The Effects of Synovial Fluid and Inflammatory Cells on Orthopaedic Implant Alloys

Introduction. Total knee arthroplasty (TKA) is a common surgical procedure used to treat end-stage osteoarthritis. The implants used in TKA typically consist of a Cobalt Chromium Molybdenum (CoCrMo) femoral component and a Titanium Aluminum Vanadium (TiAlV) alloy baseplate. These metal alloys are chosen for their mechanical properties, corrosion resistance, high affinity for bone, and biocompatibility. However, they can be susceptible to mechanical and electrochemical wear, leading to the release of metal ions. Osteoarthritis and inflammation can alter the composition of Synovial Fluid (SF), potentially causing implant corrosion and the release of metal ions into the surrounding tissue. These metal ions can trigger innate and adaptive responses, further enhancing implant corrosion. As the number of primary TKA (PTKA) procedures increases, the incidence of revision surgeries due to implant failure is also expected to rise. Approximately 20% of TKA recipients report dissatisfaction after surgery. To reduce this number, it is crucial to investigate the modes of failure in TKA and their correlation with patient quality of life. Methodology.The study employed a methodology to examine the effects of SF on orthopedic implant alloys. SF samples were collected from patients before their TKA surgery (IRB approval number: 16-04802-XP and 21-08403-XP) and transferred to an electrochemical cell (Bioanalytical Systems, Inc.), in which the metal alloy electrodes served as working electrodes. To obtain the corrosion rates of TiAlV and CoCrMo alloys in each patient SF, passivated rods of ASTM F1537 CoCrMo and ASTM F136 TiAlV alloys were used. The volumes and pH of the collected SF samples were recorded with the electrochemical potential of the metal alloy electrodes in the SF samples against an Ag|AgCl|3M NaCl reference electrode. Patients were contacted 3 months post-op to answer the KOOSJR (Knee injury and Osteoarthritis Outcome Score, Joint Replacement) survey to assess their knee pain, stiffness, and function. After electrochemical testing, samples were stored at -80 °C until the metal ion content in the individual SF samples was determined. To determine the effects of the innate and adaptive responses in vitro on orthopaedic implant metal, IC-21 murine macrophages and D10.G4.1 murine lymphocytes were cultured. Select groups of macrophages were activated using Interferon Gamma (IFNγ) and Lipopolysaccharide (LPS). CoCrMo and TiAlV alloy disks were cut, polished, passivated, and placed into 24 well plates. After seeding the cells, the culture medium was replaced every 24 hours, and the supernatant fluid was collected every day starting on the second day of the experiment. After 30 days, cells were removed from the surface of the alloy specimens, counted, tested for viability, and digested. The metal concentrations found in the supernatant and digested cell mixture were assessed using inductively coupled plasma spectrometry (ICP-MS), conducted at Brooks Applied Labs (Bothwell, WA). The oxygen (oxide) levels on the metal alloy specimen surfaces were determined as percent weight using Scanning Electron Microscopy and Energy Dispersion X-ray Spectroscopy (SEM-EDS). Statistical analysis was conducted using Microsoft Excel (Microsoft, Redmond, WA) and IBM SPSS (Armonk, NY). Results. The open circuit potential (OCP) values ranged from -0.274 to 0.123 V and -0.322 to 0.027 V for CoCrMo and TiAlV respectively. However, no significant association was found between the electrochemical parameters and the KOOSJR scores, indicating no direct correlation between corrosion rates and patient-reported outcomes. The SF volume was found to be a significant factor, with patients having greater SF volumes exhibiting higher KOOSJR scores. Patients with greater than 2 mL SF volumes had significantly higher KOOSJR scores than those who had less than 2 mL SF (p = 0.004). All patients with higher SF pH values (pH values ranged from 7.09 to 8.5) had smaller SF volumes (p \u3c 0.05). Patients with CoCrMo implants and higher pH values had lower OCP (p = 0.002), Rp (p = 0.013), and Ecorr (p = 0.012) values but higher corrosion rates (p = 0.03). No similar relationships were found for patients\u27 SFs with TiAlV alloy implants. No differences in cell counts were found. The macrophages and supernatant were sent for ICPMS (Inductively Coupled Plasma Spectrometry) testing to determine their metal ion concentration. Activated MO + Disks in both alloy groups had elevated metal content compared to non-activated MO + Disk groups. The Activated MO + lymphocytes + Disks had lower metal ion levels compared to Nonactivated MO + lymphocytes + Disks groups for CoCrMo groups and TiAlV groups. Ti, Al, Cr, and Mo metal concentration in the supernatants of the compared groups were the same but Co metal ion levels were significantly higher in Activated + MO + TiAlV disks (p = 0.004) and Nonactivated + MO + TiAlV disks (p = 0.007) groups compared to their control groups (Activated + MO + no disks and Nonactivated + MO + no disks respectively). V metal ion levels were significantly higher in Activated + MO + TiAlV disks (p = 0.007) and Nonactivated + MO + TiAlV disks (p = 0.026) groups compared to their control groups (Activated + MO + no disks and Nonactivated + MO + no disks respectively). SEM (Scanning Electron Microscopy) imaging was used to analyze the surface of the CoCrMo and TiAlV disks. Features with the size of inflammatory cells were identified as valleys. The possibility that these features were the result of the sanding process could be excluded, as the “streaks” crossed in a different direction. Oxide levels were analyzed to detect corrosion for CoCrMo and TiAlV groups with EDS (Energy Dispersive X-ray Spectrometry) SE (Secondary Electron). The Disks + Non-Activated Medium groups for both CoCrMo and TiAlV had significantly higher oxide levels compared to all other groups (p\u3c 0.001). The Activated MO + Lymphocytes + CoCrMo disks group had significantly higher oxide levels than the Nonactivated MO + CoCrMo disks and Activated MO + CoCrMo groups. Conclusions. In conclusion, this study aimed to investigate the electrochemical properties of SF in relation to CoCrMo and TiAlV orthopedic alloy implants and their impact on patient-reported outcomes. The findings contribute to understanding the processes that lead to patient pain and TKA failure. Further research is ongoing to enroll more patients and assess their outcomes up to a year after surgery, aiming to identify protocols that can improve patient satisfaction. The study also explored the effects of macrophages and lymphocytes on the corrosion mechanisms of the implant surfaces, which is essential for reducing the burden on patients and preventing complications such as ALVAL

