels. It also increased CD55, CD59, and Crry mRNA, with an inconsistent effect on protein levels. The Co moiety was required for HO-1 induction but not for the decrease in C3. This decrease did not significantly correlate with the effects of CoPPIX treatment on CD55 protein levels. Chelation of cobalt to PPIX enhanced its potency to induce HO-1 but reduced that on CD55 induction. These observations distinguish between the effects of CoPPIX and its constituents on proteinuria consequent to complement-mediated podocyte injury and underlying mediators and identify this MP as a potential disease-modifying agent.
Training School-Based Health Clinicians in New Mexico Regarding Adverse Childhood Experiences
Katzman, Joanna G.; Tomedi, Laura E.; Chari, Krishna; Pandey, Navin; Del Fabbro, Anilla; Ramos, Mary; Kazhe-Dominguez, Briana (MDPI, 2025-03-14)
Background: Adverse childhood experiences (ACEs) are potentially traumatic experiences that may promote poor mental health, including substance use and suicidality, as well as chronic pain. Telementoring may be used to provide education to school-based health center (SBHC) clinicians and other health professionals in the community to identify and support youth with ACEs. Methods: This study was an evaluation of the novel ACEs ECHO telementoring program, which incorporates didactics, case-based learning, and a community of practice to serve school-based health clinicians in New Mexico, a rural state with a high prevalence of ACEs. Results: In the program’s first two years, there were 704 unique participants, including SBHC clinicians from 25 of New Mexico’s 33 counties. The pre/post survey demonstrated that the participants reported increases in knowledge in identifying children that experienced ACEs (4.3 versus 3.7, p = 0.001) and confidence in supporting children who may be at high risk (4.1 versus 3.3, p = 0.001) compared with before they began attending the ACEs ECHO program. The participants also reported that they felt more hopeful that they could help youth with ACEs (4.2 versus 3.3, p = 0.001). Conclusions: The ACEs ECHO telementoring program may be considered for other rural states and globally as a capacity-building model to educate SBHC clinicians and other health professionals to identify youth at risk for adverse childhood experiences.
Building a health systems science bridge between medical school and the clinical learning environment via a pilot faculty development cohort program
Harendt, Sarah M.; Allison-Jones, Lisa; Rudd, Mariah J.; Karp, Natalie E.; Parker, Sarah H.; Whicker, Shari A. (2025-03-18)
Background: Clinical faculty development focused on Health Systems Science (HSS) is crucial for integrating HSS concepts into medical education. The 2021 HSSIP Faculty Development program was created to support faculty in effectively creating and incorporating comprehensive HSS content into the clerkship experience. Methods: Nine clinical champions, selected for their diverse backgrounds and interest in HSS, participated from November 2021 through October 2022 in monthly day-long, in-person workshops, and bi-monthly self-directed sessions, covering both HSS domains and foundational learning in curriculum development. Using a community of practice model, clinical champions gained expertise in HSS domains and developed curricula throughout the year-long program. Evaluation methods included surveys and feedback, focusing on satisfaction, self-efficacy, and curricular content creation. Results: Post-engagement surveys showed increased comfort in teaching HSS content, with significant improvement in specific areas. Participants valued learning from experts and collaborating with peers but found virtual sessions challenging. Despite systemic challenges and time constraints, clinical champions successfully created and implemented HSS-focused curricular content. They also contributed to broader HSS education efforts, presenting scholarly work and integrating HSS into various educational activities. Conclusions: This study showcases an innovative approach to preparing faculty to integrate HSS into clinical education. Key lessons included the value of subject matter experts, community engagement, and the challenges of virtual participation. Despite limitations such as low response numbers and context-specific results, the program demonstrated the potential for broad HSS integration. Further research with more participants and more rigorous data collection protocols is needed to more fully understand the generalizability of such an innovation. The initiative serves as a model for other academic health centers.
A unique case of herpetic keratitis manifesting as recurrent preseptal cellulitis
Miller, Emily; Ward, Maxwell; Fazili, Tasaduq; Bansal, Ekta (Elsevier, 2025-02-09)
Preseptal cellulitis is typically caused by nasopharyngeal bacteria and can usually be treated with empiric antibiotics. We present a case of herpes simplex virus (HSV) 1 keratitis manifesting as recurrent and treatment refractory preseptal cellulitis. This is a rare presentation that is infrequently reported in the literature. Due to the potential for permanent vision loss, it is important to consider herpes viruses as an etiology in immunocompromised patients with preseptal cellulitis not responding to standard treatment.
