Complement C3 From Astrocytes Plays Significant Roles in Sustained Activation of Microglia and Cognitive Dysfunctions Triggered by Systemic Inflammation After Laparotomy in Adult Male Mice.

Aberrant activation of complement cascades plays an important role in the progress of neurological disorders. Complement C3, the central complement component, has been implicated in synaptic loss and cognitive impairment. Recent study has shown that wound injury-induced systemic inflammation can trigger the increase of C3 in the brain. Our previous studies have demonstrated that laparotomy-triggered systemic inflammation could induce neuroinflammation and cognitive dysfunctions. Furthermore, sustained activation of microglia was observed even 14 days after laparotomy, while most of cytokines had returned to basal levels rapidly at the earlier time point. Although we have demonstrated that anti-inflammatory intervention successfully attenuated cognitive dysfunction by preventing increase of cytokines and activation of microglia, how sustained activation of microglia and cognitive dysfunction occur is still a mystery. In this study, we investigated the role of C3 in mediating activation of microglia and cognitive dysfunction by using laparotomy in adult male mouse only as the experimental model of systemic inflammation and AAV9-C3shRNA. Our data observed that laparotomy induced neurotoxic reactive astrocytes with an increase of C3 in the hippocampus. Furthermore, inhibition of C3 by AAV9-C3shRNA prevented synaptic engulfment by microglia and attenuated cognitive dysfunctions after laparotomy. Inhibition of C3 did not modulate activation of astrocytes and expression of various cytokines. Current findings demonstrated that C3 plays significant roles in sustained activation of microglia and cognitive dysfunctions, which suggests that C3 is the valuable molecule target to attenuate in neurological conditions characterised by neuroinflammation and cognitive dysfunction.

Downregulation of the glucose transporter GLUT 1 in the cerebral microvasculature contributes to postoperative neurocognitive disorders in aged mice.

INTRODUCTION: Glucose transporter 1 (GLUT1) is essential for glucose transport into the brain and is predominantly expressed in the cerebral microvasculature. Downregulation of GLUT1 precedes the development of cognitive impairment in neurodegenerative conditions. Surgical trauma induces blood-brain barrier (BBB) disruption, neuroinflammation, neuronal mitochondria dysfunction, and acute cognitive impairment. We hypothesized that surgery reduces the expression of GLUT1 in the BBB that in turn disrupts its integrity and contributes to metabolic dysregulation in the brain that culminates in postoperative cognitive impairment. METHODOLOGY: Using an abdominal surgery model in aged WT mice, we assessed the perioperative changes in cognitive performance, tight junction proteins expression, GLUT1 expression, and the associated metabolic effects in the hippocampus. Thereafter, we evaluated the effects of these parameters in aged mice with conditional overexpression of GLUT1, and then again in aged mice with conditional overexpression of GLUT1 with or without prior exposure to the GLUT1 inhibitor ST-31. RESULTS: We showed a significant decline in cognitive performance, along with GLUT1 reduction and diminished glucose metabolism, especially in the ATP level in the postoperative mice compared with controls. Overexpression of GLUT1 expression alleviated postoperative cognitive decline and improved metabolic profiles, especially in adenosine, but did not directly restore ATP generation to control levels. GLUT1 inhibition ameliorated the postoperative beneficial effects of GLUT1 overexpression. CONCLUSIONS: Surgery-induced GLUT1 reduction significantly contributes to postoperative cognitive deficits in aged mice by affecting glucose metabolism in the brain. It indicates the potential of targeting GLUT1 to ameliorate perioperative neurocognitive disorders.

ChatGPT versus human in generating medical graduate exam multiple choice questions-A multinational prospective study (Hong Kong S.A.R., Singapore, Ireland, and the United Kingdom).

