Abbreviated MRI in the evaluation of dizziness: report turnaround times and impact on length of stay compared to CT, CTA, and conventional MRI.

PURPOSE: Neuroimaging is often used in the emergency department (ED) to evaluate for posterior circulation strokes in patients with dizziness, commonly with CT/CTA due to speed and availability. Although MRI offers more sensitive evaluation, it is less commonly used, in part due to slower turnaround times. We assess the potential for abbreviated MRI to improve reporting times and impact on length of stay (LOS) compared to conventional MRI (as well as CT/CTA) in the evaluation of acute dizziness. MATERIALS AND METHODS: We performed a retrospective analysis of length of stay via LASSO regression for patients presenting to the ED with dizziness and discharged directly from the ED over 4 years (1/1/2018-12/31/2021), controlling for numerous patient-level and logistical factors. We additionally assessed turnaround time between order and final report for various imaging modalities. RESULTS: 14,204 patients were included in our analysis. Turnaround time for abbreviated MRI was significantly lower than for conventional MRI (4.40 h vs. 6.14 h, p < 0.001) with decreased impact on LOS (0.58 h vs. 2.02 h). Abbreviated MRI studies had longer turnaround time (4.40 h vs. 1.41 h, p < 0.001) and was associated with greater impact on ED LOS than non-contrast CT head (0.58 h vs. 0.00 h), however there was no significant difference in turnaround time compared to CTA head and neck (4.40 h vs. 3.86 h, p = 0.06) with similar effect on LOS (0.58 h vs. 0.53 h). Ordering both CTA and conventional MRI was associated with a greater-than-linear increase in LOS (additional 0.37 h); the same trend was not seen combining CTA and abbreviated MRI (additional 0.00 h). CONCLUSIONS: In the acute settings where MRI is available, abbreviated MRI protocols may improve turnaround times and LOS compared to conventional MRI protocols. Since recent guidelines recommend MRI over CT in the evaluation of dizziness, implementation of abbreviated MRI protocols has the potential to facilitate rapid access to preferred imaging, while minimizing impact on ED workflows.

Disorders with Ophthalmic and Thoracic Involvement.

A variety of systemic conditions involve the thorax and the eyes. While subtle or nonspecific eye symptoms can be the initial clinical manifestation of some disorders, there can be additional manifestations in the thorax that lead to a specific diagnosis and affect patient outcomes. For instance, the initial clinical manifestation of Sjögren syndrome is dry eye or xerophthalmia; however, the presence of Sjögren lung disease represents a fourfold increase in mortality. Likewise, patients with acute sarcoidosis can initially present with pain and redness of the eye from uveitis in addition to fever and parotitis. Nearly 90% of patients with sarcoidosis have thoracic involvement, and the ophthalmologic symptoms can precede the thoracic symptoms by several years in some cases. Furthermore, a diagnosis made in one system can result in the screening of other organs as well as prompt genetic evaluation and examination of family members, such as in the setting of Marfan syndrome or Ehlers-Danlos syndrome. Multimodality imaging, particularly CT and MRI, plays a vital role in identification and characterization of these conditions. While it is helpful for ophthalmologists to be knowledgeable about these conditions and their associations so that they can order the pertinent radiologic studies, it is also important for radiologists to use the clues from ophthalmologic examination in addition to imaging findings to suggest a specific diagnosis. Systemic conditions with thoracic and ophthalmologic manifestations can be categorized as infectious, inflammatory, autoimmune, neoplastic, or hereditary in origin. The authors describe a spectrum of these conditions based on their underlying cause. ©RSNA, 2024.

Cost-Effectiveness of CT, CTA, MRI, and Specialized MRI for Evaluation of Patients Presenting to the Emergency Department With Dizziness.