Extent of Myometrial Resection With Various Surgical Methods for Endometrial Polypectomy Procedures
Evans-Hoeker, Emily; Millner, Adrienne; Lee, Grace; Perry, Ryan; Perry, Ryan; Kar, Ayesha; Swaroop, Meyha; Locklear, Tonja; Newman, Brian; Casey, James (Wolters Kluwer Health, Inc., 2024-09)
OBJECTIVE: To assess whether the frequency and extent of myometrial resection differs among surgical methods commonly used for endometrial polypectomy. METHODS: We conducted a retrospective cohort study of pathology samples from polypectomy procedures performed on patients 18–50 years of age. Samples were reevaluated by a blinded pathologist to assess the following primary outcome measures: presence and percentage of myometrium on the pathology sample, prevalence of isolated myometrium, and depth of myometrial resection. Data were evaluated using Fisher exact test and Kruskal-Wallis test, followed by multiple comparisons analysis. To maintain a familywise error rate of 5% across all four primary analyses, the Bonferroni correction method was applied. RESULTS: Of 458 pathology samples, 21.8% were obtained using hysteroscopic morcellators, 11.1% were obtained with hysteroscopic scissors, and 67.0% were obtained with hysteroscopy with dilation and curettage (D&C). Hysteroscopic morcellation demonstrated a higher prevalence of myometrium (58.0% vs 9.8% and 15.3%, for hysteroscopic scissors and hysteroscopy with D&C, respectively; P,.001), a larger percentage of pathology samples with more than 25% myometrium (26.0% vs 4.0% and 0.6%, respectively; P,.001), and a higher prevalence of isolated myometrium compared with hysteroscopy with D&C (11.0% vs 0.7%; P,.001). CONCLUSION: The presence and proportion of myometrium in polypectomy samples obtained using hysteroscopic morcellators was significantly higher compared with hysteroscopic scissors and hysteroscopy with D&C.
Diabetes Performance Improvement Program With Continuous Glucose Monitoring, Pharmacist Intervention, and Team Management
Behnke, Andrew; Christopher G. Parkin (Elmer Press, 2024-10-31)
The growing prevalence of diabetes in the USA continues to be a significant public health concern. A significant proportion of patients with type 2 diabetes (T2D) have elevated glucose levels, as evidenced by a glycated hemoglobin (HbA1c) level > 9.0%. Persistent hyperglycemia results in the development of chronic macrovascular and microvascular complications. Previous strategies to assist this high-risk population in achieving optimal glycemic control have not been as successful as desired. As the demand for healthcare providers and services continues to grow at an unprecedented pace, the USA is facing a national deficit in physicians, nurse practitioners, and physician assistants. Conversely, the number of pharmacists is projected to increase at a rate of 3% annually over the next three decades. Studies have demonstrated that pharmacist involvement in diabetes patient management has resulted in improvements in HbA1c, lowering of low-density lipoprotein (LDL)-cholesterol levels, and achievement of blood pressure targets. This suggests the potential for pharmacists to play a key role in narrowing the gap. We implemented a Diabetes Performance Improvement Program (DPIP) that facilitates a comprehensive lifestyle intervention designed to improve diabetes management and outcomes. The DPIP care team comprises endocrinologists, certified diabetes educators, pharmacists, and supporting staff. The intervention includes utilizing continuous glucose monitoring (CGM) supported by diabetes self-management training (DSMT) and medical nutrition therapy (MNT) delivered by a certified diabetes education specialist (CDES) and registered dietitian (RD). This article reviews the evidence supporting the use of an interdisciplinary team-based approach to diabetes care, describes the DPIP components, and provides guidance for implementing the program in clinic-community settings.
