Characterization of spatiotemporal and kinetic gait variables in dogs with hindlimb ataxia and bilateral hindlimb lameness.

BACKGROUND: Discriminating the underlying cause of gait abnormalities can be challenging in a clinical setting, especially in the presence of bilateral disease. Pressure-sensitive walkways (PSWs) have been utilized to characterize the gait of dogs with various neurologic or orthopaedic conditions. The potential use of the PSW includes the discrimination of conditions that can be similar in clinical presentation, such as bilateral hindlimb lameness and hindlimb ataxia. The primary aim of this study was to describe the spatial, temporal, and kinetic gait parameters of dogs with hindlimb ataxia or bilateral hindlimb lameness and compare them to those of normal dogs. Forty-six dogs were prospectively recruited. The normal group included 20 dogs with normal neurologic and orthopaedic exams. The orthopaedic group included 15 dogs with bilateral hindlimb orthopaedic diseases with weight-bearing hindlimb lameness and normal neurologic exams. The neurologic group included 11 dogs with ambulatory paraparesis and normal orthopaedic exams. Each dog was walked across the PSW, and at least 3 valid trials were collected. The stride time, stance time, swing time, stride length, gait velocity, peak vertical force (PVF), vertical impulse (VI), and limb symmetry were recorded. The mean values of all parameters from the valid trials were calculated and used for data analysis. The outcomes were compared among all groups. RESULTS: Compared with the normal group, the orthopaedic group had a significantly greater percent body weight distribution (%BWD) and vertical impulse distribution (VID) in the forelimbs. When comparing the spatiotemporal parameters, the neurologic group showed an increase in forelimb stance time compared to that of the normal group. Compared with that in the normal group, the stride velocity in the forelimbs in the orthopaedic group was greater. There were no significant differences in the kinetic parameters between the neurologic group and the normal group, nor in stride time or stride length among the groups. CONCLUSION: The gait parameters obtained by PSW demonstrated that the orthopaedic and neurologic groups may have different compensatory mechanisms for their gait deficiencies. These parameters can potentially be used to construct a predictive model to evaluate PSW as a diagnostic tool in future studies.

Eosinophils respond to, but are not essential for control of an acute Salmonella enterica serovar Typhimurium infection in mice.

Eosinophils are a highly abundant cell type in the gastrointestinal tract during homeostatic conditions, where they have recently been reported to take on an activated phenotype following colonization by the bacterial microbiota. To date, there have been few studies investigating whether eosinophils respond to infection with enteric bacterial pathogens and/or investigating the requirements for eosinophils for effective bacterial pathogen control. In this study, we investigated the response of eosinophils to an acute enteric infection of mice with the bacterial pathogen Salmonella enterica serovar Typhimurium. We also assessed whether eosinophil deficiency impacted Salmonella burdens in the intestinal tract or impacted the systemic dissemination of Salmonella following an oral infection of littermate wild-type BALB/cJ and eosinophil-deficient ΔdblGATA BALB/cJ mice. We found comparable Salmonella burdens in the intestinal tract of wild-type and eosinophil-deficient mice and no significant differences in the levels of Salmonella disseminating to systemic organs within 3 days of infection. Despite our evidence suggesting that eosinophils are not an essential cell type for controlling bacterial burdens in this acute infection setting, we found higher levels of eosinophils in gut-draining lymph nodes following infection, indicating that eosinophils do respond to Salmonella infection. Our data contribute to the growing evidence that eosinophils are responsive to bacterial stimuli, yet the influence of and requirements for eosinophils during bacterial infection appear to be highly context-dependent.

From individual to interprofessional: characteristics of assessment tasks to assess interprofessional collaboration in healthcare education.