INTRODUCTION: Large language models, in particular ChatGPT, have showcased remarkable language processing capabilities. Given the substantial workload of university medical staff, this study aims to assess the quality of multiple-choice questions (MCQs) produced by ChatGPT for use in graduate medical examinations, compared to questions written by university professoriate staffs based on standard medical textbooks. METHODS: 50 MCQs were generated by ChatGPT with reference to two standard undergraduate medical textbooks (Harrison's, and Bailey & Love's). Another 50 MCQs were drafted by two university professoriate staff using the same medical textbooks. All 100 MCQ were individually numbered, randomized and sent to five independent international assessors for MCQ quality assessment using a standardized assessment score on five assessment domains, namely, appropriateness of the question, clarity and specificity, relevance, discriminative power of alternatives, and suitability for medical graduate examination. RESULTS: The total time required for ChatGPT to create the 50 questions was 20 minutes 25 seconds, while it took two human examiners a total of 211 minutes 33 seconds to draft the 50 questions. When a comparison of the mean score was made between the questions constructed by A.I. with those drafted by humans, only in the relevance domain that the A.I. was inferior to humans (A.I.: 7.56 +/- 0.94 vs human: 7.88 +/- 0.52; p = 0.04). There was no significant difference in question quality between questions drafted by A.I. versus humans, in the total assessment score as well as in other domains. Questions generated by A.I. yielded a wider range of scores, while those created by humans were consistent and within a narrower range. CONCLUSION: ChatGPT has the potential to generate comparable-quality MCQs for medical graduate examinations within a significantly shorter time.

Tension Pneumomediastinum and Coronary Artery Thrombosis Following a Motorcycle Accident: A Case Report.

INTRODUCTION: Tension pneumomediastinum and coronary artery thrombosis (CAT) secondary to blunt polytrauma are, rare yet have the potential for serious complication. CASE REPORT: A 40-year-old man presented to the emergency department following a motorcycle accident. He was found to have multiple orthopedic injuries, pneumothorax, and pneumomediastinum. An electrocardiogram showed myocardial infarction. He developed obstructive shock physiology that resolved with mediastinal percutaneous needle drainage. Subsequent coronary angiography revealed acute thrombosis of the left circumflex artery. CONCLUSION: This is a rare case of traumatic tension pneumomediastinum associated with coronary artery thrombosis requiring coronary stenting. Emergency physicians should be mindful of CAT in the setting of blunt chest injury.

An Adult Case of Adenovirus-Associated Acute Disseminated Encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is an autoimmune neurological disease that predominately affects pediatric population. Only a single fatal adult case of adenovirus-associated ADEM has previously been published by Qamar et al. in 2021. Here, we present an adult case of adenovirus-associated ADEM, which was diagnosed early in her clinical course. The patient was treated with the prompt initiation of steroids, intravenous immune globulin (IVIG), and plasmapheresis (PLEX), and the patient recovered fully. This case highlights the importance of early accurate diagnosis for other clinicians to treat adenovirus-associated ADEM in a timely fashion to prevent a potentially fatal outcome.

Transcatheter Left Atrial Appendage Exclusion: Preclinical and Early Clinical Results With the Laminar Device.

BACKGROUND: The Laminar device rotates and closes the left atrial appendage (LAA) using an integrated ball and lock that excludes and eliminates the LAA pouch. There is a low device surface area, minimizing the risk of peridevice leak (PDL) and device-related thrombus (DRT) formation. OBJECTIVES: This study evaluates the safety and efficacy of the Laminar LAA exclusion device in healthy animals and human subjects with nonvalvular atrial fibrillation at risk of ischemic stroke and systemic thromboembolism. METHODS: The preclinical study implanted the Laminar device into canine subjects that underwent transesophageal echocardiography (TEE) and fluoroscopic evaluation, followed by necropsy and histological assessment at 45 and 150-days post-implant. The early clinical study implanted the device in human subjects, followed to 12 months postimplantation. Procedural success was defined as device implantation in the intended location without residual LAA leak >5 mm as seen by TEE. Safety endpoints included freedom from stroke, systemic embolism, pericardial effusion, or tamponade, life-threatening/major bleeding, or death. RESULTS: The Laminar device was successfully implanted in 10 canines. In all animals at 45 days and 150 days, no PDL or DRT was found, and histological examination showed fully closed LAAs covered with neo-endocardium. The device was successfully implanted in 15 human subjects with no safety events out to 12 months postimplantation. All subjects had successful protocol-defined LAA closure without DRT at 45 days by TEE and computed tomography, which remained stable through 12 months' follow-up. CONCLUSIONS: The preclinical and early clinical results demonstrate a promising safety and efficacy profile for the Laminar LAA exclusion device.

Transcatheter Left Atrial Appendage Closure.

