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Purpose Medical schools have faced various challenges in preparing their clinical students for the frontlines of a pandemic. This study investigated medical students’ satisfaction with their institutions during the coronavirus disease 2019 (COVID-19) pandemic with the intention of guiding educators in future public health crises. Methods In this cross-sectional study surveying students in clinical rotations, the primary outcome was overall satisfaction regarding medical schools’ responses to the pandemic, and the four secondary outcomes were school communication, exposure to COVID-19, availability of personal protective equipment, and access to COVID-19 testing. Results The survey was distributed to ten medical schools, of which 430 students responded for a response rate of 13.0%. While most students were satisfied (61.9%, n=266) with their schools’ response, more than one in five (21.9%, n=94) were dissatisfied. Among the four secondary outcomes, communication with students was most predictive of overall satisfaction. Conclusion In future crises, schools can best improve student satisfaction by prioritizing timely communication.

Abstract Background To investigate the effects of the U.S. Preventive Services Task Force’s (USPSTF) 2012 recommendation against prostate-specific antigen (PSA)-based screening for prostate cancer on survival disparities based on insurance status. Prior to the USPSTF’s 2012 screening recommendation, previous studies found that insured patients with prostate cancer had better outcomes than uninsured patients. Methods Using the SEER 18 database, we examined prostate cancer-specific survival (PCSS) based on diagnostic time period and insurance status. Patients were designated as belonging to the pre-USPSTF era if diagnosed in 2010–2012 or post-USPSTF era if diagnosed in 2014–2016. PCSS was measured with the Kaplan–Meier method, while disparities were measured with the Cox proportional hazards model. Results During the pre-USPSTF era, uninsured patients experienced worse PCSS compared to insured patients (adjusted HR 1.256, 95% CI 1.037–1.520, p = 0.020). This survival disparity was no longer observed during the post-USPSTF era as a result of decreased PCSS among insured patients combined with unchanged PCSS among uninsured patients (adjusted HR 0.946, 95% CI 0.642–1.394, p = 0.780). Conclusions Although the underlying reasons are not clear, the USPSTF’s 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without affecting the survival of uninsured patients.

Background: Clinical evidence suggests that chemotherapeutic agents are associated with neuropathy and peripheral autonomic dysfunction. However, the possible effects of neoadjuvant chemotherapy on intraoperative temperature remain poorly characterised. Methods: We evaluated patients who underwent a mastectomy for breast cancer between April 2016 and July 2020. Propensity scores were used to match patients who received neoadjuvant chemotherapy with those who did not, and intraoperative core temperature patterns were analysed in the matched cohort. The independent associations between vasopressor use and heart rate during general anaesthesia in the matched cohort were also analysed. Results: Data from 1764 patients were analysed (882 patients in each group). Both groups presented a similar pattern of heat redistribution and subsequent rewarming; however, the neoadjuvant chemotherapy group did not reach the same intraoperative plateau temperature as the group that did not receive prior chemotherapy, with differences of up to 0.4°C (95% confidence interval: 0.11–0.63°C; P=0.005). In a subgroup analysis, neuropathy in patients who received neoadjuvant chemotherapy was associated with increased use of vasopressors and higher heart rate. Conclusions: In patients with breast cancer, neoadjuvant chemotherapy is associated with lower plateau core temperatures, increased vasopressor use, and higher heart rates during general anaesthesia, which is more severe in the presence of neuropathy.

Abstract Since 2004, multiple blockbuster drugs have been approved for men with metastatic prostate cancer. Nevertheless, it has been reported that no improvement in survival was observed between 2004 and 2009. Herein, we have analyzed the SEER database to assess the survival outcome of metastatic prostate cancer patients since 2000. The results demonstrated that there was an improvement in both overall and prostate cancer‐specific survival for 4 months among men diagnosed with metastatic prostate cancer from 2010 to 2016 when compared to those in the pre‐2010 period. Interestingly, this survival benefit was limited to patients with bone and visceral metastasis (M1b and M1c stages). Collectively, our observation suggests that despite the new treatment agents such as second‐line antiandrogen therapies introduced in the modern era, the improvement in survival of metastatic prostate cancer patients has been surprisingly small.