To develop independent healthcare professionals able to collaborate in interprofessional teams, health professions education aims to support students in transitioning from an individual perspective to interprofessional collaboration. The five elements that yield the conditions for effective interprofessional collaboration are: (1) positive interdependence, (2) individual accountability, (3) promotive interaction, (4) interpersonal skills, and (5) reflection on team processes. The aim of the current study is to gain insights into how to design tasks to assess a student team as a whole on their interprofessional collaboration. This was a pilot study using a qualitative design to evaluate an interprofessional assessment task. Four interprofessional student teams, comprising physiotherapy, occupational therapy, arts therapy and nursing students (N = 13), completed this task and five assessors used a rubric to assess video recordings of the teams' task completion, and then participated in a group interview. The completed rubrics and the interview transcript were analyzed using content analysis. Findings showed that the combination of individual preparation, an interprofessional team meeting resulting in care agreements and team reflection was a strength of the assessment task, enabling the task to elicit sufficient promotive interaction between students. Areas for improvement of the assessment task were however, due to a lack of interdependence, the care agreements which now proved to be the sum of students' intraprofessional ideas rather than an interprofessional integration of agreements. Additionally, assessors suggested that a series of varying assessment tasks is required to draw conclusions about students' interprofessional competence.

Rare presence and function of neuroendocrine cells in the nasal mucosa.

There is growing evidence that neurogenic inflammation contributes to the pathophysiology of upper airway diseases, with nasal hyperreactivity (NHR) being a key symptom. The rare neuroendocrine cells (NECs) in the epithelium have been linked to the pathophysiology of bronchial and intestinal hyperreactivity, however their presence in the nasal mucosa and their potential role in NHR remains unclear. Therefore, we studied the presence of NECs in the nasal epithelium of controls, allergic rhinitis patients and chronic rhinosinusitis with nasal polyps patients, and their link to NHR. The expression of typical NECs markers, CHGA, ASCL1 and CGRP, were evaluated on gene and protein level in human samples using real-time quantitative PCR (RT-qPCR), western blot, immunohistochemistry fluorescence staining, RNA scope assay, flow cytometry and single cell RNA-sequencing. Furthermore, the change in peak nasal inspiratory flow after cold dry air provocation and visual analogue scale scores were used to evaluate NHR or disease severity, respectively. Limited gene expression of the NECs markers CHGA and ASCL1 was measured in patients with upper airway diseases and controls. Gene expression of these markers did not correlate with NHR severity nor disease severity. In vitro, CHGA and ASCL1 expression was also evaluated in primary nasal epithelial cell cultures from patients with upper airway disease and controls using RT-qPCR and western blot. Both on gene and protein level only limited CHGA and ASCL1 expression was found. Additionally, NECs were studied in nasal biopsies of patients with upper airway diseases and controls using immunohistochemistry fluorescence staining, RNA scope and flow cytometry. Unlike in ileum samples, CHGA could not be detected in nasal biopsies of patients with upper airway diseases and control subjects. Lastly, single cell RNA-sequencing of upper airway tissue could not identify a NEC cluster. In summary, in contrast to the bronchi and gut, there is only limited evidence for the presence of NECs in the nasal mucosa, and without correlation with NHR, thereby questioning the relevance of NECs in upper airway pathology.

Factors Influencing Participation and Engagement in a Teen Safe Driving Intervention: A Qualitative Study.

(1) Background: Few teen driving safety programs focus on increasing parental engagement with high-risk teen drivers, specifically those with a traffic violation. This study explored parents'/guardians' ('parents') experiences with a teen driving safety program, ProjectDRIVE, including facilitators and barriers to program engagement. (2) Methods: We conducted virtual, semi-structured interviews with parents who completed ProjectDRIVE, which included in-vehicle driving feedback technology and individualized virtual training with parents on effective parent-teen communication. (3) Results: Twenty interviews (with 17 females and three males) were transcribed verbatim and independently coded by three coders using systematic, open, and focused coding. Three major themes were identified: factors influencing a parent's initial decision to participate, factors influencing continued engagement, and perceived benefits of participation. The decision to participate was influenced by these subthemes: parental motivation to help their teen, perceived program usefulness, program endorsement, program incentives, parents' busy schedules, and lack of access to a car/internet. Subthemes impacting continued engagement included enhanced communication skills, teen willingness to engage, strong parental engagement, and teens' other priorities. Perceived benefits included greater self-efficacy in communication, improved communication patterns and frequency, and enhanced parent-teen relationships. (4) Conclusions: These findings may set the foundation for developing and implementing future court-ordered parent-based teen safe driving programs for teens with traffic citations.

