Quantitative Intravital Calcium Imaging in Mouse Kidney.

Intracellular calcium is an important regulator of solute transport in renal epithelial cells, and disordered calcium signaling may underlie the pathogenesis of certain kidney diseases. Intravital multiphoton imaging of the kidney in transgenic mice expressing highly sensitive fluorescent reporters allows detailed study of calcium signals within different specialized segments of the renal tubule and how these are integrated with other cellular processes. Moreover, changes in activity can be observed in real time in response to physiological interventions or disease-causing insults. In this chapter, we will provide a detailed protocol for performing this powerful research technique.

Skin Permeability of Perfluorocarboxylic Acids Using Flow-Through Diffusion on Porcine Skin.

Per- and polyfluoroalkyl substances (PFAS) are found in a variety of places including cosmetics, rain jackets, dust, and water. PFAS have also been applied to occupational gear to protect against water and oils. However, PFAS have been identified as immunosuppressants and perfluorooctanoic acid (PFOA), a specific PFAS, has been identified as carcinogenic. Since there is a risk for dermal exposure to these compounds, there is a need to characterize their dermal absorption. Using in vitro flow-through diffusion, skin permeabilities were determined for 14C-labeled perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA), and perfluorobutanoic acid (PFBA) using porcine skin. Tests were conducted over 8 h with either acetone or artificial perspirant as the vehicle. PFBA was found to have greater permeability than PFHxA, likely due to having a smaller molecular weight. The dosing vehicle did not appear to impact permeability rates but impacted the disposition through the skin model. While these PFAS compounds showed a low permeability rate through the skin membranes, they can stay in the skin, acting as a reservoir.

Replacing sedentary time with sleep and physical activity: associations with physical function and wellbeing in Type 2 diabetes.

AIMS: To examine the associations of substituting sedentary behaviour (SB) for sleep, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) with physical function and wellbeing. METHODS: Cross-sectional data from 808 adults with Type 2 Diabetes Mellitus, (T2DM) were included. 24-hour behaviours were ascertained through accelerometery. Isotemporal substitution was used to estimate the theoretical substitution of SB for other 24-hour behaviours on associations with physical function and wellbeing markers. RESULTS: Reallocating 30 min of SB to sleep was beneficially associated with 1.0% (95% CI: 0.1-1.9) higher sit-to-stand-60 (STS60) and 1.2% (0.1-2.3) Duke Activity Status Index (DASI) scores, 3.6% (1.5-5.5) lower Patient Hospital Questionnaire-9 (PHQ9) and 1.9% lower (0.1-3.7) Diabetes Distress scores. Whilst substituting SB with MVPA was associated with 3.8% (2.2-5.4) higher STS60 and 3.9% (2.0-5.9) DASI scores, and 4.7% (0.3-9.0) lower PHQ9 score. Replacing SB with LPA was associated with 4.1% (1.0-7.1) lower PHQ9 score. CONCLUSION: In adults with T2DM, theoretically replacing SB with sleep and physical activity, particularly MVPA is beneficially associated with markers of physical function and wellbeing. For wellbeing, associations for sleep were comparable (depression), or greater (diabetes distress), than for MVPA.

Sleep disorders in younger and middle-older age adults with newly diagnosed type 2 diabetes mellitus: A retrospective cohort study in >1million individuals.

AIMS: To explore the 5-year incidence and relative rates of sleep disorders in younger (16-≤40 years) and middle-older (=>40 years) age adults with and without newly diagnosed type 2 diabetes. METHODS: This retrospective, observational cohort study utilised data from the US Collaborative Network within the TriNetX database. We compared 5-year cumulative incidence of sleep disorders in younger (n = 110,088) and middle-older populations (n = 1,185,961). RESULTS: The absolute risk of developing any type of sleep disorder was greater in individuals with type 2 diabetes vs. those without. Over the 5-year follow-up period, 14.2 % of younger adults and 18.5 % of middle-older age adults with newly diagnosed type 2 diabetes developed any form of sleep disorder, compared to 4.5 % and 7.9 % propensity matched individuals without diabetes. We observed a more pronounced relative rate across the observed sleep disorders in younger adults. CONCLUSIONS: The 5-year risk of sleep disorders is higher in those with newly diagnosed type 2 diabetes vs. those without. A higher absolute risk was seen in middle-older adults, but relative rates were consistently higher in younger adults with type 2 diabetes. Sleep should be regularly discussed as part of a holistic approach to diabetes care, particularly in those aged ≤40.

Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally-suppressed people with HIV.

OBJECTIVES: Virally-suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used positron emission tomography (PET) to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework. DESIGN: Cross-sectional investigation in VS-PWH (n = 25) versus HIV-uninfected individuals (n = 18) of cognitive control and declarative memory, as well as [11C]DPA-713 PET measures of TSPO within cognitive control and declarative memory regions of interest. METHODS: Group differences in [11C]DPA-713 binding (VT) in cognitive control or declarative memory regions were examined using linear mixed models. Tests of associations between factor-derived cognitive system measures and PET measures were performed, controlling for TSPO genotype. RESULTS: There were no group differences in any of the four factor-derived cognitive system measures. VS-PWH had higher log [11C]DPA-713 VT across cognitive control regions(unstandardized beta coefficient reflecting mean difference [B] = 0.23, SE = 0.11, 95% confidence interval [CI] 0.01, 0.45, P = 0.04) and declarative memory regions (B = 0.24, SE = 0.11, 95%CI 0.02, 0.45, P = 0.03). Higher log [11C]DPA-713 VT in cognitive control regions related to poorer cognitive control in each group, and to worse self-reported cognitive performance in VS-PWH. Log [11C]DPA-713 VT in each declarative memory region did not associate with measured declarative memory. CONCLUSIONS: A localized neuroimmune response marked by high TSPO in brain regions that subserve cognitive control may contribute to poorer cognitive control in VS-PWH.

Associations between Aircraft Noise, Sleep, and Sleep-Wake Cycle: Actimetric Data from the UK Biobank Cohort near Four Major Airports.

BACKGROUND: Nighttime aircraft noise may affect people's sleep, yet large-scale evidence using objective and subjective measures remains limited. OBJECTIVE: Our aim was to investigate associations between nighttime aircraft noise exposure and objectively measured sleep disturbance using a large UK cohort. METHODS: We used data from 105,770 UK Biobank cohort participants exposed and unexposed to aircraft noise who lived in 44 local authority districts near 4 international airports in England. We used a generalized linear regression model to examine cross-sectional associations between aircraft noise Lnight (23:00 hours-07:00 hours) and 7-d actimetric measures collected 2013-2015 (n=22,102). We also used Logit and generalized estimating equations models to examine associations between Lnight and self-reported sleep measures at enrollment (2006-2010) and follow-up (2012-2013). This approach allowed us to compare and contrast the results and support potential future meta-analyses on noise-related sleep disturbance. RESULTS: Cross-sectional analyses of actimetric data suggested sleep disturbance associated with Lnight, showing higher level of movements during the least active continuous 8-h time period [ß: 0.12 milligravitational units; 95% confidence interval (CI): 0.013, 0.23]. We also saw disrupted sleep-wake cycles as indicated by index scores of lower relative amplitude (ß: -0.006; 95% CI: -0.007, -0.005), poorer interdaily stability (ß: -0.010; 95% CI: -0.014, -0.006), and greater intradaily variability (ß: 0.021; 95% CI: 0.019, 0.023), comparing Lnight ≥55 dB with <45 dB. Repeated cross-sectional analyses found a 52% higher odds of more frequent daytime dozing [odds ratio (OR) =1.52; 95% CI: 1.32, 1.75] for Lnight ≥55 dB in comparison with <45 dB, whereas the likelihood for more frequent sleeplessness was more uncertain (OR=1.13; 95% CI: 0.92, 1.39). Higher effect sizes were seen in preidentified vulnerable groups, including individuals >65y of age and those with diabetes or dementia. CONCLUSION: Individuals exposed to higher levels of aircraft noise experienced objectively higher levels of sleep disturbance and changes in sleep-wake cycle. https://doi.org/10.1289/EHP14156.