Acute posterior multifocal placoid pigment epitheliopathy (APMPEE) is a chorioretinal inflammatory disease of unknown origin. Patients usually present with a rapid loss of central/paracentral vision over the course of a week in both eyes. The fundus exhibits rapid appearance of multiple deep subretinal yellow-white, flat lesions at the RPE/choriocapillaris level. This in turn causes changes of both the ellipsoid zone and RPE which can result in permanent central vision loss. The pathogenesis is controversial but is associated with a recent viral illness and can involve the central nervous system with concern for cerebral vasculitis. Rare reports of APMPEE associated with systemic vasculitis such as Wegener’s granulomatosis and malignancy such as clear cell renal carcinoma have been reported. We report a case of APMPEE with concurrent diagnosis of gastrointestinal stromal tumor and Hurthle cell tumor. While such association may well be coincidental, the near simultaneous presentation raised our suspicion for potential association.

Myocardial fibrosis is a crucial marker of heart muscle injury in several heart disease like myocardial infarction, cardiomyopathies, and atrial fibrillation (AF). Fibrosis and associated scarring (dense fibrosis) are also vital for assessing heart muscle pre- and post-intervention, such as evaluating left atrial (LA) fibrosis/scarring in patients undergoing catheter ablation for AF. Although cardiac MRI is the gold standard for fibrosis assessment, current quantification methods are unreliable due to their reliance on variable thresholding and sensitivity to MRI uncertainties, lacking standardization and reproducibility. Importantly, current methods focus solely on quantifying fibrosis volume ignoring the unique MRI characteristics of fibrosis density and unique distribution, that could better inform on disease severity. To address these issues, we propose a novel threshold-free self-calibrating probabilistic method called "Fibrosis Signatures." This method efficiently encodes ∼9 billion MRI intensity co-disparities per scan into standardized probability density functions, deriving a unique MRI fibrosis signature index (FSI). The FSI index quantitatively encodes fibrosis/scar extent, density, and distribution patterns simultaneously, providing a detailed assessment of burden/severity. Our self-calibrating design mitigates impacts of MRI uncertainties, ensuring robust evaluations pre- and post-intervention under varying MRI qualities. Extensively validated using a novel numerical phantom and 143 in vivo LA 3D MRIs of AF patients (pre- and post- ablation and serial post-ablation scans) and compared to 5 existing methods, our FSI index demonstrated strong correlations with traditional fibrosis measures and was able to quantify density and distribution pattern beyond entropy. FSI was up to 9 times more reliable and reproducible to MRI uncertainties (noise, segmentation, spatial resolution), highlighting its potential to improve cardiac MRI reliability and clinical utility.

Cardiovascular Magnetic Resonance 2024 Conference (CMR2024) convened in London, UK, from 24 to 26 January 2024 and brought together 2705 learners and renowned cardiac imaging professionals to discuss and learn about the latest advancements. Organized by the Society for Cardiovascular Magnetic Resonance (SCMR) and the European Association of Cardiovascular Imaging (EACVI), in collaboration with the European Society of Cardiovascular Radiology (ESCR), CMR2024 was the largest international cardiac magnetic resonance conference to date. This conference underscored the collaboration between cardiologists, radiologists, scientists, and technologists by bringing together three major societies-SCMR, EACVI, and ESCR. Innovative session formats like 'Shark Tank' and 'Workflow, Innovations & Patients' facilitated expert opinion and practical experiences sharing in a 'TED-talk style'. With over 1168 abstract submissions and 75% acceptance rate, the programme featured multiple Early Career Award sessions, oral scientific sessions, oral case sessions, and rapid-fire sessions, all categorized by topic. Highlights included patient- and physician-centred imaging sessions, sharing referring physicians' and patients' insights of incremental value of cardiovascular magnetic resonance (CMR) in patient's management. The programme offered invited lectures in eight parallel tracks with three plenary and two keynote speakers. In addition, the interactive workshops and panel discussions provided a platform for knowledge exchange, support, and collaboration. A great emphasis was placed on collaboration between radiologists, cardiologists, scientists, and technologists, showcasing an ideal cardiac imaging marriage as a model for enhanced patient care around the globe. The event also featured exhibitions of the latest CMR technology and software, offering attendees a glimpse into the future cardiac imaging. CMR2024 emerged as a remarkable scientific, educational, and networking event, inspiring attendees to learn and collaborate within the global CMR community., Competing Interests: Conflict of interest: None declared., (This article has been co–published with permission in the European Heart Journal – Cardiovascular Imaging and the Journal of Cardiovascular Magnetic Resonance. © The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.)

