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Study Design: Retrospective cohort study of prospectively accrued data., Objective: To evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach., Summary of Background Data: The influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data., Methods: Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy., Results: A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P =0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy ( P =0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches., Conclusion: The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM., Level of Evidence: Therapeutic Level-II., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

An Objective Structured Practical Examination (OSPE) is an effective and robust, but resource-intensive, means of evaluating anatomical knowledge. Since most OSPEs employ short answer or fill-in-the-blank style questions, the format requires many people familiar with the content to mark the examinations. However, the increasing prevalence of online delivery for anatomy and physiology courses could result in students losing the OSPE practice that they would receive in face-to-face learning sessions. The purpose of this study was to test the accuracy of Decision Trees (DTs) in marking OSPE questions as a first step to creating an intelligent, online OSPE tutoring system. The study used the results of the winter 2020 semester final OSPE from McMaster University's anatomy and physiology course in the Faculty of Health Sciences (HTHSCI 2FF3/2LL3/1D06) as the data set. Ninety percent of the data set was used in a 10-fold validation algorithm to train a DT for each of the 54 questions. Each DT was comprised of unique words that appeared in correct, student-written answers. The remaining 10% of the data set was marked by the generated DTs. When the answers marked by the DT were compared to the answers marked by staff and faculty, the DT achieved an average accuracy of 94.49% across all 54 questions. This suggests that machine learning algorithms such as DTs are a highly effective option for OSPE grading and are suitable for the development of an intelligent, online OSPE tutoring system., (© 2023 The Authors. Anatomical Sciences Education published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Background and Objectives: Interhospital transfer from community hospitals to centers specialized in managing traumatically injured individuals can strain patients, healthcare systems, and delay appropriate care. The purpose was to compare long-term neurological outcomes in transferred or directly admitted patients with traumatic spinal cord injury (SCI)., Methods: An ambispective cohort study was conducted using prospectively collected data (between 2005 and 2018) from 11 specialized level 1 trauma centers across the United States and Canada. All patients who underwent surgical management for SCI were included and placed into 2 comparison cohorts: (1) direct admission and (2) transfer from intermediate hospital. Outcomes were change in American Spinal Injury Association Impairment Scale grade and its components: upper-extremity motor, lower-extremity motor, pinprick, and light touch scores from baseline (assessed ≤72 hours after injury) to follow-up (12-52 weeks). Nearest-neighbor 1:1 propensity score matching between the transferred and directly admitted cohorts was performed. Paired analysis using McNemar's test and paired Student's t -test was used to determine the extent of the difference in neurological outcomes., Results: Nine hundred seventy patients (55.5% male, 55.2 ± 18.9 years) with traumatic SCI were directly admitted to a specialized trauma center (N = 474, 48.9%) or transferred from an intermediate hospital (N = 496, 51.1%). After propensity score matching, 283 pairs were matched. Compared with a matched cohort of transferred patients, American Spinal Injury Association Impairment Scale grade improved more in directly admitted patients (56.2% vs 46.3%, P = .024), as did upper-extremity motor score (13.7 ± 12.8 vs 10.4 ± 11.5, P = .018) and light touch score (22.0 ± 29.7 vs 16.9 ± 26.6, P = .034)., Conclusion: Patients with SCI directly admitted to specialized trauma centers have greater neurological recovery compared with patients transferred from an intermediate hospital. Feasibility of direct admission to a center specialized in the management of acute SCI through implementation of a standardized code program must be further investigated., Level of Evidence: Therapeutic level II., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Pulsar Timing Array experiments probe the presence of possible scalar or pseudoscalar ultralight dark matter particles through decade-long timing of an ensemble of galactic millisecond radio pulsars. With the second data release of the European Pulsar Timing Array, we focus on the most robust scenario, in which dark matter interacts only gravitationally with ordinary baryonic matter. Our results show that ultralight particles with masses 10^{-24.0}  eV≲m≲10^{-23.3}  eV cannot constitute 100% of the measured local dark matter density, but can have at most local density ρ≲0.3  GeV/cm^{3}.