Inflammatory pain in mice induces light cycle-dependent effects on sleep architecture.

As a syndrome, chronic pain comprises physical, emotional, and cognitive symptoms such as disability, negative affect, feelings of stress, and fatigue. A rodent model of long-term inflammatory pain, induced by complete Freund's adjuvant (CFA) injection, has previously been shown to cause anhedonia and dysregulated naturalistic behaviors, in a manner similar to animal models of stress. We examined whether this extended to alterations in circadian rhythms and sleep, such as those induced by chronic social defeat stress, using actigraphy and wireless EEG. CFA-induced inflammatory pain profoundly altered sleep architecture in male and female mice. Injection of the hind paw, whether with CFA or saline, reduced some measures of circadian rhythmicity such as variance, period, and amplitude. CFA increased sleep duration primarily in the dark phase, while sleep bout length was decreased in the light and increased in the dark phase. Additionally, CFA reduced wake bout length, especially during the dark phase. Increases in REM and SWS duration and bouts were most significant in the dark phase, regardless of whether CFA had been injected at its onset or 12 hours prior. Taken together, these results indicate that inflammatory pain acutely promotes but also fragments sleep.

Endoscopic Integrated Multipoint Laser System to Perform Quantitative Measurements for Anterior Skull Base Defects.

INTRODUCTION: Measurements in endoscopic sinus surgery (ESS) are usually obtained with variable accuracy. We aimed to validate endoscopic multipoint integrated laser systems (EIMLS) for use in ESS, which can acquire measurements within one-hundredth of a millimetre. METHODS: A 4.4 mm flexible endoscopic EIMLS projecting 49 laser points into the view was used to assess simulated anterior skullbase defects. Antero-posterior and lateral measurements were obtained and repeated 20 times by two surgeons. These were compared to measurements with surgical callipers. Intra and inter-observer reliability was assessed. RESULTS: Eighty measurements were obtained of simulated skullbase defects by each otolaryngology surgeon and compared to manual measurements. The mean difference shown was 0.56 cm. Bland-Altman plot shows low bias (0.044) but wide 95% limits of agreement (-1.8-1.9). CONCLUSION: EIMLS allows reliable and easy to obtain measurements within a simulated ESS environment. Translation of this technology offers promise in a future clinical setting but will require further refinement to improve accuracy.

The long-term time course of septic arthritis.

Aims: The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms. Methods: All microbiological samples from joint aspirations between March 2000 and December 2014 at our institution were reviewed in order to identify cases of culture-proven septic arthritis. Cases in children (aged < 16 years) and prosthetic joints were excluded. Data were abstracted on age at diagnosis, sex, joint affected (hip or knee), type of organisms isolated, cause of septic arthritis, comorbidities within the Charlson Comorbidity Index (CCI), details of treatment, and outcome. Results: A total of 142 patients were confirmed to have had an episode of septic arthritis in a native hip (n = 17) or knee joint (n = 125). S. aureus accounted for 57.7% of all hip and knee joint infections. There were 13 inpatient deaths attributed to septic arthritis. The median age of the patients who died was 77.5 (46.9 to 92.2) and their median age-adjusted CCI was 8 (6 to 12). A failure of the joint occurred in 26 knees (21%) and nine hips (53%). Of the knee joints infected by S. aureus (n = 71), 23 knees (32%) went into failure of joint, whereas of those infected by other organisms (n = 54), only three knees (6%) failed. Conclusion: Based on our study findings, hip and knee septic arthritis long-term outcomes were substantially worse than their immediate outcome suggested. Failure of knee joint is 6.1 times more likely to occur in those infected with S. aureus.