Atrial disease or myopathy is a growing concept in cardiovascular medicine, particularly in the context of atrial fibrillation, as well as amyloidosis and heart failure. Among cardiac imaging modalities, cardiovascular magnetic resonance (CMR) is particularly well suited for a comprehensive assessment of atrial myopathy, including tissue characterization and hemodynamics. The goal of this review article is to describe clinical applications and make recommendations on pulse sequences as well as imaging parameters to assess the left atrium and left atrial appendage. Furthermore, we aimed to create an overview of current and promising future emerging applications of left atrium-specific CMR pulse sequences focusing on both electrophysiologic (EP) and non-EP applications., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pluripotent stem cells provide a scalable approach to analyse molecular regulation of cell differentiation across developmental lineages. Here, we engineer barcoded induced pluripotent stem cells to generate an atlas of multilineage differentiation from pluripotency, encompassing an eight-day time course with modulation of WNT, BMP, and VEGF signalling pathways. Annotation of in vitro cell types with reference to in vivo development reveals diverse mesendoderm lineage cell types including lateral plate and paraxial mesoderm, neural crest, and primitive gut. Interrogation of temporal and signalling-specific gene expression in this atlas, evaluated against cell type-specific gene expression in human complex trait data highlights the WNT-inhibitor gene TMEM88 as a regulator of mesendodermal lineages influencing cardiovascular and anthropometric traits. Genetic TMEM88 loss of function models show impaired differentiation of endodermal and mesodermal derivatives in vitro and dysregulated arterial blood pressure in vivo. Together, this study provides an atlas of multilineage stem cell differentiation and analysis pipelines to dissect genetic determinants of mammalian developmental physiology., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: To use robotic visible-light optical coherence tomography (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration., Methods: Anterior segment imaging using a robotic vis-OCT to maintain perpendicular laser illumination aimed at SC was performed. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. SC areas and volumes were measured circumferentially., Results: Circumferential vis-OCT provided high-resolution imaging of the AHO pathways. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 µm2) and the least nasal (2727 ± 218 µm2; P = 0.018). After pilocarpine administration, the SC became larger (pilocarpine, 26.8 ± 5.0% vs. control, 8.9 ± 4.6% volume increase; P = 0.030). However, the pilocarpine alteration was also segmental, with a greater increase observed superior (pilocarpine, 31.6 ± 8.9% vs. control, 1.8 ± 5.7% volume increase; P = 0.023) and nasal (pilocarpine, 41.1 ± 15.3% vs. control, 13.9 ± 4.5% volume increase; P = 0.045)., Conclusions: Circumferential noninvasive imaging of the AHO pathways was done in vivo. Segmental SC anatomy was seen, consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was also observed. Segmental glaucoma drug response around the circumference of AHO pathways is an observation that may influence patient response to glaucoma treatments.