A Rare Presentation of Cholangitis Associated With Invasive Streptococcus Pyogenes.

Streptococcus pyogenes (S. pyogenes) is a gram-positive, facultative anaerobic bacterium that appears as cocci in chains and commonly causes skin infections and pharyngitis. Here, we present a very uncommon case of cholangitis associated with invasive S. pyogenes infection in a 34-year-old man with metastatic pancreatic adenocarcinoma who presented with fever, right upper quadrant pain, jaundice, altered mental status, and hypotension. The patient underwent a percutaneous transhepatic cholangiogram, showing moderate dilatation of intrahepatic biliary ducts with obstruction of the proximal common bile duct, and an internal/external biliary drain was placed to allow for the flow of bile. Blood cultures grew S. pyogenes. Biliary fluid culture obtained at the time of drain placement grew S. pyogenes, lactobacilli, and saccharomyces. The patient was treated with ampicillin-sulbactam and fluconazole. While the patient recovered from his sepsis, he died within weeks of diagnosis due to complications of metastatic disease.

Combined Exercise and Diet Induce Airway Hyperreactivity While Reducing Liver Steatosis in Mice with Diet-Induced Obesity.

BACKGROUND: Obesity is a multi-organ system disease, which is associated with, e.g., a higher prevalence of non-alcoholic fatty liver disease (NAFLD) and asthma. Little is known regarding the effect of obesity-related parameters (including liver integrity) and the respiratory phenotype after a combination of physical activity and diet. METHODS: Thirty-two C57BL/6 mice were, after 27 weeks of a high fat diet (HFD), randomly assigned to two dietary interventions for three weeks: a HFD or a normal chow diet (NCD). In both dietary groups, half of the animals were subjected to a sub-maximal exercise protocol. Lung function, lung inflammation, liver histology, and metabolic profile were determined. RESULTS: Mice with obesity did not show airway hyperreactivity after methacholine provocation. Sub-maximal exercise with diet (NCD/E) induced a significant reduction in forced expiratory volume in 0.1 s after methacholine provocation. NCD/E had significantly more neutrophils and inflammation (IFN-γ, TNF-α, IL-4, and IL-17F) in bronchoalveolar lavage compared to non-exercising mice on a HFD (HFD/NE). However, more epithelial injury (serum surfactant protein D and IL-33) was seen in HFD/NE. Additionally, hepatic steatosis and fibrosis were reduced by combined diet and sub-maximal exercise. CONCLUSIONS: Combining sub-maximal exercise with diet induced airway hyperreactivity and pulmonary inflammation, while body weight, hepatic steatosis, and fibrosis improved.

Rabies Vaccine for Prophylaxis and Treatment of Rabies: A Narrative Review.

Rabies, a millennia-old viral infection transmitted through animal bites, poses a lethal threat to humans, with a historic fatality rate of 100% if left untreated. Louis Pasteur's introduction of the rabies vaccine in 1885 marked a turning point in the battle against rabies, preventing numerous cases. The purpose of this paper is to review the historical development, current challenges, and future prospects of rabies vaccination and treatment, with emphasis on the importance of continued research and collaborative efforts in the quest to eradicate this deadly infection. Historical vaccine development progressed from inactivated to live-attenuated forms, with modern recombinant techniques showing promise. The preventive measures at present primarily involve vaccination, but challenges persist, such as differing safety profiles and immunogenicity among vaccine types. Pre-exposure prophylaxis with a three-dose vaccine series is crucial, especially in high-risk scenarios. Post-exposure prophylaxis combines human rabies immunoglobulin and inactivated rabies virus vaccine. The quest for the next generation of vaccines explores genetically modified and viral vector-based approaches; emerging treatments include gene therapy, virus-like particles, and monoclonal antibodies, offering hope for improved outcomes. Economic barriers to post-exposure prophylaxis, limited education, and awareness challenge rabies control. Cost-effective solutions and comprehensive awareness campaigns are vital for the successful eradication of rabies. More research and collaborative endeavors remain pivotal in the ongoing journey to eradicate rabies, one of the deadliest infectious diseases known to humans, if not met with prophylactic measures.