Is Competency-Based Medical Education being implemented as intended? Early lessons learned from Physical Medicine and Rehabilitation.

Background: As competency-based medical education (CBME) curricula are introduced in residency programs across Canada, systematic evaluation efforts are needed to ensure fidelity of implementation. This study evaluated early outcomes of CBME implementation in one Canadian Physical Medicine and Rehabilitation program that was an early adopter of CBME, with an aim to inform continuous quality improvement initiatives and CBME implementation nationwide. Methods: Using Rapid Evaluation methodology, informed by the CBME Core Components Framework, the intended outcomes of CBME were compared to actual outcomes. Results: Results suggested that a culture of feedback and coaching already existed in this program prior to CBME implementation, yet faculty felt that CBME added a framework to support feedback. The small program size was valuable in fostering strong relationships and individualized learning. However, participants expressed concerns about CBME fostering a reductionist approach to the development of competence. Challenges existed with direct observation, clear expectations for off-service training experiences, and tracking trainee progress. There was trepidation surrounding national curricular change, yet the institution-wide approach to CBME implementation created shared experiences and a community of practice. Conclusions: Program evaluation can help understand gaps between planned versus enacted implementation of CBME, and foster adaptations to improve the fidelity of implementation.

Contexte: À mesure que les programmes d'approche par compétences (APC) en formation médicale sont introduits dans les programmes de résidence au Canada, des efforts d'évaluation systématiques sont nécessaires pour assurer la fidélité de la mise en œuvre. Cette étude a évalué les premiers résultats de la mise en œuvre de l'APC en formation médicale dans un programme canadien de médecine physique et réadaptation, qui a été un des premiers à adopter l'APC, dans le but d'orienter les initiatives d'amélioration continue de la qualité et de la mise en œuvre de l'APC à l'échelle nationale. Méthodes: En utilisant une méthodologie d'évaluation rapide, fondée sur le cadre des composantes de base de l'APC en formation médicale, les résultats escomptés de l'APC ont été comparés aux résultats réels. Résultats: Les résultats suggèrent qu'une culture de la rétroaction et de l'encadrement existait déjà dans ce programme avant la mise en œuvre de l'APC, mais le corps professoral a estimé que l'APC en formation médicale a ajouté un cadre pour soutenir cette rétroaction. La petite taille du programme a permis de favoriser des relations solides et un apprentissage individualisé. Cependant, les participants ont exprimé des inquiétudes quant au fait que l'APC favorise une approche réductionniste du développement des compétences. L'observation directe, les attentes claires en matière d'expériences de formation hors de l'environnement clinique et le suivi des progrès des résidents posent problème. Le changement de programme national a suscité des inquiétudes, mais l'approche institutionnelle de la mise en œuvre de l'APC a permis de partager des expériences et de créer une communauté de pratique. Conclusions: L'évaluation des programmes peut aider à comprendre les écarts entre la mise en œuvre planifiée et effective de l'APC en formation médicale, et de favoriser les adaptations pour améliorer le respect des conditions de mise en œuvre.

A useful cognitive motor dual task paradigm in prodromal and manifest Huntington's disease.