Solar generation and storage of O2 (a 1 delta g)

An investigation was performed of the technical steps required to design a solar powered oxygen-iodine laser. Singlet delta oxygen is formed upon transfer of energy from selected photoexcited dye molecules to ground state molecular oxygen and then is concentrated and stored as an endoperoxide by reaction with an aromatic hydrocarbon. The endoperoxide, when heated, releases singlet oxygen in high yield thus providing a regenerable source of laser fuel. Energy transfer from dye molecules to molecular oxygen was investigated. When dye molecules were adsorbed to polymer substrates it was observed that the dye became embedded in the polymer matrix. Porphin dyes were incorporated into films of 1,4-dimethyl-2-poly(vinylnaphthalene), 2PVN. An endoperoxide was formed when porphin-doped 2PVN was exposed to visible radiation. This demonstrates the possibility of generating singlet oxygen using solar energy and concentrating and storing it in one simple step. Transport of energy by exciton migration in polycrystalline dye films was also investigated

Evaluation of a Resident-led Residency Preparation Series for Fourth Year Pharmacy Students

Description of Problem: The increased interest in residency programs nationwide has made the application process more competitive and complex. Statement of Innovation: In 2015, Wake Forest Baptist Health (WFBH) created a resident-led residency preparatory series (RPS) to assist advanced pharmacy practice experience (APPE) students in preparing for residency applications. This study sought to evaluate the perceived value of the resident-led RPS by fourth year APPE students. Innovation: This single-center, survey-based, descriptive study aimed to evaluate the perceived impact of a resident-led RPS. All APPE students during the 2016-2017 and 2017-2018 academic years who completed rotations in the Triad region of North Carolina were invited to participate in the RPS. Surveys were sent to eligible students and data was captured for respondents who indicated an interest in pursuing residency and attendance to at least one RPS. Survey questions evaluated satisfaction with the RPS. Survey data was collected and analyzed using Qualtrics©. Critical Analysis:  A total of 84 students were invited to attend the RPS. Thirty-three respondents participated in the RPS and indicated an interest in applying for a residency. The resident-led RPS was consistently well received by the majority of students over the course of two years, with over two-thirds of all respondents finding every session extremely or very useful. The majority of students agreed or strongly agreed with all confidence statements. Conclusion A resident-led RPS resulted in positive student perceptions and increased confidence in the residency application process.   Article Type: Not

Incidence and predictors of left ventricular thrombus formation following acute ST-segment elevation myocardial infarction : a serial cardiac MRI study