Effectiveness of Intraoperative Ketorolac in Outpatient Breast Surgery: A Double-blinded Prospective Randomized Controlled Trial
Choi, Joowon M.; Rodriguez, Jose D.; Saccocci, Michael A.; Shafer, Robert P.; Feldmann, Mark E.; Moyer, Kurtis E.; Thompson, James T. (Wolters Kluwer Health, 2025-02-17)
Background: The use of nonnarcotic analgesics, such as ketorolac, has been shown to reduce postoperative pain and opioid consumption. This double-blinded randomized trial is designed to assess the efficacy of intraoperative ketorolac in reducing postoperative narcotic use in outpatient breast reconstruction and reduction procedures. Methods: This study is a prospective double-blinded randomized controlled trial. Adult patients, 18-64 years of age, undergoing breast surgery were randomized to receive 15 mg of ketorolac, 30 mg of ketorolac, or a placebo dose of saline. Patients' opioid requirements in the postoperative anesthesia care unit and postoperative opioid utilization and pain scores were collected through a daily survey. Postoperative hematomas were assessed before discharge and at subsequent follow-up visits for a period of 14 days. Results: Of the 63 patients included in the study, 31 patients underwent delayed reconstruction following mastectomy and 35 patients underwent breast reduction surgery. Patients who received 30 mg of ketorolac had the fastest pain resolution (P<0.05). The rate of opioid discontinuance was the fastest overall in patients who received 15 mg of ketorolac (rate = -0.072) when compared with the 30-mg ketorolac group (rate = -0.071) and the placebo group (rate = -0.065). Total opioid usage in the postoperative anesthesia care unit was not statistically different across the 3 groups. Only 1 patient developed a hematoma in the 15-mg ketorolac group. Conclusions: This study demonstrates that a single dose of intraoperative ketorolac was associated with reduced opioid usage and postoperative pain. However, due to the study size, the difference in hematoma rate was not statistically significant.
Point-of-Care Ultrasound Transmission for Remote Interpretation in Austere Environments
Haines, Carver M.; Waasdorp, Christopher P.; Lockhart, Ellen R.; Lareau, Stephanie A. (Sage, 2023-06-29)
Introduction: Point–of-care ultrasound (POCUS) is used in wilderness medicine and could potentially be the only imaging modality available. Cellular and data coverage is often lacking in remote areas, limiting image transmission. This study evaluates the viability of transmitting POCUS images from austere environments using slow-scan television (SSTV) image transmission methods over very-high-frequency (VHF) hand-held radio units for remote interpretation. Methods: Fifteen deidentified POCUS images were selected and encoded into an SSTV audio stream by a smartphone and transmitted over a VHF radio. A second radio and smartphone 1 to 5 mi away received and decoded the signals back into images. The original images and transmitted images were randomized into a survey graded by emergency medicine physicians using a standardized ultrasound quality assurance scoring scale (1–5 points). Results: The difference in mean scores between the original image and transmitted image showed a 3.9% decrease in transmitted image scores, with P <0.05 on a paired t test; however, this is not likely a clinically significant decrease. Comparing transmitted images using different SSTV encodings and distances ranging up to 5 mi, 100% of survey respondents determined the images to be clinically usable. This dropped to 75% when significant artifacts were introduced. Conclusions: Slow-scan television image transmission is a viable option for transmitting ultrasound images in remote areas where more modern forms of communication are unavailable or not practical. Slow-scan television may have potential as another data transmission option in the wilderness, such as electrocardiogram tracings.
Timing and Predictors of Upper Extremity Peripheral Nerve Reconstruction
Gray, Kelsey M.; Burkat, Andrzej J.; Arney, Lucas A.; Peterman, Nicholas J.; Mandala, Sahith R.; Capito, Anthony E. (Elsevier, 2025-02)
Primary neurorrhaphy is the preferred reconstruction modality over nerve grafting, especially for motor nerves. The main limitation to primary repair is often dictated by tension secondary to increased nerve defect length. A retrospective review was conducted of sharp transections of mixed motor and purely sensory nerves in the upper extremity to assess factors influencing defect length. Two groups of either primary repair or nerve graft/conduit were created for comparison. 71 injured mixed motor nerves and 224 injured sensory nerves were included for analysis. There were no significant differences in patient demographics between groups. The primary repair group had a significantly shorter time interval between injury and surgical fixation when compared to the conduit/graft group. Conduit or graft technique was associated with a significantly larger tissue gap after preparation of the nerve ends. Our data suggest the best chance of primary repair is within 3 days for mixed nerves and within 7 days for purely sensory. A total of 167 nerve reconstructions were included in a random forest plot, which demonstrated nerve defect size to be influenced by days from injury, type of nerve injured, age, and hypertension. A publicly available 4-feature calculator, NERVE (Nerve Evaluation and Retraction Variability Estimator), was developed from the forest plot to predict a patient's nerve deficit ± 3.78 mm on average, R2 = 0.89. This calculator could aid surgeons with surgical planning for the potential need of grafts or conduits for reconstruction.
