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.

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.

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.

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 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 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 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.

A novel fragment specific classification of complex olecranon fractures: 3-dimensional model design, radiological validation, and proposed surgical algorithm.

BACKGROUND: Current classifications for proximal ulna fracture patterns rely on qualitative data and cannot inform surgical planning. We propose a new classification system based on a biological and anatomical stress analysis. Our hypothesis is that fragment types in complex fractures can be predicted by the tendon and ligament attachments on the proximal ulna. METHODS: First, we completed a literature review to identify quantitative data on proximal ulna soft tissue attachments. On this basis, we created a 3-dimensional model of ulnar anatomy with SliceOMatic and Catia V5R20 software and determined likely locations for fragments and fracture lines. The second part of the study was a retrospective radiological study. A level-1 trauma radiological database was used to identify computed tomography scans of multifragmentary olecranon fractures from 2009 to 2021. These were reviewed and classified according to the "fragment specific" classification and compared to the Mayo and the Schatzker classifications. RESULTS: Twelve articles (134 elbows) met the inclusion criteria and 7 potential fracture fragments were identified. The radiological study included 67 preoperative computed tomography scans (mean 55 years). The fragments identified were the following: posterior (40%), intermediate (42%), tricipital (100%), supinator crest (25%), coronoid (18%), sublime tubercle (12%), and anteromedial facet (18%). Eighteen cases (27%) were classified as Schatzker D (comminutive) and 21 (31%) Mayo 2B (stable comminutive). Inter-rater correlation coefficient was 0.71 among 3 observers. CONCLUSION: This proposed classification system is anatomically based and considers the deforming forces from ligaments and tendons. Having a more comprehensive understanding of complex proximal ulna fractures would lead to more accurate fracture evaluation and surgical planning.

New Pathophysiological Insights from Serum Proteome Profiling in Equine Atypical Myopathy.

Equine atypical myopathy (AM) is a severe environmental intoxication linked to the ingestion of protoxins contained in seeds and seedlings of the sycamore maple (Acer pseudoplatanus) in Europe. The toxic metabolites cause a frequently fatal rhabdomyolysis syndrome in grazing horses. Since these toxic metabolites can also be present in cograzing horses, it is still unclear as to why, in a similar environmental context, some horses show signs of AM, whereas others remain clinically healthy. Label-free proteomic analyses on the serum of 26 diseased AM, 23 cograzers, and 11 control horses were performed to provide insights into biological processes and pathways. A total of 43 and 44 differentially abundant proteins between "AM vs cograzing horses" and "AM vs control horses" were found. Disease-linked changes in the proteome of different groups were found to correlate with detected amounts of toxins, and principal component analyses were performed to identify the 29 proteins representing a robust AM signature. Among the pathway-specific changes, the glycolysis/gluconeogenesis pathway, the coagulation/complement cascade, and the biosynthesis of amino acids were affected. Sycamore maple poisoning results in a combination of inflammation, oxidative stress, and impaired lipid metabolism, which is trying to be counteracted by enhanced glycolysis.

Centering Equity in the Nation's Weather, Water, and Climate Services.

Water, weather, and climate affect everyone. However, their impacts on various communities can be very different based on who has access to essential services and environmental knowledge. Structural discrimination, including racism and other forms of privileging and exclusion, affects people's lives and health, with ripples across all sectors of society. In the United States, the need to equitably provide weather, water, and climate services is uplifted by the Justice40 Initiative (Executive Order 14008), which mandates 40% of the benefits of certain federal climate and clean energy investments flow to disadvantaged communities. To effectively provide such services while centering equity, systemic reform is required. Reform is imperative given increasing weather-related disasters, public health impacts of climate change, and disparities in infrastructure, vulnerabilities, and outcomes. It is imperative that those with positional authority and resources manifest responsibility through (1) recognition, inclusion, and prioritization of community expertise; (2) the development of a stronger and more representative and equitable workforce; (3) communication about climate risk in equitable, relevant, timely, and culturally responsive ways; and (4) the development and implementation of new models of relationships between communities and the academic sector.

Neural recordings can differentiate between spontaneously metastasizing melanomas and melanomas with low metastatic potential.