Aims: Left ventricular (LV) thrombus is a complication of acute ST-segment elevation myocardial infarction (STEMI). We determined the incidence and predictors of LV thrombus formation using serial cardiac magnetic resonance (CMR) and two-dimensional echocardiography studies. Methods and results: Two hundred and ten patients underwent CMR (median 4 days [IQR 3-7]) and transthoracic echocardiography (median 4 days [IQR 3-7]) early after STEMI presentation with serial follow-up CMR (median 55 days [IQR 46-64]) and echocardiography studies (median 54 days [IQR 45-64]) performed subsequently. The incidence of LV thrombus was 12.3% (26/210) by CMR and 6.2% (13/210) by two-dimensional echocardiography. Echocardiography had 50% sensitivity and 100% specificity for LV thrombus detection compared to CMR. LV thrombus was found in 23.6% of patients with anterior STEMI (22/93). Ischaemic stroke occurred in 1.4% of patients (3/210). Patients with LV thrombus had lower baseline LV ejection fraction (LVEF) (34.9% vs 47.4%, p < 0.001). Microvascular obstruction was more common in patients with LV thrombus (77% vs 39%, p < 0.001). Patients with LV thrombus had increased LV dimensions with larger LV end-diastolic (19 ml [IQR 9-44] vs 6 ml [IQR -4-18], p < 0.001) and end-systolic volumes (10 ml [IQR 0–22] vs -4 ml [IQR -12-4], p < 0.001). Conclusion: CMR increases the detection of LV thrombi which standard echocardiography may underestimate. Serial studies post-STEMI may improve detection of LV thrombus, which is more prevalent in patients with anterior infarction, moderate LV dysfunction and adverse LV remodelling. This subgroup of patients may represent a high-risk group for targeted serial screening with CMR

Visualization of Partial Exocytotic Content Release and Chemical Transport into Nanovesicles in Cells

For decades, "all-or-none"and "kiss-and-run"were thought to be the only major exocytotic release modes in cell-to-cell communication, while the significance of partial release has not yet been widely recognized and accepted owing to the lack of direct evidence for exocytotic partial release. Correlative imaging with transmission electron microscopy and NanoSIMS imaging and a dual stable isotope labeling approach was used to study the cargo status of vesicles before and after exocytosis; demonstrating a measurable loss of transmitter in individual vesicles following stimulation due to partial release. Model secretory cells were incubated with 13C-labeled l-3,4-dihydroxyphenylalanine, resulting in the loading of 13C-labeled dopamine into their vesicles. A second label, di-N-desethylamiodarone, having the stable isotope 127I, was introduced during stimulation. A significant drop in the level of 13C-labeled dopamine and a reduction in vesicle size, with an increasing level of 127I-, was observed in vesicles of stimulated cells. Colocalization of 13C and 127I- in several vesicles was observed after stimulation. Thus, chemical visualization shows transient opening of vesicles to the exterior of the cell without full release the dopamine cargo. We present a direct calculation for the fraction of neurotransmitter release from combined imaging data. The average vesicular release is 60% of the total catecholamine. An important observation is that extracellular molecules can be introduced to cells during the partial exocytotic release process. This nonendocytic transport process appears to be a general route of entry that might be exploited pharmacologically

Interpersonal Experiential Learning and Cancer Research Training Designed to Enhance the Motivation of Participating Interns Utilizing Self-Determination Theory: A Longitudinal Study with Photovoice Methodology

Historically, the underrepresentation of individuals from disadvantaged backgrounds, disabled, and diverse racial/ethnic groups in STEM fields is prevalent. Equity in stem fields allows for different perspectives and knowledge backgrounds allows for the cognitive diversity needed to tackle complex research topics. The Knight Scholars Program (KSP) aims to support underrepresented and disadvantaged high school and undergraduate students pursuing a research career by teaching them the tools they need to succeed. Spanning over three summers, KSP utilized the Self-Determination Theory (SDT) of motivation to create an inclusive learning environment and to strengthen the high schoolers\u27 motivation to pursue research careers focusing on the three physiological needs: autonomy, relatedness, and competency. Photovoices created by a cohort about their overall experiences during the two ten-week-long program segments underwent qualitative analysis to gauge the influences on scholars\u27 motivations present during their participation via qualitative analysis. These findings, discussed in the context of trainee recruitment and retention of individuals supporting diversity, equity, inclusion, and accessibility goals of programs, highlight the need for systematic support of trainees’ inherent needs for autonomy, relatedness, and competency

Visualizing B cell capture of cognate antigen from follicular dendritic cells

The prominent display of opsonized antigen by follicular dendritic cells (FDCs) has long favored the view that they serve as antigen-presenting cells for B cells. Surprisingly, however, although B cell capture of antigen from macrophages and dendritic cells has been visualized, acquisition from FDCs has not been directly observed. Using two-photon microscopy, we visualized B cell capture of cognate antigen from FDCs. B cell CXCR5 expression was required, and encounter with FDC-associated antigen could be detected for >1 wk after immunization. B cell–FDC contact times were often brief but occasionally persisted for >30 min, and B cells sometimes acquired antigen together with FDC surface proteins. These observations establish that FDCs can serve as sites of B cell antigen capture, with their prolonged display time ensuring that even rare B cells have the chance of antigen encounter, and they suggest possible information transfer from antigen-presenting cell to B cell

An Integrated Multidisciplinary Evaulation Platform and Early Experience for Precision Therapy in Resectable NSCLC

Lung cancer is the leading cause of cancer related deaths in the US, with 85% of cases classified as non-small cell lung cancer (NSCLC). 20-25% of patients with NSCLC present with resectable disease