A Spectroscopic and Computational Evaluation of Uranyl Oxo Engagement with Transition Metal Cations.

We report the synthesis and characterization of five novel Cd2+/UO22+ heterometallic complexes that feature Cd-oxo distances ranging from 78 to 171% of the sum of the van der Waals radii for these atoms. This work marks an extension of our previously reported Pb2+/UO22+ and Ag+/UO22+ complexes, yet with much more pronounced structural and spectroscopic effects resulting from Cd-oxo interactions. We observe a major shift in the U═O symmetric stretch and significant uranyl bond length asymmetry. The ρbcp values calculated using Quantum Theory of Atoms in Molecules (QTAIM) support the asymmetry displayed in the structural data and indicate a decrease in covalent character in U═O bonds with close Cd-oxo contacts, more so than in related compounds containing Pb2+ and Ag+. Second-order perturbation theory (SOPT) analysis reveals that O spx → Cd s is the most significant orbital overlap and U═O bonding and antibonding orbitals also contribute to the interaction (U═O σ/π → Cd d and Cd s → U═O σ/π*). The overall stabilization energies for these interactions were lower than those in previously reported Pb2+ cations, yet larger than related Ag+ compounds. Analysis of the equatorial coordination sphere of the Cd2+/UO22+ compounds (along with Pb2+/UO22+ complexes) reveals that 7-coordinate uranium favors closer, stronger Mn+-oxo contacts. These results indicate that U═O bond strength tuning is possible with judicious choice of metal cations for oxo interactions and equatorial ligand coordination.

Double Digest: A Rare Case Report of Amphicrine Gastric Carcinoma Co-occurring With Papillary Thyroid Carcinoma.

With improved cancer treatments and patient lifespans, the incidence of a second cancer diagnosis in a person's lifetime is increasing. While dual cancer diagnoses during one's lifetime are becoming more common, diagnosis with two separate cancers simultaneously is less so. In this report we present a 55-year-old obese woman with a history of chronic lymphocytic thyroiditis and a non-specific family history of thyroid cancer who received synchronous diagnoses of amphicrine carcinoma (AC) and papillary thyroid carcinoma (PTC) during work-up for bariatric surgery. AC is a very rare form of gastric cancer characterized by the presence of both endocrine and epithelial cell components within the same cell with only a few case reports in the literature. This is the first case report to present the co-occurrence of AC with PTC.

The nasal basal cell population shifts toward a diseased phenotype with impaired barrier formation capacity in allergic rhinitis.

BACKGROUND: The integrity of the airway epithelium is guarded by the airway basal cells that serve as progenitor cells and restore wounds in case of injury. Basal cells are a heterogenous population, and specific changes in their behavior are associated with chronic barrier disruption-mechanisms that have not been studied in detail in allergic rhinitis (AR). OBJECTIVE: We aimed to study basal cell subtypes in AR and healthy controls. METHODS: Single-cell RNA sequencing (scRNA-Seq) of the nasal epithelium was performed on nonallergic and house dust mite-allergic AR patients to reveal basal cell diversity and to identify allergy-related alterations. Flow cytometry, immunofluorescence staining, and in vitro experiments using primary basal cells were performed to confirm phenotypic findings at the protein level and functionally. RESULTS: The scRNA-Seq, flow cytometry, and immunofluorescence staining revealed that basal cells are abundantly and heterogeneously present in the nasal epithelium, suggesting specialized subtypes. The total basal cell fraction within the epithelium in AR is increased compared to controls. scRNA-Seq demonstrated that potentially beneficial basal cells are missing in AR epithelium, while an activated population of allergy-associated basal cells is more dominantly present. Furthermore, our in vitro proliferation, wound healing assay and air-liquid interface cultures show that AR-associated basal cells have altered progenitor capacity compared to nonallergic basal cells. CONCLUSIONS: The nasal basal cell population is abundant and diverse, and it shifts toward a diseased state in AR. The absence of potentially protective subtypes and the rise of a proinflammatory population suggest that basal cells are important players in maintaining epithelial barrier defects in AR.