Background: While endovascular thrombectomy (EVT) has become standard of care for patients' acute ischemic stroke (AIS) due to large vessel occlusion (LVO), many patients still suffer profound neurological disability, also termed futile recanalization (FR). The BAND score, which incorporates baseline disability, age, stroke severity, and treatment time window, is derived as a simple tool for upfront prediction of FR prior to EVT. This study aims to externally validate the BAND score and to incorporate upfront imaging biomarkers into the prediction tool., Methods: Consecutive stroke thrombectomy patients with anterior circulation LVO who achieved successful recanalization (mTICI 2b or greater) were retrospectively identified at a single institution from 2019 to 2023. Clinical information, procedural details, and 90-day outcomes were recorded. The performance of the BAND score in predicting FR (90-day modified Rankin scale [mRS] >3) and loss of complete independence (LCID, 90-day mRS>2) was assessed. Then, Alberta stroke programme early CT score (ASPECTS) was added to create the PANDA score (pre-stroke disability, age, NIH stroke scale, delay from last known normal, and ASPECTS). The performance of PANDA to predict FR was assessed and compared with the original BAND score and also the widely validated THRIVE score., Results: 296 patients were included; 36.5 % experienced FR. BAND had areas under the receiver-operating curve (AUCs) of 0.72 and 0.74 for predicting FR and LCID, respectively (both p < 0.001). The new PANDA score had AUCs of 0.76 and 0.78 for predicting FR and LCID, respectively (both p < 0.001), and it outperformed both BAND and THRIVE (all p < 0.05). Of the 30 patients (11.2 %) with high PANDA scores (≥7), 24 patients (80.0 %) suffered FR and 26 (86.7 %) suffered LCID., Conclusion: This external validation study confirmed the adequate performance of BAND in predicting FR. The improved PANDA score performed better than the original BAND score and the widely validated THRIVE score., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis. Infection in macrophage-specific aryl hydrocarbon receptor (AhR) knockout mice revealed that AhR activation induced transcriptional reprogramming in macrophages and increased bacterial clearance and host survival. However, culture supernatants from multiple bacterial pathogens inhibited AhR activation in vitro. We showed that the secreted siderophore, enterobactin, inhibited AhR activation in vitro and increased sepsis mortality in vivo. By contrast, oral or systemic tryptophan supplementation increased survival. These findings show that sepsis survival depends upon the interplay between pathogen inhibition and the activation of AhR by a microbiota-derived metabolite., Competing Interests: Competing interests: The authors declare nocompeting interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Abstract: Occupational radiation dosimeters that return high readings cannot always be explained by circumstances in the workplace. For this experiment, a series of optically stimulated luminescence (OSL) dosimeters were brought to airports to estimate the radiation dose OSLs would receive should a worker accidentally bring their dosimeter with them during travel. The OSLs returned readings between 0.77 and 3.70 mSv. While factors such as scanning times, machine modality and model, flight duration, and elevation changes can all affect dosimeter readings, this small experiment provides a general range of dose readings to dosimeters to assist radiation safety program managers in quantifying true radiation dose from the workplace., (Copyright © 2025 Health Physics Society.)

Purpose: Aqueous humor inflow rate, a key parameter influencing aqueous humor dynamics, is typically measured by fluorophotometry. Analyzing fluorophotometric data depends, inter alia, on the volume of aqueous humor in the anterior chamber but not the posterior chamber. Previous fluorophotometric studies of the aqueous inflow rate in mice have assumed the ratio of anterior:posterior volumes in mice to be similar to those in humans. Our goal was to measure anterior and posterior chamber volumes in mice to facilitate better estimates of aqueous inflow rates., Methods: We used standard near-infrared (NIR) optical coherence tomography (OCT) and robotic visible-light OCT (vis-OCT) to visualize, reconstruct, and quantify the volumes of the anterior and posterior chambers of the mouse eye in vivo. We used histology and micro-computed tomography (CT) scans to validate relevant landmarks from ex vivo tissues and facilitate in vivo measurement., Results: Posterior chamber volume is 1.1 times the anterior chamber volume in BALB/cAnNCrl mice, that is, the anterior chamber constitutes about 47% of the total aqueous humor volume, which is very dissimilar to the situation in humans. Anterior chamber volumes in 2-month-old BALB/cAnNCrl and C57BL6/J mice were 1.55 ± 0.36 µL (n = 10) and 2.05 ± 0.25 µL (n = 10), respectively. This implies that previous studies likely overestimated the aqueous inflow rate by approximately twofold., Conclusions: It is necessary to reassess previously reported estimates of aqueous inflow rates and, thus, aqueous humor dynamics in the mouse. For example, we now estimate that only 0% to 15% of aqueous humor drains via the pressure-independent (unconventional) route, similar to that seen in humans and monkeys.