Atrial fibrillation is the most common arrhythmia worldwide, placing a large population at risk for potentially disabling ischemic strokes, yet an estimated 50% of eligible patients cannot tolerate or are contraindicated to receive oral anticoagulation. Within the last 15 years, transcatheter options for left atrial appendage closure (LAAC) have provided a valuable alternative to chronic oral anticoagulation for reducing risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. With newer generation devices such as Watchman FLX and Amulet gaining approval from the US Food and Drug Administration in recent years, several large clinical trials have demonstrated the safety and efficacy of transcatheter LAAC in a population intolerant to systemic anticoagulation. In this contemporary review, we discuss the indications for transcatheter LAAC and the evidence evaluating the use of various device therapies currently available or in development. We also examine current unmet challenges in intraprocedural imaging and controversies in postimplantation antithrombotic regimens. Several ongoing seminal trials are hoping to clarify the role of transcatheter LAAC as a safe, first-line option for all patients with nonvalvular atrial fibrillation.

ST36 acupoint injection with anisodamine for postoperative nausea and vomiting in female patients after bariatric surgery: a prospective, randomized controlled trial.

BACKGROUND: The use of multimodal pharmacological prophylactic regimes has decreased postoperative nausea and vomiting (PONV) in general but it still occurs in over 60% of female patients after bariatric surgery. This study aimed to evaluate the efficacy of ST36 acupoint injection with anisodamine in prevention of PONV among female patients after bariatric surgery. METHODS: Ninety patients undergoing laparoscopic sleeve gastrectomy were randomly allocated to anisodamine or control group at the ratio of 2:1. Anisodamine or normal saline was injected into Zusanli (ST36) bilaterally after induction of general anesthesia. The incidence and severity of PONV were assessed during the first 3 postoperative days and at 3 months. The quality of early recovery of anesthesia, gastrointestinal function, sleep quality, anxiety, depression, and complications were also evaluated. RESULTS: Baseline and perioperative characteristics were comparable between two groups. In the anisodamine group, 25 patients (42.4%) experienced vomiting within postoperative 24 h compared with 21 (72.4%) in the control group (relative risk 0.59; 95% confidence interval 0.40-0.85). Time to first rescue antiemetic was 6.5 h in anisodamine group, and 1.7 h in the control group (P = 0.011). Less rescue antiemetic was required during the first 24 h in the anisodamine group (P = 0.024). There were no differences in either postoperative nausea or other recovery characteristics. CONCLUSIONS: The addition of ST36 acupoint injection with anisodamine significantly reduced postoperative vomiting without affecting nausea in female patients with obesity undergoing laparoscopic sleeve gastrectomy.

The Impact of Surgery on Circulating Malignant Tumour Cells in Oral Squamous Cell Carcinoma.

IMPORTANCE: The extent to which surgical management of oral squamous cell carcinoma (OSCC) disseminates cancer is currently unknown. OBJECTIVE: To determine changes in numbers of malignant cells released into systemic circulation immediately following tumour removal and over the first seven post-operative days. DESIGN: An observational study from March 2019 to February 2021. SETTING: This study was undertaken at Queen Mary University Hospital, Hong Kong. PARTICIPANTS: Patients with biopsy-proven oral SCC were considered for eligibility. Patients under 18 years of age, pregnant or lactating women and those unable to understand the study details or unable to sign the consent form were excluded. Twenty-two patients were enrolled (12 male and 10 female) with mean age of 65.5 years. INTERVENTION: Primary tumour management was performed in accord with multi-disciplinary team agreement. Anaesthesia and post-operative care were unaltered and provided in accord with accepted clinical practice. MAIN OUTCOMES AND MEASURES: Three types of malignant cells detected in peripheral blood samples were enumerated and sub-typed based on the presence of chromosomal aneuploidy and immunohistochemical characteristics. To test the hypothesis that malignant cells are released by surgery, the numbers of single circulating tumour cells (CTCs), circulating tumour microemboli (CTM) and circulating endothelial cells (CTECs) were recorded pre-operatively, upon tumour removal and the second and seventh post-operative days. RESULTS: Of a potential 88 data collection points, specimens were not obtainable in 12 instances. Tumour removal resulted in a statistically significant increase in CTCs and a non-statistically significant rise in CTMs. CTCs, CTMs and CTECs were detected in the majority of patients up to the seventh post-operative day. Individual patients demonstrated striking increases in post-operative CTCs and CTECs numbers. CONCLUSIONS/RELEVANCE: Surgical management of OSCC has a significant impact on the systemic distribution of cancer cells. Malignant cells persisted post-operatively in a manner independent of recognised staging methods suggesting differences in tumour biology between individuals. Further investigation is warranted to determine whether circulating malignant cell enumeration can be used to refine risk stratification for patients with OSCC.