INTRODUCTION: Individuals with Huntington's disease (HD) experience increased difficulty with balance throughout disease progression. Adding a simultaneous cognitive task to a balance assessment, referred to as a dual task (DT) paradigm, may have a deleterious effect on balance, which can be expressed in terms of a Dual Task Cost (DTC), relative to a single task (ST) condition. The aim of this study is to explore whether a cognitive-motor DT paradigm uncovers balance deficits in prodromal (Pro-HD) and manifest HD, compared to healthy adults (HA). METHODS: Balance under ST and DT conditions was examined using the BTracks Balance Plate and Balance software in 30 individuals with HD, 17 individuals with Pro-HD, and 20 HA. During the DT condition, participants were simultaneously administered a version of the Paced Auditory Serial Addition Test (PASAT). DTC is calculated as the relative ratio of ST to DT, controlling for ST performance: DTC= (ST - DT)/ST x100. RESULTS: The HA group performed significantly better than the HD group on both the ST and DT conditions (p < 0.01), while balance scores between the HA and the Pro-HD groups were not significantly different. The DTC scores, however, were significantly better in the HA compared to both the HD (p < 0.001) and Pro-HD (p < 0.05) groups. CONCLUSION: Our findings indicate that the addition of a cognitive task interferes with participant's balance, reflecting real-life performance, and may have additional value for estimating transition to manifest disease, appraising fall risk, or serving as a valid outcome measure in observational and interventional trials in HD.

A radioligand for in vitro autoradiography of CSF1R in post-mortem CNS tissues.

BACKGROUND: Reactive microglia and recruited peripheral macrophages contribute to the pathogenesis of Alzheimer's dementia (AD). Monocytes, macrophages and microglia all express the marker colony-stimulating factor 1 receptor (CSF1R). 4-Cyano-N-(4-(4-methylpiperazin-1-yl)-2-(4-methylpiperidin-1-yl)phenyl)-1H-pyrrole-2-carboxamide (1) is a high-affinity antagonist for CSF1R. We report the radiosynthesis of both [3H]1 and [11C]1. The PET imaging properties of [11C]1 in mice and baboon were investigated. [3H]1 was studied in Bmax measurement in post-mortem autoradiography in the frontal cortex, inferior parietal cortex and hippocampus from donors diagnosed with AD and age-matched controls. In vitro binding affinity of 1 was measured commercially. Nor-methyl-1 precursor was radiolabeled with [11C]iodomethane or [3H]iodomethane to produce [11C]1 and [3H]1, respectively. Ex vivo brain biodistribution of [11C]1 was compared in normal mice versus lipopolysaccharide-administered (LPS) murine model of neuroinflammation. Dynamic PET imaging was performed in a healthy male Papio anubis baboon. Post-mortem autoradiography with [3H]1 was performed in frozen sections using a standard saturation binding technique. RESULTS: Compound 1 exhibits a high in vitro CSF1R binding affinity (0.59 nM). [11C]1 was synthesized with high yield. [3H]1 was synthesized similarly (commercially). Biodistribution of [11C]1 in healthy mice demonstrated moderate brain uptake. In LPS-treated mice the brain uptake of [11C]1 was ~ 50% specific for CSF1R. PET/CT [11C]1 study in baboon revealed low brain uptake (0.36 SUV) of [11C]1. Autoradiography with [3H]1 gave significantly elevated Bmax values in AD frontal cortex versus control (47.78 ± 26.80 fmol/mg vs. 12.80 ± 5.30 fmol/mg, respectively, P = 0.023) and elevated, but not significantly different binding in AD hippocampus grey matter and inferior parietal cortex (IPC) white matter. CONCLUSIONS: Compound 1 exhibits a high in vitro CSF1R binding affinity. [11C]1 specifically labels CSF1R in the mouse neuroinflammation, but lacks the ability to efficiently cross the blood-brain barrier in baboon PET. [3H]1 specifically labels CSF1R in post-mortem human brain. The binding of [3H]1 is significantly higher in the post-mortem frontal cortex of AD versus control subjects.

Mental Health Evacuation Rate in USCENTCOM.