Introduction: Osteotomies are routinely incorporated in rhinoplasty, however, the influence of mass, velocity, kinetic energy (KE), and momentum (p) of the mallet on fracture patterns has not been studied., Methods: An experimental sledge guillotine setup was designed simulating a mallet strike with adjustable height and mass and 2 mm-thick Sawbone blocks. KE and p were calculated using KE = ½ mass × velocity 2 and p = mass × velocity formulas. Fracture lengths and angles were measured., Results: Ten groups with varying mallet masses and drop heights were tested with 10 bones per group. Fracture length positively correlated with KE (R = 0.542, p < 0.001) and p (R = 0.508, p < 0.001). Fracture angle also positively correlated with KE (R = 0.367, p < 0.001) and p (R = 0.329, p < 0.001). In groups with similar KE, osteotomies with higher p (heavier mallet with slower velocity) had greater fracture lengths (29.31 ± 0.68 vs. 27.68 ± 2.12 mm, p = 0.013) but similar fracture angles (p = 0.189). In groups with similar p, osteotomies with higher KE (lighter hammer with faster velocity) had significantly greater fracture lengths (28.28 ± 1.28 vs. 20.45 ± 12.20 mm, p = 0.041) and greater divergent fracture angles (3.13 ± 1.97° vs. 1.40 ± 1.36°, p = 0.031). Regression modeling of the relationship between KE and fracture lengths and angles demonstrated that cubic followed by logarithmic regression models had the best fits., Conclusion: Osteotomy fracture patterns positively correlated with the mallet's KE more so than its p, suggesting that the mallet's velocity has an increased impact effect than its mass. Clinically, a heavier mallet with a lower velocity will likely generate a smaller fracture length and fracture angle, indicating a more controlled and ideal fracture., Level of Evidence: NA Laryngoscope, 135:97-103, 2025., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Highly-undersampled, dynamic MRI reconstruction, particularly in multi-coil scenarios, is a challenging inverse problem. Unrolled networks achieve state-of-the-art performance in MRI reconstruction but suffer from long training times and extensive GPU memory cost., Methods: In this work, we propose a novel training strategy for IMplicit UNrolled NEtworks (IMUNNE) for highly-undersampled, multi-coil dynamic MRI reconstruction. It formulates the MRI reconstruction problem as an implicit fixed-point equation and leverages gradient approximation for backpropagation, enabling training of deep architectures with fixed memory cost. This study represents the first application of implicit network theory in the context of real-time cine MRI. The proposed method is evaluated using a prospectively undersampled, real-time cine dataset using radial k-space sampling, comprising balanced steady-state free precession (b-SSFP) readouts. Experiments include a hyperparameter search, head-to-head comparisons with a complex U-Net (CU-Net) and an alternating unrolled network (Alt-UN), and an analysis of robustness under noise perturbations; peak signal-to-noise ratio, structural similarity index, normalized root mean-square error, spatio-temporal entropic difference, and a blur metric were used., Results: IMUNNE produced significantly and slightly better image quality compared to CU-Net and Alt-UN, respectively. Compared with Alt-UN, IMUNNE significantly reduced training and inference times, making it a promising approach for highly-accelerated, multi-coil real-time cine MRI reconstruction., Conclusion: IMUNNE strategy successfully applies unrolled networks to image reconstruction of highly-accelerated, real-time radial cine MRI., Significance: Implicit training enables rapid, high-quality, and cost-effective CMR exams by reducing training and inference times and lowering memory cost associated with advanced reconstruction methods.