Protein kinase D3 promotes neutrophil migration during viral infection.

Protein kinase D (PKD) is a serine/threonine kinase family with three isoforms (PKD1-3) that are expressed in most cells and implicated in a wide array of signaling pathways, including cell growth, differentiation, transcription, secretion, polarization and actin turnover. Despite growing interest in PKD, relatively little is known about the role of PKD in immune responses. We recently published that inhibiting PKD limits proinflammatory cytokine secretion and leukocyte accumulation in mouse models of viral infection, and that PKD3 is highly expressed in the murine lung and immune cell populations. Here we focus on the immune-related phenotypes of PKD3 knockout mice. We report that PKD3 is necessary for maximal neutrophil accumulation in the lung following challenge with inhaled polyinosinic:polycytidylic acid, a double-stranded RNA, as well as following influenza A virus infection. Using reciprocal bone marrow chimeras, we found that PKD3 is required in the hematopoietic compartment for optimal neutrophil migration to the lung. Ex vivo transwell and chemokinesis assays confirmed that PKD3-/- neutrophils possess an intrinsic motility defect, partly because of reduced surface expression of CD18, which is critical for leukocyte migration. Finally, the peak of neutrophilia was significantly reduced in PKD3-/- mice after lethal influenza A virus infection. Together, these results demonstrate that PKD3 has an essential, and nonredundant, role in promoting neutrophil recruitment to the lung. A better understanding of the isoform-specific and cell type-specific activities of PKD has the potential to lead to novel therapeutics for respiratory illnesses.

Precise single-cell transcriptomic mapping of normal and leukemic cell states reveals unconventional lineage priming in acute myeloid leukemia.

Initial classification of acute leukemia involves the assignment of blasts to cell states within the hematopoietic hierarchy based on morphological and immunophenotypic features. Yet, these traditional classification approaches lack precision, especially at the level of immature blasts. Single-cell RNA-sequencing (scRNA-seq) enables precise determination of cell state using thousands of markers, thus providing an opportunity to re-examine present-day classification schemes of acute leukemia. Here, we developed a detailed reference map of human bone marrow hematopoiesis from 263,519 single-cell transcriptomes spanning 55 cellular states. Cell state annotations were benchmarked against purified cell populations, and in-depth characterization of gene expression programs underlying hematopoietic differentiation was undertaken. Projection of single-cell transcriptomes from 175 samples spanning acute myeloid leukemia (AML), mixed phenotype acute leukemia (MPAL), and acute erythroid leukemia (AEL) revealed 11 subtypes involving distinct stages of hematopoietic differentiation. These included AML subtypes with notable lymphoid or erythroid lineage priming, challenging traditional diagnostic boundaries between AML, MPAL, and AEL. Quantification of lineage priming in bulk patient cohorts revealed specific genetic alterations associated with this unconventional lineage priming. Integration of transcriptional and genetic information at the single-cell level revealed how genetic subclones can induce lineage restriction, differentiation blocks, or expansion of mature myeloid cells. Furthermore, we demonstrate that distinct cellular hierarchies can co-exist within individual patients, providing insight into AML evolution in response to varying selection pressures. Together, precise mapping of hematopoietic cell states can serve as a foundation for refining disease classification in acute leukemia and understanding response or resistance to emerging therapies.

Nonreciprocal vortex isolator via topology-selective stimulated Brillouin scattering.

Optical nonreciprocity, which breaks the symmetry between forward and backward propagating optical waves, has become vital in photonic systems and enables many key applications. So far, all the existing nonreciprocal systems are implemented for linearly or randomly polarized fundamental modes. Optical vortex modes, with wavefronts that spiral around the central axis of propagation, have been extensively studied over the past decades and offer an additional degree of freedom useful in many applications. Here, we report a light-driven nonreciprocal isolation system for optical vortex modes based on topology-selective stimulated Brillouin scattering (SBS) in chiral photonic crystal fiber. The device can be reconfigured as an amplifier or an isolator by adjusting the frequency of the control signal. The experimental results show vortex isolation of 22 decibels (dB), which is at the state of the art in fundamental mode isolators using SBS. This device may find applications in optical communications, fiber lasers, quantum information processing, and optical tweezers.