Objective: Mechanism of injury is a largely understudied descriptor of acute traumatic spinal cord injury (tSCI). This study sought to compare the impact of high-energy and low-energy mechanisms of injury in neurological outcomes of cervical sensorimotor complete tSCI., Methods: Patients with tSCI were identified in 4 prospective, multicenter clinical trials and registries. American Spinal Injury Association Impairment Scale (AIS) grade was assessed ≤ 72 hours postinjury and followed up between 12 to 52 weeks. Patients were included if they had a cervical and sensorimotor complete (AIS-A) injury at baseline. Study outcomes were change in AIS grade and lower extremity motor, upper extremity motor, and total motor scores. Propensity score matching between high-energy mechanisms of injury (HEMI; e.g. , motor vehicle collisions) and low-energy mechanisms of injury (LEMI; e.g. , falls) groups was performed. Adjusted groups were compared with paired t-tests and McNemar test., Results: Of 667 patients eligible for inclusion, 523 experienced HEMI (78.4%). HEMI patients were younger, had lower body mass index, more associated fractures or dislocations, and lower baseline lower extremity motor scores. After propensity score matching of these baseline variables, 118 pairs were matched. HEMI patients had a significantly worse motor recovery from baseline to follow-up based on their diminished change in upper extremity motor scores and total motor scores., Conclusion: Cervical sensorimotor complete tSCIs from HEMI were associated with significantly lower motor recovery compared to LEMI patients. Our findings suggest that mechanism of injury should be considered in modelling prognosis and in understanding the heterogeneity of outcomes after acute tSCI.

The use of direct factor Xa inhibitors rivaroxaban and apixaban (XABANs) has rapidly increased; however, there is no validated test available to monitor the effect on hemostasis. This study aims to assess how hemostatic management based on the Rapid Thromboelastography (R-TEG) variable activated clotting time (ACT) of XABAN patients with ongoing bleedings or in need for acute surgical intervention, affected patient outcome. A total of 343 XABAN patients were included in the main analysis together with 50 healthy volunteers to validate the reference value for ACT. An ACT >120 s (s) was defined as having XABAN-induced coagulopathy. Sixty-five percent of the XABAN patients presented with R-TEG ACT within the normal reference. Patients with XABAN-induced coagulopathy had a significantly increased risk of severe bleeding. Significantly more patients with extra-cerebral bleeding (ECB) and ACT above 120 s were transfused with five red blood cell (RBC) units or more compared to patients with ACT at 120 s or below (17% vs. 3%, p  <.05). Significantly more XABAN-patients with ACT above 120 s received pro-hemostatic intervention with prothrombin complex concentrate (PCC) when compared to those with ACT at 120 s or below (ECB: 2% vs. 8%, p  =.03, intracranial hemorrhage: 25% vs. 68%, p  <.00). Patients who received PCC had a higher 30- and 90-day mortality compared to the rest of the cohort (16% vs. 6%, p  = .02 and 21% vs. 7%, p  =.00). Patients with XABAN-induced coagulopathy as evaluated by R-TEG ACT presented with more severe bleeding and higher transfusion requirements when compared to those with ACT in the normal range. This suggests that R-TEG ACT measurement in XABAN patients with active hemorrhage or in need for acute surgery may be of clinical value.

Objective: To compare the immediate response of nursing home residents to dog visits with or without an activity, and the impact of cognitive ability., Methods: In a randomly controlled trial, 174 nursing home residents were allocated to 12 bi-weekly 10-minute visits: either ordinary dog visits (D, n = 57, 49 analysed), dog visits with an activity (DA, n = 56, 48 analysed), or visits with activity but no dog (A, n = 61, 54 analysed). We recorded frequency and duration of residents' verbal and physical interactions with the dog and persons. Data were analysed in three periods of four visits (period 1-3) as binomial variables (generalised linear models) or durations (non-parametric statistics)., Results: Both visit type and impairment level affected the likelihood of interacting with the dog (D and DA). In some periods increased cognitive impairment lowered odds of touching the dog in DA visits (period 1: F1,85 = 5.17, P < 0.05) and talking to it directly (period 1: F1,90 = 4.60, P < 0.05; period 3: F1,87 = 5.34, P < 0.05). Throughout, residents talked less to persons during DA visits compared to D and A (P = 0.01-0.05), and level of cognitive impairment correlated negatively with talk duration (P < 0.001). Generally, high cognitive impairment level lowered odds of interacting with (period 1: F1,89 = 7.89, P < 0.01; period 2: F1,97 = 6.76, P = 0.01; period 3: F1,92 = 13.57, P < 0.001) and talking about the activities (period 1: F1,89 = 13.78, P <0.001; period 2: F1,88 = 3.27, P = 0.07; period 3: F1,86 = 3.88, P = 0.05)., Conclusion: Visits without specific activities stimulated residents to interact with the dog, whereas increasing the complexity of dog visits by adding activities resulted in less interaction with the dog for severely impaired residents. The optimal dog visit for the less cognitively impaired residents could include activities and thereby a possibility to interact with the dog in different ways, whereas for severely impaired residents, just being with the dog seems more appropriate., Competing Interests: The authors have declared that no competing interests exist.