Deep learning-based image synthesis for medical imaging is currently an active research topic with various clinically relevant applications. Recently, methods allowing training with misaligned data have started to emerge, yet current solution lack robustness and cannot handle other corruptions in the dataset. In this work, we propose a solution to this problem for training synthesis network for datasets affected by mis-registration, artifacts, and deformations. Our proposed method consists of three key innovations: meta-learning inspired re-weighting scheme to directly decrease the influence of corrupted instances in a mini-batch by assigning lower weights in the loss function, non-local feature-based loss function, and joint training of image synthesis network together with spatial transformer (STN)-based registration networks with specially designed regularization. Efficacy of our method is validated in a controlled synthetic scenario, as well as public dataset with such corruptions. This work introduces a new framework that may be applicable to challenging scenarios and other more difficult datasets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Men and women have different cardiovascular responses to spaceflight; however, few studies have focused on direct comparisons between sexes. We investigated the mechanisms of aortic stiffening in socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) for 14 days. Pulse wave velocity (PWV) was greater in the aortic arch of females after HLU versus control females (n = 6-8). HLU had no effect on aortic PWV in males (n = 5-6). Aortic α smooth muscle actin, myosin, collagen, elastin, and collagen-to-elastin ratio were not different in rats of either sex following HLU. The levels of G protein-coupled estrogen receptor (GPER) were lower in the aorta of SD females exposed to HLU compared with female controls but were not altered in males. HLU females also had lower aortic PPARγ, increased oxidative stress markers, and diastolic dysfunction compared with control females. GPER agonist G1 prevented the increase in PWV and 8-hydroxy-2'-deoxyguanosine without altering PPARγ or p47phox in HLU females (n = 4 in each group) suggesting that lower GPER may contribute to arterial stiffening in the setting of simulated microgravity. This study highlights sex-specific vascular adaptations to the state of simulated microgravity., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Overall there is a lack of evidence on the accuracy and precision of phase-contrast (PC) MRI in patients with cardiac implantable electronic devices (CIEDs). The purpose of this study is to determine whether aortic velocity measurements are influenced by a CIED., Methods: We scanned 21 adult patients and 8 pediatric volunteers using clinical standard PC and real-time PC (rt-PC) sequences with and without a CIED generator taped on human subjects (below the left clavicle for adults and children; also on the abdomen for children) to mimic image artifacts. Peak and mean velocities above the aortic valve were calculated., Results: The Bland-Altman analyses on peak velocity measurements in pediatric subjects showed that both the accuracy and precision worsen as the distance between the CIED and aortic valve decreases (i.e., from abdomen to below the left clavicle). Specifically, both the bias and the coefficient of variation (CV) for both clinical PC and rt-PC increased from the abdominal position (clinical: bias = -1.1%, CV = 4.3%; rt-PC: bias = -0.3%, CV = 3.4%) to the clavicle position (clinical: bias = -4.0%, CV = 8.1%; rt-PC: bias = 8.2%, CV = 7.3%). A similar trend was observed for mean velocity. The mean difference in peak and mean velocity measurements between rt-PC with CIED (either position) and clinical standard PC with no CIED was within 7.5%. In adult patients, the mean difference between rt-PC with CIED and clinical standard PC with CIED in peak velocity was 6.9%, and the CV was 7.9%., Conclusion: This study demonstrates that aortic velocity measurements are influenced by CIED in both adult and pediatric subjects., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Studies in SIV-infected macaques show that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posit that optimized ART regimens designed to have robust penetration in tissue reservoirs and long-lasting antiviral activity may be advantageous for HIV or SIV remission. Here we treat macaques infected with RT-SHIV with oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir/rilpivirine without (n = 4) or with (n = 4) the immune activator vesatolimod after the initial onset of viremia. We document full suppression in all animals during treatment (4-12 months) and no virus rebound after treatment discontinuation (1.5-2 years of follow up) despite CD8 + T cell depletion. We show efficient multidrug penetration in virus reservoirs and persisting rilpivirine in plasma for 2 years after the last dose. Our results document a type of virus remission that is achieved through early treatment initiation and provision of ultra long-lasting antiviral activity that persists after treatment cessation., Competing Interests: Competing interests: J.G.G.-L., M.B.D., W.H., P.W., and W.S. are named in a US Patent Application (No. 18/002,494) entitled “Methods for achieving viral remission using long-acting antiretroviral agents”. The remaining authors declare no competing interests., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: This study examined adherence to clinical practice guidelines (CPGs) and U.S. Food and Drug Administration (FDA) medication labels when prescribing psychotropic medications to Medicaid-insured children with attention-deficit hyperactivity disorder (ADHD)., Methods: A retrospective analysis was conducted with 2016-2018 Medicaid claims data across 46 states for children with an ADHD diagnosis and at least one psychotropic medication prescription (N=1,236,068 children). Medications recommended for pediatric use were identified with CPGs from the American Academy of Child and Adolescent Psychiatry and the Florida Medicaid Drug Therapy Management Program for Behavioral Health., Results: Across 46 states, 86.7% of children received guideline-recommended and FDA-approved medications for the treatment of ADHD and comorbid mental disorders. Antidepressants, antihistamines, and second-generation antipsychotics that were not included in CPGs were prescribed for 23.4% of children., Conclusions: High adherence to CPGs and FDA medication labels for medications prescribed for ADHD was observed, suggesting the effectiveness of guidelines in driving evidence-based care., Competing Interests: Dr. Naylor is the psychiatric consultant to the Illinois Department of Children and Family Services (DCFS) Psychotropic Medication Consent Program and is paid via a contract between the University of Illinois Chicago and DCFS. The other authors report no financial relationships with commercial interests.