The role of PKC/PKR in aging, Alzheimer's disease, and perioperative neurocognitive disorders.

Background: The incidence of perioperative neurocognitive disorders (PNDs) is reportedly higher in older patients. Mitochondrial and synaptic dysfunctions have consistently been demonstrated in models of aging and neurodegenerative diseases; nonetheless, their role in PND is not well understood. Methods: The Morris water maze and elevated plus maze tests were used to assess the learning and memory abilities of both C57BL/6 and 3×Tg-AD mice of different ages (8 and 18 months). PND was induced by laparotomy in C57BL/6 mice and 3×Tg-AD mice (8 months old). Markers associated with neuroinflammation, mitochondrial function, synaptic function, and autophagy were assessed postoperatively. The roles of protein kinase C (PKC) and double-stranded RNA-dependent protein kinase (PKR) were further demonstrated by using PKC-sensitive inhibitor bisindolylmaleimide X (BIMX) or PKR-/- mice. Results: Significant cognitive impairment was accompanied by mitochondrial dysfunction and autophagy inactivation in both aged C57BL/6 and 3×Tg-AD mice. Laparotomy induced a significant neuroinflammatory response and synaptic protein loss in the hippocampus. Cognitive and neuropathological changes induced by aging or laparotomy were further exacerbated in 3×Tg-AD mice. Deficits in postoperative cognition, hippocampal mitochondria, autophagy, and synapse were significantly attenuated after pharmacological inhibition of PKC or genetic deletion of PKR. Conclusions: Our findings suggest similar pathogenic features in aging, Alzheimer's disease, and PND, including altered mitochondrial homeostasis and autophagy dysregulation. In addition, laparotomy may exacerbate cognitive deficits associated with distinct neuronal inflammation, mitochondrial dysfunction, and neuronal loss independent of genetic background. The dysregulation of PKC/PKR activity may participate in the pathogenesis of these neurodegenerative diseases.

Virtual ER, a Serious Game for Interprofessional Education to Enhance Teamwork in Medical and Nursing Undergraduates: Development and Evaluation Study.

BACKGROUND: Engaging students in interprofessional education for higher order thinking and collaborative problem-solving skills is challenging. This study reports the development of Virtual ER, a serious game played on a virtual platform, and how it can be an innovative way for delivering interprofessional education to medical and nursing undergraduates. OBJECTIVE: We report the development of a serious online game, Virtual ER, and evaluate its effect on teamwork enhancement and clinical competence. We also explore if Virtual ER can be an effective pedagogical tool to engage medical and nursing students with different learning styles. METHODS: Virtual ER is a custom-made, learning outcome-driven, case-based web app. We developed a game performance scoring system with specific mechanisms to enhance serious gaming elements. Sixty-two students were recruited from our medical and nursing programs. They played the games in teams of 4 or 5, followed by an instructor-led debriefing for concept consolidation. Teamwork attitudes, as measured by the Human Factors Attitude Survey, were compared before and after the game. Learning style was measured with a modified Honey and Mumford learning style questionnaire. RESULTS: Students were satisfied with Virtual ER (mean satisfaction score 5.44, SD 0.95, of a possible 7). Overall, Virtual ER enhanced teamwork attitude by 3.02 points (95% CI 1.15-4.88, P=.002). Students with higher scores as activists (estimate 9.09, 95% CI 5.17-13.02, P<.001) and pragmatists (estimate 5.69, 95% CI 1.18-10.20, P=.01) had a significantly higher degree of teamwork attitude enhancement, while students with higher scores as theorists and reflectors did not demonstrate significant changes. However, there was no difference in game performance scores between students with different learning styles. CONCLUSIONS: There was considerable teamwork enhancement after playing Virtual ER for interprofessional education, in particular for students who had activist or pragmatist learning styles. Serious online games have potential in interprofessional education for the development of 21st century life skills. Our findings also suggest that Virtual ER for interprofessional education delivery could be expanded locally and globally.