Validity, reliability and responsiveness of a French translation of the Western Ontario Osteoarthritis of the Shoulder index (WOOS).

INTRODUCTION: While several general questionnaires can be used to evaluate shoulder conditions, very few tools specifically evaluate the impact of shoulder osteoarthritis. The Western Ontario Osteoarthritis of the Shoulder index (WOOS) is a patient-reported outcome measure with excellent psychometric properties intended for patients suffering from shoulder osteoarthritis. Unfortunately, there is no validated French version of this questionnaire. OBJECTIVE: Produce a validated French version of the WOOS that is suitable for the Francophone populations of Europe and North America. MATERIAL AND METHODS: A validated protocol was used to create a French version of the WOOS (WOOS-Fr). Included were patients whose first language was French, who could read French and who had shoulder osteoarthritis destined for treatment (surgical treatment=arthroplasty). The WOOS-Fr was compared to the Disability of the Arm, Shoulder and Hand-French translation (F-QuickDASH-D/S) to assess its validity. Reliability and responsiveness were also analyzed. RESULTS: A French version of the WOOS (WOOS-Fr) was accepted by a multinational committee. The WOOS-Fr was validated in 71 French-speaking subjects. A strong positive correlation was found between the WOOS-Fr and the F-QuickDASH-D/S during the initial evaluation. The intra-class correlation (ICC) of the total WOOS-Fr score indicated good reliability between the initial WOOS and the 1-week WOOS (ICC: 0.84; 95% CI: [0.767; 0.896]; p-value: <0.001) in 57 patients. The responsiveness between the initial WOOS-Fr and at 1 year postoperative was high in the 36 operated patients (standardized mean response of 1.95). DISCUSSION: A French translation of the WOOS questionnaire was created and validated for use in French-speaking populations. This questionnaire will make it easier to evaluate the psychometric results of patients with shoulder osteoarthritis in Francophone countries. LEVEL OF EVIDENCE: III; multicenter cohort study.

Tumor Necrosis Factor and Interleukin Modulators for Pathologic Pain States: A Narrative Review.

Chronic pain, a complex and debilitating condition, involves intricate interactions between central and peripheral inflammatory processes. Cytokines, specifically tumor necrosis factor (TNF) and interleukins (IL), are key mediators in the initiation and maintenance of chronic pain states. Sensory neurons expressing receptors for cytokines like TNF, IL-1, and IL-6 are implicated in peripheral sensitization, contributing to increased signaling of painful sensations. The potential of targeting TNF and IL for therapeutic intervention in chronic pain states is the focus of this review, with preclinical and clinical evidence supporting the use of TNF and IL modulators for pain management. The physiological and pathological roles of TNF in neuropathic pain is complex. Experimental evidence highlights the effectiveness of TNF modulation in mitigating pain symptoms in animal models and displays promising outcomes of clinical trials with TNF inhibitors, such as infliximab and etanercept. ILs, a diverse group of cytokines, including IL-1, IL-6, and IL-17, are discussed for their contributions to chronic pain through inflammation and peripheral sensitization. Specific IL modulators, such as secukinumab and tocilizumab, have shown potential in managing chronic neuropathic pain, as demonstrated in various studies and clinical trials. The pharmacokinetics, safety profiles, and challenges associated with TNF and IL modulators highlight the need for cautious medication monitoring in clinical practice. Comparative evaluations have revealed distinct efficacy and safety profiles among different cytokine modulators, emphasizing the need for personalized approaches based on the specific underlying causes of pain. Further research is necessary to elucidate the intricate mechanisms by which cytokines contribute to chronic pain, as well as to understand why they may affect pain differently in various contexts. Additionally, long-term safety profiles of cytokine modulators require more thorough investigation. This continued exploration holds the promise of enhancing our comprehension of cytokine modulation in chronic pain and shaping more potent therapeutic strategies for the future.