Curriculum Guidelines for Wilderness Medicine Medical Student Electives: 2025 Update
Plash, Walker B.; Leiva, Daniel F.; Watkins, Kevin D.; Gardner, Justin M.; Comp, Geoffrey; Lareau, Stephanie A. (SAGE Publications, 2025-02-21)
Wilderness medicine elective rotations for graduate medical students are gaining popularity. The number of electives continues to grow, each with varying curriculum, format, and means of assessment. Previous curriculum guidelines attempted to standardize the knowledge-based competency for medical students in this field. Concurrently, medical education has evolved, emphasizing learner-centric and outcome-based observable competencies. Competencies based on individual qualities have since been complemented by practice-specific activities called entrustable professional activities (EPAs), which may consist of smaller observable practice activities (OPAs). This has allowed educators to use a holistic approach to determine that an individual can be fully entrusted to carry out an unsupervised activity. We surveyed current graduate-level wilderness medicine elective directors to determine expert panel recommendations for the EPAs of wilderness medicine for graduate medical students. The aim was to create EPAs and OPAs that experts deem fundamental for a wilderness medicine elective rotation and align them under the framework of entrustable practice in medical education. By mapping wilderness medicine EPAs and OPAs to competencies, we can better measure developmental progression and degree of entrustment in graduate wilderness medicine electives.
Examination of the moderating effect of race on the relationship between Vitamin D status and COVID-19 test positivity using propensity score methods
Crandell, Ian; Rockwell, Michelle S.; Whitehead, Phyllis B.; Carter, Kimberly Ferren; Hanlon, Alexandra L. (Journal of the American College of Nutrition, 2021-09-02)
Introduction: With a well-established role in inflammation and immune function, vitamin D status has emerged as a potential factor for coronavirus disease-2019 (COVID-19). Objective: The purpose of this study was to evaluate the moderating effect of race on the relationship between vitamin D status and the risk of COVID-19 test positivity, and to compare propensity score (PS) model results to those obtained from classical bivariate and multivariable models, which have primarily comprised the literature to date. Methods: Electronic health record (EHR) data from TriNetX (unmatched n = 21,629; matched n = 16,602) were used to investigate the effect of vitamin D status, as measured by 25-hydroxyvitamin D [25(OH)D], on the odds of experiencing a positive COVID-19 test using multivariable logistic regression models with and without PS methodology. Results: Having normal (≥ 30 ng/mL) versus inadequate 25(OH)D (< 30 ng/mL) was not associated with COVID-19 positivity overall (OR = 0.913, p = 0.18), in White individuals (OR = 0.920, p = 0.31), or in Black individuals (OR = 1.006, p = 0.96). When 25(OH)D was analyzed on a continuum, a 10 ng/mL increase in 25(OH)D lowered the odds of having a positive COVID-19 test overall (OR = 0.949, p = 0.003) and among White (OR = 0.935, p = 0.003), but not Black individuals (OR = 0.994, p = 0.75). Conclusions: Models which use weighting and matching methods resulted in smaller estimated effect sizes than models which do not use weighting or matching. These findings suggest a minimal protective effect of vitamin D status on COVID-19 test positivity in White individuals and no protective effect in Black individuals.
CogWatch: An open-source platform to monitor physiological indicators for cognitive workload and stress
Dankovich, Louis J.; Joyner, Janell S.; He, William; Sesay, Ahmad; Vaughn-Cooke, Monifa (Elsevier, 2024-05-23)
Cognitive workload is a measure of the mental resources a user is dedicating to a given task. Low cognitive workload produces boredom and decreased vigilance, which can lead to an increase in response time. Under high cognitive workload the information processing burden of the user increases significantly, thereby compromising the ability to effectively monitor their environment for unexpected stimuli or respond to emergencies. In cognitive workload and stress monitoring research, sensors are used to measure applicable physiological indicators to infer the state of user. For example, electrocardiography or photoplethysmography are often used to track both the rate at which the heart beats and variability between the individual heart beats. Photoplethysmography and chest straps are also used in studies to track fluctuations in breathing rate. The Galvanic Skin Response is a change in sweat rate (especially on the palms and wrists) and is typically measured by tracking how the resistance of two probes at a fixed distance on the subject's skin changes over time. Finally, fluctuations in Skin Temperature are typically tracked with thermocouples or infrared light (IR) measuring systems in these experiments. While consumer options such a smartwatches for health tracking often have the integrated ability to perform photoplethysmography, they typically perform significant processing on the data which is not transparent to the user and often have a granularity of data that is far too low to be useful for research purposes. It is possible to purchase sensor boards that can be added to Arduino systems, however, these systems generally are very large and obtrusive. Additionally, at the high end of the spectrum there are medical tools used to track these physiological signals, but they are often very expensive and require specific software to be licensed for communication. In this paper, an open-source solution to create a physiological tracker with a wristwatch form factor is presented and validated, using conventional off-the-shelf components. The proposed tool is intended to be applied as a cost-effective solution for research and educational settings.