Leukocyte invasion of the brain after peripheral trauma in zebrafish (Danio rerio).

Despite well-known systemic immune reactions in peripheral trauma, little is known about their roles in posttraumatic neurological disorders, such as anxiety, sickness, and cognitive impairment. Leukocyte invasion of the brain, a common denominator of systemic inflammation, is involved in neurological disorders that occur in peripheral inflammatory diseases, whereas the influences of peripheral leukocytes on the brain after peripheral trauma remain largely unclear. In this study, we found that leukocytes, largely macrophages, transiently invaded the brain of zebrafish larvae after peripheral trauma through vasculature-independent migration, which was a part of the systemic inflammation and was mediated by interleukin-1b (il1b). Notably, myeloid cells in the brain that consist of microglia and invading macrophages were implicated in posttraumatic anxiety-like behaviors, such as hyperactivity (restlessness) and thigmotaxis (avoidance), while a reduction in systemic inflammation or myeloid cells can rescue these behaviors. In addition, invading leukocytes together with microglia were found to be responsible for the clearance of apoptotic cells in the brain; however, they also removed the nonapoptotic cells, which suggested that phagocytes have dual roles in the brain after peripheral trauma. More importantly, a category of conserved proteins between zebrafish and humans or rodents that has been featured in systemic inflammation and neurological disorders was determined in the zebrafish brain after peripheral trauma, which supported that zebrafish is a translational model of posttraumatic neurological disorders. These findings depicted leukocyte invasion of the brain during systemic inflammation after peripheral trauma and its influences on the brain through il1b-dependent mechanisms.

Sevoflurane Induces Neurotoxicity in the Animal Model with Alzheimer's Disease Neuropathology via Modulating Glutamate Transporter and Neuronal Apoptosis.

Perioperative neurocognitive disorders are frequently observed in postoperative patients and previous reports have shown that pre-existing mild cognitive impairment with accumulated neuropathology may be a risk factor. Sevoflurane is a general anesthetic agent which is commonly used in clinical practice. However, the effects of sevoflurane in postoperative subjects are still controversial, as both neurotoxic or neuroprotective effects were reported. The purpose of this study is to investigate the effects of sevoflurane in 3 × Tg mice, a specific animal model with pre-existing Alzheimer's disease neuropathology. 3 × Tg mice and wild-type mice were exposed to 2 h of sevoflurane respectively. Cognitive function, glutamate transporter expression, MAPK kinase pathways, and neuronal apoptosis were accessed on day 7 post-exposure. Our findings indicate that sevoflurane-induced cognitive deterioration in 3 × Tg mice, which was accompanied with the modulation of glutamate transporter, MAPK signaling, and neuronal apoptosis in the cortical and hippocampal regions. Meanwhile, no significant impact was observed in wild-type mice. Our results demonstrated that prolonged inhaled sevoflurane results in the exacerbation of neuronal and cognitive dysfunction which depends on the neuropathology background.

Prehabilitative resistance exercise reduces neuroinflammation and improves mitochondrial health in aged mice with perioperative neurocognitive disorders.

BACKGROUND: Postoperative neurocognitive dysfunction remains a significant problem in vulnerable groups such as the elderly. While experimental data regarding its possible pathogenic mechanisms accumulate, therapeutic options for this disorder are limited. In this study, we evaluated the neuroprotective effect of a period of preconditioning resistant training on aged mice undergoing abdominal surgery. Further, we examined the underlying mechanisms from the perspective of neuroinflammatory state and synaptic plasticity in the hippocampus. METHODS: 18-month-old C57BL/6N mice were trained for 5 weeks using a ladder-climbing protocol with progressively increasing weight loading. Preoperative baseline body parameters, cognitive performance and neuroinflammatory states were assessed and compared between sedentary and trained groups of 9-month-old and 18-month-old mice. To access the neuroprotective effect of resistance training on postoperative aged mice, both sedentary and trained mice were subjected to a laparotomy under 3% sevoflurane anesthesia. Cognitive performance on postoperative day 14, hippocampal neuroinflammation, mitochondrial dysfunction and synaptic plasticity were examined and compared during groups. RESULTS: 18-month-old mice have increased body weight, higher peripheral and central inflammatory status, reduction in muscle strength and cognitive performance compared with middle-aged 9-month-old mice, which were improved by resistance exercise. In the laparotomy group, prehabilitative resistant exercise improved cognitive performance and synaptic plasticity, reduced inflammatory factors and glial cells activation after surgery. Furthermore, resistance exercise activated hippocampal PGC-1α/BDNF/Akt/GSK-3ß signaling and improved mitochondrial biogenesis, as well as ameliorated mitochondrial dynamics in postoperative-aged mice. CONCLUSIONS: Resistance exercise reduced risk factors for perioperative neurocognitive disorders such as increased body weight, elevated inflammatory markers, and pre-existing cognitive impairment. Accordantly, preoperative resistance exercise improved surgery-induced adverse effects including cognitive impairment, synaptic deficit and neuroinflammation, possibly by facilitate mitochondrial health through the PGC1-a/BDNF pathway.