A 10-day theta burst stimulation intervention facilitates the clinical rehabilitation of patients following an isolated limb fracture: A longitudinal SHAM-controlled pilot study.

OBJECTIVE: We investigated if theta burst stimulation (TBS) could enhance recovery by reducing key symptoms when implemented acutely post-fracture in participants with an isolated upper limb fracture (IULF). METHODS/DESIGN: This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous TBS protocol. Two main groups were included: I) participants with IULF receiving active TBS; and II) patients with IULF receiving SHAM/placebo. Another group (III) of healthy individuals were the reference group. Disability and pain intensity were collected through questionnaires (DASH & NRA) at three timepoints (baseline; 72 h post-intervention & 3 months post-injury). Group III completed the baseline assessment. RESULTS: 79 participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between Intervention and Time approached significance (F = 2.33; p = 0.11), whereas it was significant for pain (F = 3.42; p = 0.04). At 3 months post-injury, the ACTIVE group reported reduced disability (F = 4.71; p = 0.04) and pain (F = 5.84; p = 0.02) at three months post-injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls. CONCLUSIONS: In IULF patients, a 10-day TBS intervention implemented acutely post-trauma had beneficial effects on symptoms of functional recovery and pain at 3 months post-trauma.

A framework for longitudinal latent factor modelling of treatment response in clinical trials with applications to Psoriatic Arthritis and Rheumatoid Arthritis.

OBJECTIVE: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting. Therefore, to complement existing approaches, we set out here to design a longitudinal multivariate analytical framework that accepts as input an entire clinical trial database, comprising all measurements, patients, and time points across multiple trials. METHODS: Our framework composes probabilistic principal component analysis with a longitudinal linear mixed effects model, thereby enabling clinical interpretation of multivariate results, while handling data missing at random, and incorporating covariates and covariance structure in a computationally efficient and principled way. RESULTS: We illustrate our approach by applying it to four phase III clinical trials of secukinumab in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). We identify three clinically plausible latent factors that collectively explain 74.5% of empirical variation in the longitudinal patient database. We estimate longitudinal trajectories of these factors, thereby enabling joint characterisation of disease progression and drug effect. We perform benchmarking experiments demonstrating our method's competitive performance at estimating average treatment effects compared to existing statistical and machine learning methods, and showing that our modular approach leads to relatively computationally efficient model fitting. CONCLUSION: Our multivariate longitudinal framework has the potential to illuminate the properties of existing composite endpoint methods, and to enable the development of novel clinical endpoints that provide enhanced and complementary perspectives on treatment response.

Respiration and Heart Rate Monitoring in Smart Homes: An Angular-Free Approach with an FMCW Radar.

This paper proposes a new approach for wide angle monitoring of vital signs in smart home applications. The person is tracked using an indoor radar. Upon detecting the person to be static, the radar automatically focuses its beam on that location, and subsequently breathing and heart rates are extracted from the reflected signals using continuous wavelet transform (CWT) analysis. In this way, leveraging the radar's on-chip processor enables real-time monitoring of vital signs across varying angles. In our experiment, we employ a commercial multi-input multi-output (MIMO) millimeter-wave FMCW radar to monitor vital signs within a range of 1.15 to 2.3 m and an angular span of -44.8 to +44.8 deg. In the Bland-Altman plot, the measured results indicate the average difference of -1.5 and 0.06 beats per minute (BPM) relative to the reference for heart rate and breathing rate, respectively.

A Retrospective Analysis of Leadership, Awardees, and Member Gender Representation of the Canadian Society for Immunology.