Large language models: a primer and gastroenterology applications
Shahab, Omer; El Kurdi, Bara; Shaukat, Aasma; Nadkarni, Girish; Soroush, Ali (Sage, 2024-02-22)
Over the past year, the emergence of state-of-the-art large language models (LLMs) in tools like ChatGPT has ushered in a rapid acceleration in artificial intelligence (AI) innovation. These powerful AI models can generate tailored and high-quality text responses to instructions and questions without the need for labor-intensive task-specific training data or complex software engineering. As the technology continues to mature, LLMs hold immense potential for transforming clinical workflows, enhancing patient outcomes, improving medical education, and optimizing medical research. In this review, we provide a practical discussion of LLMs, tailored to gastroenterologists. We highlight the technical foundations of LLMs, emphasizing their key strengths and limitations as well as how to interact with them safely and effectively. We discuss some potential LLM use cases for clinical gastroenterology practice, education, and research. Finally, we review critical barriers to implementation and ongoing work to address these issues. This review aims to equip gastroenterologists with a foundational understanding of LLMs to facilitate a more active clinician role in the development and implementation of this rapidly emerging technology.
What Is the Significance of Placental Lakes in Pregnancy? A Historic Literature Review
Choi-Klier, Joanna; Masters, Stephanie; Lewis, Danielle; Taylor, Kaitlyn; Magann, Everett F. (MDPI, 2025-02-14)
Background/Objectives: The presence of placental lakes has been recognized on obstetric ultrasounds for many years, although their influence on pregnancy and perinatal outcomes remains uncertain. Most studies evaluating outcomes are small and many outcomes are conflicting. The question remains whether placental lakes affect pregnancy outcomes and, if so, how and under what circumstances? The purpose of this review was to determine the incidence, diagnosis, pathology, management, and pregnancy outcomes to determine the influence of an isolated lake versus the influence of a lake with the presence of other factors on pregnancy and perinatal outcomes. Methods: Electronic databases (PubMed, OVID, CINAHI, Embase, and Web of Science) were searched. The only limitation was the abstract/paper had to be in English. The search years were 1980–2023. The search terms included “placenta lake” AND “pregnancy outcomes”. Results: Of 323 abstracts identified, 26 full articles were selected as the basis of this review. A number of adverse outcomes have been reported with placenta lakes, including hypertensive disorders of pregnancy, fetal growth restriction, and intrauterine fetal demise. Other studies reported no adverse outcomes. A number of factors in addition to the placental lake, such as the size of the lake, number of lakes, and presence of a thick placenta, might increase the risk of adverse outcomes. Conclusions: Unfavorable pregnancy outcomes may be related to placental lakes, particularly if the lakes are multiple and large and the placenta is thick. Additional large studies are needed to determine if antenatal surveillance is helpful.
Percutaneous Thrombovegectomy as an Alternative to Surgery for Tricuspid Valve Endocarditis
Reddy, V. Seenu; Zwischenberger, Brittany A.; Williams, Adam R.; Rowe, Joseph F.; Subramanian, Sreekumar; Kingeter, Adam; Wright, Justin; Joseph, Mark (Elsevier, 2024-04-26)
Background: Undergoing an urgent valve surgical procedure to treat patients with tricuspid valve endocarditis carries a high risk of operative morbidity and mortality. Use of a percutaneous vacuum-assisted system to treat tricuspid valve endocarditis is an alternative to surgical procedures. Methods: This study retrospectively analyzed data from 187 transcatheter vacuum-assisted aspiration procedures performed in 177 patients with tricuspid valve vegetations at 3 different centers between 2017 and April 2022. The device was deployed through the internal jugular or femoral vein into the right atrium by using transesophageal echocardiography and fluoroscopy guidance with the return cannula placed in the femoral vein. The following data were analyzed: intravascular material aspirated, collected in an external filter, and cultured; hospital length of stay; procedural complications; blood culture clearance; and tricuspid regurgitation. Results: The mean age of participants was 35.5 ± 10.8 years (range, 18-79 years). A total of 107 procedures (57.2%) were performed in female patients, and 163 (87.2%) procedures were performed in intravenous drug users. All patients survived the procedure, and there were no procedural complications. The average length of stay was 26.8 ± 18.5 days (range, 1-96 days). Most preoperative positive blood cultures showed Staphylococcus aureus (80.3%), with postoperative cultures converting to negative in 103 (70.1%) of 147 procedures. Tricuspid regurgitation remained unchanged after 95 (50.8%) procedures and worsened after 40 (21.4%) procedures. Conclusions: Percutaneous vacuum-assisted aspiration system provides a safe alternative to urgent tricuspid valve surgical procedures for removal of vegetations, especially in patients with endocarditis. Initial vegetation debulking can expedite clearance of blood cultures while avoiding major cardiac surgery operations and implantation of prosthetic valves in these high-risk patients.