Neutrophils are crucial for defense against numerous infections, and their migration and activations are tightly regulated to prevent collateral tissue damage. We previously performed a neutrophil-specific miRNA overexpression screening and identified several microRNAs, including miR-375, as potent modulators for neutrophil activity. Overexpression of miR-375 decreases neutrophil motility and migration in zebrafish and human neutrophil-like cells. We screened the genes downregulated by miR-375 in zebrafish neutrophils and identified that Cathepsin B (Ctsba) is required for neutrophil motility and chemotaxis upon tail wounding and bacterial infection. Pharmacological inhibition or neutrophil-specific knockout of ctsba significantly decreased the neutrophil chemotaxis in zebrafish and survival upon systemic bacterial infection. Notably, Ctsba knockdown in human neutrophil-like cells also resulted in reduced chemotaxis. Inhibiting integrin receptor function using RGDS rescued the neutrophil migration defects and susceptibility to systemic infection in zebrafish with either miR-375 overexpression or ctsba knockout. Our results demonstrate that miR-375 and its target Ctsba modulate neutrophil activity during tissue injury and bacterial infection in vivo, providing novel insights into neutrophil biology and the overall inflammation process., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: The norms governing surgical training warrant a deeper understanding of students' experiences and interpretations of professionalism issues in their learning environment. However, there is scant empirical evidence to describe this process. To fill this gap, we analyzed students' perceptions related to professionalism, moral distress, and communication in the surgical clerkship, particularly regarding their clinical supervisors, whom we refer to as mentors., Design: We retrospectively evaluated written case vignettes and survey responses from medical students on their surgical clerkships regarding their experiences of cases which raised professionalism concerns. Vignettes and surveys were part of standard curricular exercises and analyzed using both qualitative and quantitative methods., Setting: Our study was conducted at a private academic medical college in the northeast with an affiliated institute of bioethics., Participants: Two-hundred forty-one third year medical students on their surgical clerkships participated through required curricular submissions of case vignettes and surveys., Results: Vignettes and surveys from all 241 students were collected and analyzed. Of these, 106 (43.9%) were identified by the students as relating to professionalism, whereas the research team identified 148 (61.4%) cases as such. Major subtypes of professionalism concerns were categorized as "not showing proper respect" (38.5%), bias (30.4%) and "failure to meet medical standards of care" (29.1%). In professionalism cases, only 27.7% of students would emulate their mentor, 19.7% shared concerns with the mentor, and 58.8% experienced moral distress, all significantly worse than in nonprofessionalism cases (p < 0.001)., Conclusions: With an abundance of professionalism concerns noted, students experienced high rates of moral distress and were unlikely to share concerns with clinical mentors who they generally did not wish to emulate. Attention should be paid to providing a formal curricular venue in which students can discuss their concerns, as untoward experiences in the learning environment risk harming their learning and professional identity development., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Affective symptoms (i.e., depression, anxiety, and apathy) are the most prevalent subsyndrome of neuropsychiatric symptoms (NPS) in preclinical dementia, such as amnestic mild cognitive impairment (aMCI), and remain a challenge to understand and treat. The distressing nature of these symptoms and complexity of their concurrence and interaction necessitates improved understanding of their underlying neural correlates. We analyzed the relationships between functional brain topology (i.e., the way the brain's functional network is organized to allow efficient communication between regions) and affective symptoms in aMCI using cross-sectional and longitudinal methods. The analyses demonstrated that increased clustering coefficient (CC) was related to lower baseline and greater decreases in affective symptoms, while higher participation coefficient (PC) was correlated with more severe baseline affective symptoms. These findings suggest that the