BACKGROUND. Underlying stroke is often misdiagnosed in patients presenting with dizziness. Although such patients are usually ineligible for acute stroke treatment, accurate diagnosis may still improve outcomes through selection of patients for secondary prevention measures. OBJECTIVE. The purpose of our study was to investigate the cost-effectiveness of differing neuroimaging approaches in the evaluation of patients presenting to the emergency department (ED) with dizziness who are not candidates for acute intervention. METHODS. A Markov decision-analytic model was constructed from a health care system perspective for the evaluation of a patient presenting to the ED with dizziness. Four diagnostic strategies were compared: noncontrast head CT, head and neck CTA, conventional brain MRI, and specialized brain MRI (including multiplanar high-resolution DWI). Differing long-term costs and outcomes related to stroke detection and secondary prevention measures were compared. Cost-effectiveness was calculated in terms of lifetime expenditures in 2022 U.S. dollars for each quality-adjusted life year (QALY); deterministic and probabilistic sensitivity analyses were performed. RESULTS. Specialized MRI resulted in the highest QALYs and was the most cost-effective strategy with US$13,477 greater cost and 0.48 greater QALYs compared with noncontrast head CT. Conventional MRI had the next-highest health benefit, although was dominated by extension with incremental cost of US$6757 and 0.25 QALY; CTA was also dominated by extension, with incremental cost of US$3952 for 0.13 QALY. Non-contrast CT alone had the lowest utility among the four imaging choices. In the deterministic sensitivity analyses, specialized MRI remained the most cost-effective strategy. Conventional MRI was more cost-effective than CTA across a wide range of model parameters, with incremental cost-effectiveness remaining less than US$30,000/QALY. Probabilistic sensitivity analysis yielded similar results as found in the base-case analysis, with specialized MRI being more cost-effective than conventional MRI, which in turn was more cost-effective than CTA. CONCLUSION. The use of MRI in patients presenting to the ED with dizziness improves stroke detection and selection for subsequent preventive measures. MRI-based evaluation leads to lower long-term costs and higher cumulative QALYs. CLINICAL IMPACT. MRI, incorporating specialized protocols when available, is the preferred approach for evaluation of patients presenting to the ED with dizziness, to establish a stroke diagnosis and to select patients for secondary prevention measures.

Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir.

BACKGROUND: Entecavir (ETV) is a potent and safe antiviral agent for patients with chronic hepatitis B (CHB); however, some patients may exhibit suboptimal response or resistance to ETV. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate. AIM: To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV. METHODS: A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia [Hepatitis B virus (HBV) DNA ≥ 20 IU/mL] or partial virologic response (HBV DNA < 20 IU/mL, but detectable) were enrolled in the study. The patients were randomly assigned to either continue ETV (0.5 mg) daily or switch to TAF (25 mg) daily for 48 wk. The primary endpoint was the proportion of patients who achieved a virologic response (HBV DNA level < 20 IU/mL) at week 48. Secondary endpoints included changes in serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-HBe levels, and renal and bone safety parameters. RESULTS: At week 48, the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group (93.3% vs 66.7%, P = 0.012). The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group (-3.8 vs -2.4 Log10 IU/mL, P < 0.001). The rates of ALT normalization, HBeAg loss, HBeAg seroconversion, and HBsAg loss were not found to significantly differ between the two groups. None of the patients developed genotypic resistance to ETV or TAF. Both drugs were well tolerated, with no serious adverse events or discontinuations caused by adverse events. No significant changes were observed in the estimated glomerular filtration rate, serum creatinine level, or urine protein-to-creatinine ratio in either group. The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group (-0.8% vs -2.1%, P = 0.004; -0.6% vs -1.8%, P = 0.007, respectively). CONCLUSION: Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.

CT With CTA Versus MRI in Patients Presenting to the Emergency Department With Dizziness: Analysis Using Propensity Score Matching.

BACKGROUND. CT with CTA is widely used to exclude stroke in patients with dizziness, although MRI has higher sensitivity. OBJECTIVE. The purpose of this article was to compare patients presenting to the emergency department (ED) with dizziness who undergo CT with CTA alone versus those who undergo MRI in terms of stroke-related management and outcomes. METHODS. This retrospective study included 1917 patients (mean age, 59.5 years; 776 men, 1141 women) presenting to the ED with dizziness from January 1, 2018, to December 31, 2021. A first propensity score matching analysis incorporated demographic characteristics, medical history, findings from the review of systems, physical examination findings, and symptoms to construct matched groups of patients discharged from the ED after undergoing head CT with head and neck CTA alone and patients who underwent brain MRI (with or without CT and CTA). Outcomes were compared. A second analysis compared matched patients discharged after CT with CTA alone and patients who underwent specialized abbreviated MRI using multiplanar high-resolution DWI for increased sensitivity for posterior circulation stroke. Sensitivity analyses were performed involving MRI examinations performed as the first or only neuroimaging examination and involving alternative matching and imputation techniques. RESULTS. In the first analysis (406 patients per group), patients who underwent MRI, compared with patients who underwent CT with CTA alone, showed greater frequency of critical neuroimaging results (10.1% vs 4.7%, p = .005), change in secondary stroke prevention medication (9.6% vs 3.2%, p = .001), and subsequent echocardiography evaluation (6.4% vs 1.0%, p < .001). In the second analysis (100 patients per group), patients who underwent specialized abbreviated MRI, compared with patients who underwent CT with CTA alone, showed greater frequency of critical neuroimaging results (10.0% vs 2.0%, p = .04), change in secondary stroke prevention medication (14.0% vs 1.0%, p = .001), and subsequent echocardiography evaluation (12.0% vs 2.0%, p = .01) and lower frequency of 90-day ED readmissions (12.0% vs 28.0%, p = .008). Sensitivity analyses showed qualitatively similar findings. CONCLUSION. A proportion of patients discharged after CT with CTA alone may have benefitted from alternative or additional evaluation by MRI (including MRI using a specialized abbreviated protocol). CLINICAL IMPACT. Use of MRI may motivate clinically impactful management changes in patients presenting with dizziness.