BACKGROUND: Mental health diagnosis requiring further treatment is one of the top reasons for medical evacuation in the U.S. Central Command (USCENTCOM) area of responsibility (AOR) as of 2022. This study establishes a baseline in which the effectiveness of medical interventions can be measured to determine if they have an impact on the rate of evacuation out of USCENTCOM. MATERIALS AND METHODS: The study period was January 1, 2017 to December 31, 2021. Individual evacuation data including date of initial movement and necessary specialty care requirements originating from the USCENTCOM AOR were acquired via U.S. Transportation Command's Regulating and Command & Control Evacuation System. The base evacuation rate was calculated for each month, and evacuation rates were analyzed for variations. RESULTS: For the entire study period, the mean monthly evacuation rate was 0.44 evacuations per 1,000 people in the AOR (95% CI, 0.41-0.47). There was no statistically significant difference between any monthly evacuation rate (P = .505). There is a statistically significant difference in the mean evacuation rates for calendar years (P = .003). The highest evacuation rate occurred in 2021. CONCLUSIONS: The study establishes a benchmark mental health evacuation rate. This rate will be useful for assessing mental health evacuation reduction initiatives in the USCENTCOM AOR.

Combatant Command Medical Entry Standards.

INTRODUCTION: The medical entry standards for the United States Central Command (USCENTCOM) restrict individuals with various medical conditions from entering the deployed environment. The impact of this program is unknown. MATERIALS AND METHODS: The total number of army personnel deployed to USCENTCOM, the number of individuals with a medical entry waiver adjudicated by United States Army Central (USARCENT), and the evacuation number for each population were compared for calendar year 2023 (CY2023). RESULTS: A total estimated population of 20,519 U.S. Army personnel were deployed to USCENTCOM. A population of 1,918 received a medical entry waiver due to a disqualifying medical condition. The evacuation rate for the general population was 2.4% compared to the 1.4% evacuation rate of the population with a medical entry waiver (P = .0027). CONCLUSION: The medical entry standards, as written and adjudicated in 2023, resulted in a relatively reduced evacuation rate for individuals with otherwise prohibited medical conditions compared to the general deployed population.

Capturing How the Accelerometer Measured Physical Activity Profile Differs in People with Diabetic Foot Ulceration.

Diabetic Foot Ulcers (DFUs) are a major complication of diabetes, with treatment requiring offloading. This study aimed to capture how the accelerometer-assessed physical activity profile differs in those with DFUs compared to those with diabetes but without ulceration (non-DFU). Participants were requested to wear an accelerometer on their non-dominant wrist for up to 8days. Physical activity outcomes included average acceleration (volume), intensity gradient (intensity distribution), the intensity of the most active sustained (continuous) 5-120 min of activity (MXCONT), and accumulated 5-120 min of activity (MXACC). A total of 595 participants (non-DFU = 561, DFU = 34) were included in the analysis. Average acceleration was lower in DFU participants compared to non-DFU participants (21.9 mg [95%CI:21.2, 22.7] vs. 16.9 mg [15.3, 18.8], p < 0.001). DFU participants also had a lower intensity gradient, indicating proportionally less time spent in higher-intensity activities. The relative difference between DFU and non-DFU participants was greater for sustained activity (MXCONT) than for accumulated (MXACC) activity. In conclusion, physical activity, particularly the intensity of sustained activity, is lower in those with DFUs compared to non-DFUs. This highlights the need for safe, offloaded modes of activity that contribute to an active lifestyle for people with DFUs.

Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics.

Background and aims: The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalised treatments. Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus (HBV) and HDV or HIV co-infection. Method: The NanoString GeoMx digital spatial profiling platform was employed to assess expression of HBV surface antigen and CD45 in formalin-fixed paraffin-embedded (FFPE) biopsies from three treatment-naïve patients with chronic HBV and HDV or HIV co-infection. The GeoMx Human Whole Transcriptome Atlas assay quantified the expression of genes enriched in specific regions of interest (ROIs). Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas. A weighted gene correlation network analysis evaluated transcriptomic signatures across sampled regions. Results: Spatially discrete transcriptomic signatures and distinct biological pathways were associated with HBV infection/disease status and immune responses. Shared features including 'cytotoxicity' and 'B cell receptor signalling' were consistent across patients, suggesting common elements alongside individual traits. HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment, whereas HIV/HBV co-infection featured genes related to interferon response regulation. Varied cellular characteristics and immune cell populations, with an abundance of γδT cells in the HDV/HBV sample, were observed within analysed regions. Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression. Conclusion: This proof-of-principle study shows the value of this platform in investigating the complex immune landscape, highlighting relevant host pathways to disease pathogenesis.