MCU expression in hippocampal CA2 neurons modulates dendritic mitochondrial morphology and synaptic plasticity
Pannoni, Katy E.; Fischer, Quentin S.; Tarannum, Renesa; Cawley, Mikel L.; Alsalman, Mayd M.; Acosta, Nicole; Ezigbo, Chisom; Gil, Daniela V.; Campbell, Logan A.; Farris, Shannon (Nature Research, 2025-02-06)
Neuronal mitochondria are diverse across cell types and subcellular compartments in order to meet unique energy demands. While mitochondria are essential for synaptic transmission and synaptic plasticity, the mechanisms regulating mitochondria to support normal synapse function are incompletely understood. The mitochondrial calcium uniporter (MCU) is proposed to couple neuronal activity to mitochondrial ATP production, which would allow neurons to rapidly adapt to changing energy demands. MCU is uniquely enriched in hippocampal CA2 distal dendrites compared to proximal dendrites, however, the functional significance of this layer-specific enrichment is not clear. Synapses onto CA2 distal dendrites readily express plasticity, unlike the plasticity-resistant synapses onto CA2 proximal dendrites, but the mechanisms underlying these different plasticity profiles are unknown. Using a CA2-specific MCU knockout (cKO) mouse, we found that MCU deletion impairs plasticity at distal dendrite synapses. However, mitochondria were more fragmented and spine head area was diminished throughout the dendritic layers of MCU cKO mice versus control mice. Fragmented mitochondria might have functional changes, such as altered ATP production, that could explain the structural and functional deficits at cKO synapses. Differences in MCU expression across cell types and circuits might be a general mechanism to tune mitochondrial function to meet distinct synaptic demands.
The surgical time-out: the relationship between perceptions of a safety-task anchor and surgical team workflow
Zagarese, Vivian J.; Hernandez, Ivan; Hauenstein, Neil M. A.; Foti, Roseanne J.; Parker, Sarah H. (2025-02-05)
Background The surgical time-out is a critical safety measure used in the operating room (OR). We examined the mediating relationship of the length of the time-out between team perceived usefulness of the time-out, and the rate at which the circulating nurse left the OR to retrieve instruments. Methods 60 cardiac surgical teams were observed performing their work. The length of the time-out and the rate at which the circulating nurse left the OR was obtained by observation of the surgical team. We administered a survey with a 7-point Likert scale to assess the surgical staff’s perceived usefulness of the time-out at the end of the surgery. An analysis was conducted to test if length of the time-out mediated the relationship between perceived usefulness of the time-out and rate at which the nurse leaves the OR to retrieve an instrument useful for the surgery. Results The relationship of the length of the time-out with the rate at which the nurse leaves the OR was non-significant (β = 0.089, p = .496). However, the relationship between perceived usefulness of the time-out with the length of the time-out was significant (β = 0.346, p < .05) and the effect between perceived usefulness of the time-out and the rate at which the nurse left the OR was statistically significant (β= − 0.424, p = < 0.001). Conclusion In this study we explore how surgical teams’ attitudes towards the usefulness of the time-out affect its utilization, and how attitudes about time-outs are related to the important process measure of rate at which the circulating nurse leaves the OR. The full mediation model was not supported by the data; however, there appears to be a relationship between the perceived usefulness of the time-out and the rate at which the circulating nurse leaves the OR.