As post-secondary education migrates online, developing and evaluating new avenues for assessment in anatomy is paramount. Three-dimensional (3D) visualization technology is one area with the potential to augment or even replace resource-intensive cadaver use in anatomical education. This manuscript details the development of a smartphone application, entitled "Virtual Reality Bell-Ringer (VRBR)," capable of displaying monoscopic two-dimensional (2D) or stereoscopic 3D images with the use of an inexpensive cardboard headset for use in spot examinations. Cadaveric image use, creation, and pinning processes are explained, and the source code is provided. To validate this tool, this paper compares traditional laboratory-based spot examination assessment stations against those administered using the VRBR application to test anatomical knowledge. Participants (undergraduate, n = 38; graduate, n = 13) completed three spot examinations specific to their level of study, one in each of the modalities (2D, 3D, laboratory) as well as a mental rotation test (MRT), Stereo Fly stereotest, and cybersickness survey. Repeated measures ANCOVA suggested participants performed significantly better on laboratory and 3D stations compared to 2D stations. Moderate to severe cybersickness symptoms were reported by 63% of participants in at least one category while using the VRBR application. Highest reported symptoms included: eye strain, general discomfort, difficulty focusing, and difficulty concentrating. Overall, the VRBR application is a promising tool for its portability, affordability, and accessibility. Due to reported cybersickness and other technical limitations, the use of VRBR as an alternative to cadaveric specimens presents several challenges when testing anatomy knowledge that must be addressed before widespread adoption., (© 2021 American Association for Anatomy.)

MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression posttranscriptionally by binding to the 3' untranslated regions of their target mRNAs. The evolutionarily conserved microRNA-125a (miR-125a) is highly expressed in both murine and human hematopoietic stem cells (HSCs), and previous studies have found that miR-125 strongly enhances self-renewal of HSCs and progenitors. In this study we explored whether temporary overexpression of miR-125a would be sufficient to permanently increase HSC self-renewal or, rather, whether persistent overexpression of miR-125a is required. We used three complementary in vivo approaches to reversibly enforce expression of miR-125a in murine HSCs. Additionally, we interrogated the underlying molecular mechanisms responsible for the functional changes that occur in HSCs on overexpression of miR-125a. Our data indicate that continuous expression of miR-125a is required to enhance HSC activity. Our molecular analysis confirms changes in pathways that explain the characteristics of miR-125a overexpressing HSCs. Moreover, it provides several novel putative miR-125a targets, but also highlights the complex molecular changes that collectively lead to enhanced HSC function., Competing Interests: Conflict of interest disclosure No financial interest/relationships with financial interest relating to the topic of this article have been declared., (Copyright © 2020 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Introduction: Randomized controlled trials (RCTs) have been critical in evaluating the safety and efficacy of functional neurosurgery interventions. Given this, we sought to systematically assess the quality of functional neurosurgery RCTs., Methods: We used a database of neurosurgical RCTs (trials published from 1961 to 2016) to identify studies of functional neurosurgical procedures (N = 48). We extracted data on the design and quality of these RCTs and quantified the quality of trials using Jadad scores. We categorized RCTs based on the device approval status at the time of the trial and tested the association of device approval status with trial design and quality parameters., Results: Of the 48 analyzed functional neurosurgery RCTs, the median trial size was 34.5 patients with a median age of 51. The most common indications were Parkinson's disease (N = 20), epilepsy (N = 10), obsessive-compulsive disorder (N = 4), and pain (N = 4). Most trials reported inclusion and exclusion criteria (95.8%), sample size per arm (97.9%), and baseline characteristics of the patients being studied (97.9%). However, reporting of allocation concealment (29.2%), randomization mode (66.7%), and power calculations (54.2%) were markedly less common. We observed that trial quality has improved over time (Spearman r, 0.49). We observed that trials studying devices with humanitarian device exemption (HDE) and experimental indications (EI) tended to be of higher quality than trials of FDA-approved devices (p = 0.011). A key distinguishing quality characteristic was the proportion of HDE and EI trials that were double-blinded, compared to trials of FDA-approved devices (HDE, 83.3%; EI, 69.2%; FDA-approved, 35.3%). Although more than one-third of functional neurosurgery RCTs reported funding from industry, no significant association was identified between funding source and trial quality or outcome., Conclusion: The quality of RCTs in functional neurosurgery has improved over time but reporting of specific metrics such as power calculations and allocation concealment requires further improvement. Device approval status but not funding source was associated with trial quality., (© 2019 International Neuromodulation Society.)