Imaging and Clinical Findings in a Series of Six Cases of Rare Primary Mediastinal Liposarcoma.

Primary mediastinal liposarcoma is a rare, fat-containing malignant lesion that can manifest incidentally with varied imaging appearances. The size and location within the mediastinum can vary among patients. Here, the authors describe the clinical presentation, radiographic characteristics, management, and prognosis in a series of six patients with primary mediastinal liposarcoma. The following case series suggests that even simple-appearing fatty intrathoracic lesions may lead to the development of malignant imaging features. Keywords: Conventional Radiography, CT, MR Imaging, PET/CT, Soft Tissues/Skin, Thorax, Mediastinum ©RSNA, 2022.

Cerebral Glutamate Regulation and Receptor Changes in Perioperative Neuroinflammation and Cognitive Dysfunction.

Glutamate is the major excitatory neurotransmitter in the central nervous system and is intricately linked to learning and memory. Its activity depends on the expression of AMPA and NMDA receptors and excitatory amino transporters on neurons and glial cells. Glutamate transporters prevent the excess accumulation of glutamate in synapses, which can lead to aberrant synaptic signaling, excitotoxicity, or cell death. Neuroinflammation can occur acutely after surgical trauma and contributes to the development of perioperative neurocognitive disorders, which are characterized by impairment in multiple cognitive domains. In this review, we aim to examine how glutamate handling and glutamatergic function are affected by neuroinflammation and their contribution to cognitive impairment. We will first summarize the current data regarding glutamate in neurotransmission, its receptors, and their regulation and trafficking. We will then examine the impact of inflammation on glutamate handling and neurotransmission, focusing on changes in glial cells and the effect of cytokines. Finally, we will discuss these changes in the context of perioperative neuroinflammation and the implications they have for perioperative neurocognitive disorders.

Medical teachers' experience of emergency remote teaching during the COVID-19 pandemic: a cross-institutional study.

BACKGROUND: The COVID-19 pandemic and the consequent social distancing measures caused unprecedented disruption for medical and healthcare education. This study examined medical teachers' experience with emergency remote teaching during the pandemic and their acceptance of online teaching after the pandemic. METHODS: In this sequential mixed methods study, online surveys were disseminated to teachers (n = 139) at two Asia-Pacific medical schools to evaluate their experience with emergency remote teaching during the pandemic. Subsequently, in-depth interviews were conducted with teachers from both institutions (n = 13). Each interviewee was classified into an adopter category based on Rogers' Diffusion of Innovations Theory. Interview transcripts were analyzed thematically, and the descriptive themes were mapped to broader themes partly based on the Technology Acceptance Model and these included: (i) perceived usefulness of online teaching, (ii) perceived ease of delivering online teaching, (iii) experience with institutional support and (iv) acceptance of online teaching after the pandemic. RESULTS: Our participants described accounts of successes with their emergency remote teaching and difficulties they experienced. In general, most participants found it difficult to deliver clinical skills teaching remotely and manage large groups of students in synchronous online classes. With regards to institutional support, teachers with lower technological literacy required just-in-time technical support, while teachers who were innovative in their online teaching practices found that IT support alone could not fully address their needs. It was also found that teachers' acceptance of online teaching after the pandemic was influenced by their belief about the usefulness of online teaching. CONCLUSIONS: This study demonstrated that our participants managed to adapt to emergency remote teaching during this pandemic, and it also identified a myriad of drivers and blockers to online teaching adoption for medical teachers. It highlights the need for institutes to better support their teaching staff with diverse needs in their online teaching.