The Canadian Society for Immunology (CSI) established a formal Equity, Diversity, and Inclusion (EDI) Committee with the goal of providing EDI advocacy and leadership within the CSI, as well as in the broader scientific community. A first task of this committee was to review the publicly available historical data on gender representation within the CSI's membership, leadership, award recipients, and conference chairs/presenters as a step in establishing a baseline reference point and monitoring the trajectory of future success in achieving true inclusion. We found that, except for overall membership and a specific subset of awards, all categories showed a historical bias toward men, particularly prior to 2010. Bias persists in various categories, evident even in recent years. However, we note an encouraging trend toward greater gender parity, particularly in the roles of President, symposium presenters, and workshop chairs, especially from 2017 onward. We present these findings as well as our recommendations to enhance inclusivity. These include a more comprehensive collection and secure storage of self-identification data, emphasis on EDI as an essential component of all annual meeting activities, and innovative measures of outreach, collaboration, and leadership with the aim of making the CSI a model for improving EDI in other professional research societies.

A systematic scoping review of the latest data on orthobiologics in the surgical treatment of non-union.

INTRODUCTION: Recent studies have shown a growing concern regarding the cost-effectiveness and the lack of supporting data for the biologic agents that are being increasingly used in the orthopedic field. Our aim was to conduct a systematic scoping review of recent publications (last five years) on the use of orthobiologics to treat fracture non-union and summarize the latest available data. PATIENTS AND METHODS: The inclusion criteria for this review were articles published in English, from 2016 to 2022, and focusing on the use of orthobiologics for the surgical treatment of non-union. Searches were conducted in March 2023 using Pubmed/MEDLINE and Embase. Studies on spinal fusion or gene therapy were excluded. Reviews, case reports with five cases or less, conference proceedings, preliminary reports, pediatric or non-human studies were excluded as well. RESULTS: The search found 1807 articles, 15 were eligible after PRISMA checklist and exclusions. The evidence was heterogenous and there was only one level II RCT. Recent data suggests that bone morphogenic protein (BMP-2) products could be effective for septic and aseptic tibial non-unions. However, the evidence was not conclusive regarding BMP-7, plasma rich platelets (PRP), stem cells or demineralized bone matrix (DBM). DISCUSSION: Every non-union case is different in terms of bone defect, biology, mechanical stability, surgical technique and host factors, which contributes to the conflicting reports on the efficacy of orthobiologics in the literature. We might never see a level 1, high powered and robust study defining the efficacy, safety profile and cost-effectiveness of such products. LEVEL OF EVIDENCE: IV.

Discrepancies between transcutaneous and estimated glomerular filtration rates in rats with chronic kidney disease.

Accurate assessment of the glomerular filtration rate (GFR) is crucial for researching kidney disease in rats. Although validation of methods that assess GFR is crucial, large-scale comparisons between different methods are lacking. Both transcutaneous GFR (tGFR) and a newly developed estimated GFR (eGFR) equation by our group provide a low-invasive approach enabling repeated measurements. The tGFR is a single bolus method using FITC-labeled sinistrin to measure GFR based on half-life of the transcutaneous signal, whilst the eGFR is based on urinary sinistrin clearance. Here, we retrospectively compared tGFR, using both 1- and 3- compartment models (tGFR_1c and tGFR_3c, respectively) to the eGFR in a historic cohort of 43 healthy male rats and 84 male rats with various models of chronic kidney disease. The eGFR was on average considerably lower than tGFR-1c and tGFR-3c (mean differences 855 and 216 µL/min, respectively) and only 20 and 47% of measurements were within 30% of each other, respectively. The relative difference between eGFR and tGFR was highest in rats with the lowest GFR. Possible explanations for the divergence are problems inherent to tGFR, such as technical issues with signal measurement, description of the signal kinetics, and translation of half-life to tGFR, which depends on distribution volume. The unknown impact of isoflurane anesthesia used in determining mGFR remains a limiting factor. Thus, our study shows that there is a severe disagreement between GFR measured by tGFR and eGFR, stressing the need for more rigorous validation of the tGFR and possible adjustments to the underlying technique.