Transvenous approaches for pacemaker and defibrillator lead insertion offer numerous advantages over epicardial techniques. Although the cephalic, axillary, and subclavian veins are most commonly used in clinical practice, they each offer their own set of advantages and disadvantages that leave their usage dependent on patient anatomy and physician preference. Alternative methods using the upper and lower venous circulation have been described when these veins are not available or practical for lead insertion. Until current technology is superseded by leadless pacing systems, the search for the optimal lead insertion technique continues., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Long QT Syndrome 3 (LQTS3) arises from gain-of-function Na v 1.5 mutations, prolonging action potential repolarisation and electrocardiographic (ECG) QT interval, associated with increased age-dependent risk for major arrhythmic events, and paradoxical responses to β-adrenergic agents. We investigated for independent and interacting effects of age and Scn5a+/ΔKPQ genotype in anaesthetised mice modelling LQTS3 on ECG phenotypes before and following β-agonist challenge, and upon fibrotic change. Prolonged ventricular recovery was independently associated with Scn5a+/ΔKPQ and age. Ventricular activation was prolonged in old Scn5a+/ΔKPQ mice (p = 0.03). We associated Scn5a+/ΔKPQ with increased atrial and ventricular fibrosis (both: p < 0.001). Ventricles also showed increased fibrosis with age (p < 0.001). Age and Scn5a+/ΔKPQ interacted in increasing incidences of repolarisation alternans (p = 0.02). Dobutamine increased ventricular rate (p < 0.001) and reduced both atrioventricular conduction (PR segment-p = 0.02; PR interval-p = 0.02) and incidences of repolarisation alternans (p < 0.001) in all mice. However, in Scn5a+/ΔKPQ mice, dobutamine delayed the changes in ventricular repolarisation following corresponding increases in ventricular rate. The present findings implicate interactions between age and Scn5a+/ΔKPQ in prolonging ventricular activation, correlating them with fibrotic change for the first time, adding activation abnormalities to established recovery abnormalities in LQTS3. These findings, together with dynamic electrophysiological responses to β-adrenergic challenge, have therapeutic implications for ageing LQTS patients.

National Danish guidelines for the diagnosis and treatment of irritable bowel syndrome (IBS) in adult patients in secondary and tertiary care have been approved by the Danish Society for Gastroenterology and Hepatology. IBS can be a positive diagnosis in patients fulfilling the Rome III criteria for IBS with no alarm signals, a normal physical examination and a normal CRP and hemoglobin. In patients < 40 years with IBS and diarrhea, a normal fecal calprotectin excludes inflammatory bowel disease with a high probability. Patients with IBS and diarrhea should be tested for celiac disease. Endoscopy is not routinely recommended. The therapeutic gain of various treatment modalities is small and most likely overestimated in older studies. However, side effects are usually mild which may justify empirical treatment. The choice of therapy based on IBS subtyping is pragmatic and there are only few trials as guidance. The significance of previous failure with another treatment modality is unclear. There is a lack of long-term treatment trials. The generalizability of the trials is poor, mainly due to selection bias., (Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)