Polyolefin-Based Separator with Interfacial Chemistry Regulation for Robust Potassium Metal Batteries.

Potassium metal batteries (KMBs) are ideal choices for high energy density storage system owing to the low electrochemical potential and low cost of K. However, the practical KMB applications suffer from intrinsically active K anode, which would bring serious safety concerns due to easier generation of dendrites. Herein, to explore a facile approach to tackle this issue, we propose to regulate K plating/stripping via interfacial chemistry engineering of commercial polyolefin-based separator using multiple functional units integrated in tailored metal organic framework. As a case study, the functional units of MIL-101(Cr) offer high elastic modulus, facilitate the dissociation of potassium salt, improve the K+ transfer number and homogenize the K+ flux at the electrode/electrolyte interface. Benefiting from these favorable features, uniform and stable K plating/stripping is realized with the regulated separator. Full battery assembled with the regulated separator showed ∼19.9 % higher discharge capacity than that with glass fiber separator at 20 mA g-1 and much better cycling stability at high rates. The generality of our approach is validated with KMBs using different cathodes and electrolytes. We envision that the strategy to suppress dendrite formation by commercial separator surface engineering using tailor-designed functional units can be extended to other metal/metal ion batteries.

Clinical criteria to exclude acute vascular pathology on CT angiogram in patients with dizziness.

BACKGROUND: Patients presenting to the emergency department (ED) with dizziness may be imaged via CTA head and neck to detect acute vascular pathology including large vessel occlusion. We identify commonly documented clinical variables which could delineate dizzy patients with near zero risk of acute vascular abnormality on CTA. METHODS: We performed a cross-sectional analysis of adult ED encounters with chief complaint of dizziness and CTA head and neck imaging at three EDs between 1/1/2014-12/31/2017. A decision rule was derived to exclude acute vascular pathology tested on a separate validation cohort; sensitivity analysis was performed using dizzy "stroke code" presentations. RESULTS: Testing, validation, and sensitivity analysis cohorts were composed of 1072, 357, and 81 cases with 41, 6, and 12 instances of acute vascular pathology respectively. The decision rule had the following features: no past medical history of stroke, arterial dissection, or transient ischemic attack (including unexplained aphasia, incoordination, or ataxia); no history of coronary artery disease, diabetes, migraines, current/long-term smoker, and current/long-term anti-coagulation or anti-platelet medication use. In the derivation phase, the rule had a sensitivity of 100% (95% CI: 0.91-1.00), specificity of 59% (95% CI: 0.56-0.62), and negative predictive value of 100% (95% CI: 0.99-1.00). In the validation phase, the rule had a sensitivity of 100% (95% CI: 0.61-1.00), specificity of 53% (95% CI: 0.48-0.58), and negative predictive value of 100% (95% CI: 0.98-1.00). The rule performed similarly on dizzy stroke codes and was more sensitive/predictive than all NIHSS cut-offs. CTAs for dizziness might be avoidable in 52% (95% CI: 0.47-0.57) of cases. CONCLUSIONS: A collection of clinical factors may be able to "exclude" acute vascular pathology in up to half of patients imaged by CTA for dizziness. These findings require further development and prospective validation, though could improve the evaluation of dizzy patients in the ED.