Competency based medical education implementation at the institutional level: A cross-discipline comparative program evaluation.

INTRODUCTION: As an early adopter of competency-based medical education (CBME) our postgraduate institution was uniquely positioned to analyze implementation experience data across programs, while keeping institutional factors constant. We described participants' experiences related to CBME implementation across programs derived from early program evaluation efforts within our setting. METHODS: This evaluation focused on eight residency programs at a medium-sized academic institution in Canada. Participants (n = 175) included program leaders, faculty, and residents. The study consisted of 3 phases: (1) describing intended implementation; (2) documenting enacted implementation; and (3) comparing intended with enacted implementation to inform adaptations. Each program's findings were summarized in technical reports which were then analyzed thematically. Cross program data were organized by themes. RESULTS: Six themes were identified. All groups emphasized the need for ongoing refinement of CBME resulting from shared tensions such as increased assessment burden. However, there were some disparate CBME-related experiences between programs such as the experience with entrustable professional activities, the interpretation of retrospective entrustment anchors, and quality of feedback. CONCLUSION: We detected several cross-program successes and important challenges related to CBME. Our experience can inform other programs engaging in implementation and evaluation of CBME.

Superior Tumor Cell Uptake by Mono- and Tri-Nuclear Rhodamine-Gadolinium(III) Agents.

The synthesis and characterization of a novel trinuclear rhodamine-Gd(III) complex, along with two analogous mononuclear rhodamine-Gd(III) complexes, are reported. All complexes displayed good selectivity in a human glioma cell line (T98G) when compared to a glial cell line (SVG p12), with low cytotoxicities. Superior tumor cell uptake for these Gd(III) complexes was observed at lower incubation concentrations compared to previously-reported delocalized lipophilic cations such as a rhodamine-lanthanoid(III) probe and Gd(III)-arylphosphonium complexes, with ca. 150 % and 250 % increases in Gd uptake, respectively.

Chondroprotection of articular cartilage integrity: Utilizing ultrasonic scalpel and hyperosmolar irrigation solution during cutting.

Objectives: Ultrasonic (US) cutting of cartilage in orthopaedic surgery has received little attention despite its potential to reduce chondrocyte death which could enhance cartilage repair. We aimed to investigate whether an ultrasonically-vibrating scalpel to cut human articular cartilage could reduce chondrocyte death, and to determine if hyper-osmolarity could provide chondroprotection during the procedure. Methods: A scalpel (no. 15) was mounted on an ultrasonic transducer to resonate at 35 â€‹kHz with 30 â€‹µm vibrational displacement. Thirty-six fresh human femoral cartilage samples were divided into four groups based on ultrasonic activation (US or non-US) and saline osmolarity (300 or 600 mOsm/L). Cell viability was assessed using a live/dead cell assay and analysed quantitatively by confocal microscopy. Histology illustrated tissue surface changes at the cut site. Results: The overall chondrocyte death percentage at both the US and non-US cut sites showed comparable results (p â€‹> â€‹0.05) in both osmolarities. However, the zone of chondrocyte death was reduced by 31 â€‹± â€‹5% and 36 â€‹± â€‹6%, respectively, when comparing US cutting at 300 mOsm/L and 600 mOsm/L to the control group (non-US cutting; 300 mOsm/L) (p â€‹< â€‹0.05). The width of the cut was consistent at both sites, regardless of the method of cutting. Conclusion: Cutting human cartilage with US in the presence of 300 or 600 mOsm/L media was chondroprotective compared to normal (non-US) scalpel cutting in 300 mOsm/L medium. These results suggest chondroprotection can be achieved while cutting using a US scalpel and raised osmolarity, potentially improving cartilage regeneration and repair following injury.