brain losing the capacity to form segregated functional units may be related to prevalence and severity of affective symptoms seen in aMCI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Lipids and their bioactive metabolites, notably lysophosphatidylcholine (LPC), are increasingly important in ischemic stroke research. Reduced plasma LPC levels have been linked to stroke occurrence and poor outcomes, positioning LPC as a potential prognostic or diagnostic marker. Nonetheless, the connection between plasma LPC levels and stroke severity remains unclear. This study aimed to elucidate this relationship by examining plasma LPC levels in conjunction with brain LPC levels to provide a deeper understanding of the underlying mechanisms. Adult male Sprague-Dawley rats underwent transient middle cerebral artery occlusion and were randomly assigned to different groups (sham-operated, vehicle, LPC supplementation, or LPC inhibition). We measured multiple LPC species in the plasma and brain, alongside assessing sensorimotor dysfunction, cerebral perfusion, lesion volume, and markers of BBB damage, inflammation, apoptosis, and oxidative stress. Among five LPC species, plasma LPC(16:0) and LPC(18:1) showed strong correlations with sensorimotor dysfunction, lesion severity, and mechanistic biomarkers in the rat stroke model. Despite notable discrepancies between plasma and brain LPC levels, both were strongly linked to functional outcomes and mechanistic biomarkers, suggesting that LPC's prognostic value is retained extracranially. This study advances the understanding of LPC as a blood marker in ischemic stroke and highlights directions for future research to further elucidate its association with stroke severity, particularly through investigations in more clinically representative models.

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Purpose: To use robotic visible-light OCT (vis-OCT) to study circumferential segmental Schlemm's canal (SC) anatomy in mice after topical pilocarpine administration., Methods: Anterior segment imaging was performed using a vis-OCT sample arm attached to a 6-degree-of-freedom robotic arm to maintain normal (perpendicular) laser illumination aimed at SC around the limbus. Sixteen mice were studied for repeatability testing and to study aqueous humor outflow (AHO) pathway response to topical drug. Pharmaceutical-grade pilocarpine (1%; n = 5) or control artificial tears (n = 9) were given, and vis-OCT imaging was performed before and 15 minutes after drug application. After SC segmentation, SC areas and volumes were measured circumferentially in control- and drug-treated eyes., Results: Circumferential vis-OCT provided high-resolution imaging of the anterior segment and AHO pathways, including SC. Segmental SC anatomy was visualized with the average cross-sectional area greatest temporal (3971 ± 328 μm 2 ) and the least nasal (2727 ± 218 μm 2 ; p = 0.018). After pilocarpine administration, the iris became flatter, and SC became larger (pilocarpine: 26.8 ± 5.0% vs. control: 8.9 ± 4.6% volume increase; p = 0.030). However, the pilocarpine alteration was segmental as well, with a greater increase observed superior (pilocarpine: 31.6 ± 8.9% vs. control: 1.8 ± 5.7% volume increase; p = 0.023) and nasal (pilocarpine: 41.1 ± 15.3% vs. control: 13.9 ± 4.5% volume increase; p = 0.045)., Conclusion: High-resolution circumferential non-invasive imaging using AS-OCT of AHO pathways is possible in living animals with robotic control. Segmental SC anatomy was seen at baseline and was consistent with the known segmental nature of trabecular AHO. Segmental SC anatomical response to a muscarinic agonist was seen as well. Segmental glaucoma drug response around the circumference of AHO pathways is a novel observation that may explain the variable patient response to glaucoma treatments.

We herein report a fundamental mechanistic investigation into photochemical metal-nitrenoid generation and inner-sphere transposition reactivity using organometallic photoprecursors. By designing Cp*Ir(hydroxamate)(Ar) complexes, we induced photo-initiated ligand activation, allowing us to explore the amidative σ(Ir-aryl) migration reactivity. A combination of experimental mechanistic studies, femtosecond transient absorption spectroscopy, and density functional theory (DFT) calculations revealed that the metal-to-ligand charge transfer enables the σ(N-O) cleavage, followed by Ir-acylnitrenoid generation. The final inner-sphere σ(Ir-aryl) group migration results in a net amidative group transposition., (© 2024 Wiley-VCH GmbH.)