GPX4 deficiency-dependent phospholipid peroxidation drives motor deficits of ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by oxidative stress that triggers motor neurons loss in the brain and spinal cord. However, the mechanisms underlying the exact role of oxidative stress in ALS-associated neural degeneration are not definitively established. Oxidative stress-generated phospholipid peroxides are known to have extensive physiological and pathological consequences to tissues. Here, we discovered that the deficiency of glutathione peroxidase 4 (GPX4), an essential antioxidant peroxidase, led to the accumulation of phospholipid peroxides and resulted in a loss of motor neurons in spinal cords of ALS mice. Mutant human SOD1G93A transgenic mice were intrathecally injected with neuron-targeted adeno-associated virus (AAV) expressing GPX4 (GPX4-AAV) or phospholipid peroxidation inhibitor, ferrostatin-1. The results showed that impaired motor performance and neural loss induced by SOD1G93A toxicity in the lumbar spine were substantially alleviated by ferrostatin-1 treatment and AAV-mediated GPX4 delivery. In addition, the denervation of neuron-muscle junction and spinal atrophy in ALS mice were rescued by neural GPX4 overexpression, suggesting that GPX4 is essential for the motor neural maintenance and function. In comparison, conditional knockdown of Gpx4 in the spinal cords of Gpx4fl/fl mice triggered an obvious increase of phospholipid peroxides and the occurrence of ALS-like motor phenotype. Altogether, our findings underscore the importance of GPX4 in maintaining phospholipid redox homeostasis in the spinal cord and presents GPX4 as an attractive therapeutic target for ALS treatment.

BL-918, a small-molecule activator of ULK1, induces cytoprotective autophagy for amyotrophic lateral sclerosis therapy.

Amyotrophic lateral sclerosis (ALS) is one of the most common fatal neurodegenerative diseases in adults. ALS pathogenesis is associated with toxic SOD1 aggregates generated by mutant SOD1. Since autophagy is responsible for the clearance of toxic protein aggregates including SOD1 aggregates, autophagy induction has been considered as a potential strategy for treating ALS. Autophagic signaling is initiated by unc-51 like autophagy activating kinase 1 (ULK1) complex. We previously identified that BL-918 as a specific ULK1 activator, which exerted cytoprotective effect against Parkinson's disease in vitro and in vivo. In this study we investigated whether BL-918 exerted a therapeutic effect against ALS, and characterized its pharmacokinetic profile in rats. In hSODG93A-NSC34 cells, treatment with BL-918 (5, 10 µM) dose-dependently induced ULK1-dependent autophagy, and eliminated toxic SOD1 aggregates. In SODG93A mice, administration of BL-918 (40, 80 mg/kg, b.i.d., i.g.) dose-dependently prolonged lifespan and improved the motor function, and enhanced the clearance of SOD1 aggregates in spinal cord and cerebral cortex through inducing autophagy. In the pharmacokinetic study conducted in rats, we found BL-918 and its 2 metabolites (M8 and M10) present in spinal cord and brain; after intragastric and intravenous administration, BL-918 reached the highest blood concentration compared to M8 and M10. Collectively, ULK1 activator BL-918 displays a therapeutic potential on ALS through inducing cytoprotective autophagy. This study provides a further clue for autophagic dysfunction in ALS pathogenesis.

Magic Dr.T? Tuberculous brain lesions in an immunocompetent patient-A case report.

Tuberculomas in the form of multiple ring-enhancing brain lesions is an uncommon occurrence in immunocompetent patient. Central nervous system tuberculosis may manifest as meningitis, tuberculoma, or abscess and can even occur in patients with or without active respiratory tract infection. In the case of active infection, specific antibiotic combinations and dosing duration are required, and respiratory isolation/precautionary measures must be taken by the health care workers and members of the family. Most literature has reported Central nervous system tuberculosis in patients with immunosuppression such as from HIV infection or solid organ transplantation; however, in endemic areas, CNS tuberculoma should be a differential consideration even for immunocompetent patients presenting with ring enhancing lesion (s). Our case highlights the importance of maintaining this clinical suspicion. Early diagnosis and management of our patient helped prevent potentially serious neurological sequelae.

Scenarios to improve CT head utilization in the emergency department delineated by critical results reporting.