Multiple studies report that melanomas are innervated tumors with sensory and sympathetic fibers where these neural fibers play crucial functional roles in tumor growth and metastasis with branch specificity. Yet there is no study which reports the direct neural recording and its pattern during in-vivo progression of the cancer. We performed daily neural recordings from male and female mice bearing orthotopic metastasizing- melanomas and melanomas with low metastatic poential, derived from B16-F10 and B16-F1 cells, respectively. Further, to explore the origins of neural activity, 6-Hydroxidopamine mediated chemical sympathectomy was performed followed by daily microneurographic recordings. We also performed the daily bioluminescent imaging to track in vivo growth of primary tumors and distant metastasis to the cranial area. Our results show that metastasizing tumors display high levels of neural activity while tumors with low metastatic potential lack it indicating that the presence of neural activity is linked to the metastasizing potential of the tumors. Moreover, the neural activity is not continuous over the tumor progression and has a sex-specific temporal patterns where males have two peaks of high neural activity while females show a single peak. The neural peak activity originated in peripheral sympathetic nerves as sympathectomy completely eliminated the peak activity in both sexes. Peak activities were highly correlated with the distant metastasis in both sexes. These results show that sympathetic neural activity is crucially involved in tumor metastasis and has sex-specific role in malignancy initiation.

Association of Frailty and Cardiopulmonary Resuscitation Outcomes in Older U.S. Veterans.

Objectives: Determine the association between frailty and immediate survival of cardiopulmonary resuscitation (CPR) in older Veterans. Secondary outcomes: compare in-hospital mortality, duration of resuscitation efforts, hospital and intensive care unit (ICU) length of stay, neurologic outcomes, and discharge disposition between frail and non-frail Veterans. Methods: Retrospective cohort study including Veterans 50 years and older, who were "Full Code" and had in-hospital cardiac arrest between 7/1/2017 and 6/30/2020, at the Miami VAMC. Frailty Index for the VA (VA-FI) was used to determine frailty status. Immediate Survival was determined by return of spontaneous circulation (ROSC) and in-hospital mortality was determined by all-cause mortality. We compared outcomes between frail and non-frail Veterans using chi-square test. After adjusting for age, gender, race, and previous hospitalizations, we used multivariate binomial logistic regression with 95% confidence intervals to analyze the relationship between immediate survival and frailty, and in-hospital mortality and frailty. Results: 91% Veterans were non-Hispanic, 49% Caucasian, 96% male, mean age 70.7 ± 8.5 years, 73% frail and 27% non-frail. Seventy-six (65.5%) Veterans had ROSC, without difference by frailty status (P = .891). There was no difference based on frailty status of in-hospital mortality, discharge disposition, or neurologic outcomes. Frail and non-frail Veterans had resuscitation efforts lasting the same amount of time. Conclusions and Implications: CPR outcomes were not different depending on frailty status in our Veteran population. With these results, we cannot use frailty - as measured by the VA-FI - as a prognosticator of CPR outcomes in Veterans.

Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model.

OBJECTIVE: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. METHODS: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes. RESULTS: We found that the spike-suppressive effects of high-frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 µA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. SIGNIFICANCE: These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti-seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy. PLAIN LANGUAGE SUMMARY: In this study, we tested how electrical pulses in the brain can help control seizures in mice. We found that the electrode's placement and the stimulation amplitude had a large effect on outcomes. Some brain regions, notably nearby CA1 and CA3, responded positively with reduced seizure-like activities, while others showed increased activity. These findings emphasize that choosing the right spot for the electrode and adjusting the strength of electrical pulses are both crucial when considering neurostimulation treatments for epilepsy.

Corrective Open-wedge Valgus Proximal Humerus Lengthening Osteotomy. Technique and Case Series.

Symptomatic varus malunion after proximal humeral fractures is associated with weakness and painful limitation of shoulder range of motion. When there is conformity of the articular surface and no avascular necrosis, a head-preserving procedure is best indicated. Arthroscopic arthrolysis, subacromial decompression, and tuberoplasty have been described for the treatment of mild deformity. In cases with more severe deformity, corrective extracapsular lateral closing wedge valgus osteotomy has been reported as a reliable treatment option, in terms of both pain relief and improved function. While this procedure adequately restores rotator cuff tensioning, it is associated with a shortening of the lever arm to the deltoid muscle, secondary to a loss of humeral length. We describe our technique and results with a vascular-sparing, medial open-wedge osteotomy, using a structural allograft and lateral locking plate. In our opinion, this procedure is safe and effective, with the potential to improve functional outcomes in young and active patients.