Proteomic insights into breast cancer response to brain cell-secreted factors
Ahuja, Shreya; Lazar, Iuliana M. (Springer, 2024-08-21)
The most devastating feature of cancer cells is their ability to metastasize to distant sites in the body. HER2 + and TN breast cancers frequently metastasize to the brain and stay potentially dormant for years until favorable conditions support their proliferation. The sheltered and delicate nature of the brain prevents, however, early disease detection and effective delivery of therapeutic drugs. Moreover, the challenges associated with the acquisition of brain biopsies add compounding difficulties to exploring the mechanistic aspects of tumor development. To provide insights into the determinants of cancer cell behavior at the brain metastatic site, this study was aimed at exploring the early response of HER2 + breast cancer cells (SKBR3) to factors present in the brain perivascular niche. The neural microenvironment was simulated by using the secretome of a set of brain cells that come first in contact with the cancer cells upon crossing the blood brain barrier, i.e., endothelial cells, astrocytes, and microglia. Cytokine microarrays were used to investigate the secretome mediators of intercellular communication, and proteomic technologies for assessing the changes in the behavior of cancer cells upon exposure to the brain cell-secreted factors. The cytokines detected in the brain secretomes were supportive of inflammatory conditions, while the SKBR3 cells secreted numerous cancer-promoting growth factors that were either absent or present in lower abundance in the brain cell cultures, indicating that upon exposure the SKBR3 cells may have been deprived of favorable conditions for optimal growth. Altogether, the results suggest that the exposure of SKBR3 cells to the brain cell-secreted factors altered their growth potential and drove them toward a state of quiescence, with broader overall outcomes that affected cellular metabolism, adhesion and immune response processes. The findings of this study underscore the key role played by the neural niche in shaping the behavior of metastasized cancer cells, provide insights into the cellular cross-talk that may lead cancer cells into dormancy, and highlight novel opportunities for the development of metastatic breast cancer therapeutic strategies.
Proteomic assessment of SKBR3/HER2+ breast cancer cellular response to Lapatinib and investigational Ipatasertib kinase inhibitors
Karcini, Arba; Mercier, Nicole R.; Lazar, Iuliana M. (Frontiers, 2024-08-29)
Introduction: Modern cancer treatment strategies aim at achieving cancer remission by using targeted and personalized therapies, as well as harnessing the power of the immune system to recognize and eradicate the cancer cells. To overcome a relatively short-lived response due to resistance to the administered drugs, combination therapies have been pursued. Objective: The objective of this study was to use high-throughput data generation technologies such as mass spectrometry and proteomics to investigate the broader implications, and to expand the outlook, of such therapeutic approaches. Specifically, we investigated the systems-level response of a breast cancer cell line model to a mixture of kinase inhibitors that has not been adopted yet as a standard therapeutic regime. Methods: Two critical pathways that sustain the growth and survival of cancer cells, EGFR and PI3K/AKT, were inhibited in SKBR3/HER2+ breast cancer cells with Lapatinib (Tyr kinase inhibitor) and Ipatasertib (Ser/Thr kinase inhibitor), and the landscape of the affected biological processes was investigated with proteomic technologies. Results: Over 800 proteins matched by three unique peptide sequences were affected by exposing the cells to the drugs. The work corroborated the anti-proliferative activity of Lapatinib and Ipatasertib and uncovered a range of impacted cancer-supportive hallmark processes, among which immune response, adhesion, and migration emerged as particularly relevant to the ability of drugs to effectively suppress the proliferation and dissemination of cancer cells. Changes in the expression of key cancer drivers such as oncogenes, tumor suppressors, EMT and angiogenesis regulators underscored the inhibitory effectiveness of drugs on cancer proliferation. The supplementation of Lapatinib with Ipatasertib further affected additional transcription factors and proteins involved in gene expression, trafficking, DNA repair, and development of multidrug resistance. Furthermore, over fifty of the impacted proteins represent approved or investigational targets in the DrugBank database, which through their protein-protein interaction networks can inform the selection of effective therapeutic partners. Conclusion: Altogether, the exposure of SKBR3/HER2+ cells to Lapatinib and Ipatasertib kinase inhibitors uncovered a broad plethora of yet untapped opportunities that can be further explored for enhancing the anti-cancer effects of each drug as well as of many other multi-drug therapies that target the EGFR/ERBB2 and PI3K/AKT pathways.
Medial Femoral Condyle (MFC) Bone Flap
Capito, Anthony E. (2024-12-07)

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