Selective chronic recording in small nerve fascicles of sciatic nerve with carbon nanotube yarns in rats.

Objective. The primary challenge faced in the field of neural rehabilitation engineering is the limited advancement in nerve interface technology, which currently fails to match the mechanical properties of small-diameter nerve fascicles. Novel developments are necessary to enable long-term, chronic recording from a multitude of small fascicles, allowing for the recovery of motor intent and sensory signals.Approach. In this study, we analyze the chronic recording capabilities of carbon nanotube yarn electrodes in the peripheral somatic nervous system. The electrodes were surgically implanted in the sciatic nerve's three individual fascicles in rats, enabling the recording of neural activity during gait. Signal-to-noise ratio (SNR) and information theory were employed to analyze the data, demonstrating the superior recording capabilities of the electrodes. Flat interface nerve electrode and thin-film longitudinal intrafascicular electrode electrodes were used as a references to assess the results from SNR and information theory analysis.Main results. The electrodes exhibited the ability to record chronic signals with SNRs reaching as high as 15 dB, providing 12 bits of information for the sciatic nerve, a significant improvement over previous methods. Furthermore, the study revealed that the SNR and information content of the neural signals remained consistent over a period of 12 weeks across three different fascicles, indicating the stability of the interface. The signals recorded from these electrodes were also analyzed for selectivity using information theory metrics, which showed an information sharing of approximately 1.4 bits across the fascicles.Significance. The ability to safely and reliably record from multiple fascicles of different nerves simultaneously over extended periods of time holds substantial implications for the field of neural and rehabilitation engineering. This advancement addresses the limitation of current nerve interface technologies and opens up new possibilities for enhancing neural rehabilitation and control.

Development and validation of a human bronchial epithelial spheroid model to study respiratory toxicity in vitro.

The use of laboratory animals in research has been extensively criticized. While most of the critique has been centered around the ethical aspect, also the economic and scientific aspects have been frequently mentioned as points of concern. As a result, the use of alternative methods has gradually become more enticing. The most used alternatives to laboratory animals are the 2D monolayer cell cultures. However, the limited translatability of these monolayer cell cultures to in vivo has led to the development of 3D cell cultures that are believed to better capture the in vivo physiology and pathology. Here we report on the development of a physiologically more relevant 3D cell model (spheroids) comprised of human bronchial epithelial (16HBE14o-) cells, for use in respiratory toxicity research. Culturing 16HBE14o-cells as hanging-drops led to the formation of stable spheroids which showed an increased expression of CLDN1 when compared to 2D monolayer cultured cells. In addition, cell-cycle analysis revealed an increased sub-G0 population and signs of G0/G1 arrest in spheroids. Afterwards, standard operating procedures (SOPs) were established, and existing protocols optimized, for compatibility with spheroids. Spheroids were successfully used to assess cytotoxicity, genotoxicity, apoptosis/necrosis, and oxidative stress after exposure to known cytotoxic or genotoxic compounds. The development of the bronchial epithelial spheroids and the establishment of SOPs can contribute to a more reliable toxicity assessment of chemicals and may aid in bridging the gap between in vivo and in vitro experiments.

Canadian medical student knowledge and attitudes toward female genital mutilation.

Background: Despite female genital mutilation/cutting (FGM/C) practices being an illegal form of gender-based violence in Canada, this practice impacts many Canadians. Lack of education and training among Canadian health-care providers has resulted in systematic barriers to care. Awareness and FGM/C-related education among Canadian health-care providers must be urgently assessed. Methods: Canadian medical students were recruited to complete an anonymous survey via E-mails distributed through their schools' student organization between January and March 2021. We evaluated student understanding of FGM/C, attitudes toward medicalization and legislation, and prior clinical experience using multiple choice, Likert scale, and open-response questions. Results: Respondents (n = 135) performed poorly on knowledge assessment questions (mean percent correct <50%). Only 10.4% of respondents indicated knowing how to involve appropriate authorities when necessary, and most never evaluate FGM/C in patient history (86.7%) or clinical examination (57.1%). Subgroup analysis revealed that prior education significantly improved knowledge scores and influenced students' behaviors and attitudes. About 92.2% of respondents supported the integration of FGM/C curricula in undergraduate medical education. Discussion: This study reveals that Canadian medical students have a poor understanding of FGM/C and are not prepared to identify affected patients or intervene when necessary. These results provide rationale for the implementation of FGM/C-learning modules in undergraduate medicine.