PURPOSE: Increasing use of advanced imaging in the emergency department (ED) has resulted in higher cost without better outcomes. Our goal was to evaluate the yield of CT head exams by scenario to guide efforts at improving patient selection. METHODS: We performed a retrospective study at an academic medical center over 4 years (1/1/2014-12/31/2017). The chief complaint, imaging order, and exam result text were obtained for all adult ED encounters. For the 50 most common chief complaints leading to CT head exams, the ratio of exams to total encounters and ratio of critical results to imaging studies were calculated. Significant difference in "yield" was assessed via binomial test. RESULTS: Over 708,145 adult ED encounters, 58,783 CT head exams were ordered, with an overall critical result yield of 8.0%. The three most common chief complaints had higher yield (p < 0.05): altered mental status (9.8%), fall (9.7%), and new headache (10.1%). Lower yield (p < 0.05) was found for 19 chief complaints: dizziness (6.2%), falls in patients > 65 years old (7.1%), syncope (5.3%), seizure with known epilepsy (4.8%), chest pain (3.7%), head injury (4.9%), headache re-evaluation (7.0%), alcohol intoxication (2.5%), fatigue (6.5%), headache-recurrent or in the setting of known migraines (5.2%), hypertension (4.4%), lethargy (5.8%), loss of consciousness (5.3%), migraine (3.2%), psychiatric evaluation (2.9%), near syncope (4.6%), drug problem (3.1%), symptomatically decreased blood sugar (3.2%), and suicidal (1.7%). CONCLUSION: Our study provides a priority list of low yield scenarios of CT head use for improvement of patient selection.

Head and Neck CTA Utilization: Analysis of Ordering Frequency and Nonroutine Results Communication, With Focus on the 50 Most Common Emergency Department Clinical Presentations.

BACKGROUND. Utilization of head and neck CTA in the emergency department (ED) has grown disproportionately to other neuroimaging examinations. OBJECTIVE. The purpose of this article was to characterize utilization of head and neck CTA in the ED, comparing utilization and frequency of nonroutine results communication among patients' chief concerns. METHODS. All adult ED visits for a single health care system from January 2014 to December 2017 were retrospectively reviewed. Variables recorded included chief concerns, whether head and neck CTA was performed, and, if so, whether the report documented nonroutine results communication. The 50 chief concerns resulting in the highest number of head and neck CTA examinations were identified. Frequencies of head and neck CTA ordering and of nonroutine results communication were calculated. A subset of reports documenting nonroutine communication were manually reviewed. RESULTS. Head and neck CTA was ordered in 2.5% (17,903) of 708,145 ED visits in 236,476 patients (mean age, 49.8 ± 20.5 [SD] years; 110,952 men, 125,521 women, 3 unknown sex). Head and neck CTA was ordered for 833 distinct chief concerns. Nonroutine results communication was documented for 17.6% (3155/17,903) of examinations. Among the 50 chief concerns associated with the highest number of examinations, frequency of ordering head and neck CTA ranged from less than 0.5% (five concerns) to 55.2% (stroke code), and frequency of nonroutine communication ranged from 5.6% (transient ischemic attack) to 67.5% (unresponsive). Chief concerns not among the 50 most common accounted for 50.0% (8956/17,903) of examinations; these exhibited a collective frequency of nonroutine communication of 4.8% (429/8956). Manual review of 11.1% (350/3155) of reports with a nonroutine communication indicated an acute finding related to the indication in 51.1%, nonemergent but potentially explanatory finding in 14.0%, incidental finding in 28.0%, and communication of negative results in 6.9%. CONCLUSION. Head and neck CTA is ordered in 2.5% of ED visits for a wide range of chief concerns. Frequencies of ordering and of nonroutine results communication are highly variable among chief concerns. Acute indication-related findings account for half of nonroutine radiologist communications. CLINICAL IMPACT. Insight into patterns regarding head and neck CTA ordering and nonroutine results may help optimize patient selection and radiologist communications in the ED setting.

Pilot MRI-based strategies to improve the detection of stroke in patients with dizziness/vertigo.

Posterior strokes are frequently misdiagnosed as they present with non-specific complaints such as dizziness/vertigo. Emergency department (ED) practice often relies on CT/CTA to "exclude" infarct in such patients, providing false reassurance due to lower sensitivity of CT (42%) for stroke in the posterior circulation. We describe a pilot at our institution using a specialized MRI protocol with 95% sensitivity for posterior stroke, which may be used in place of CT/CTA or conventional MRI for stroke evaluation. Further development of this approach may help reduce the high rate of missed posterior stroke in patients presenting with dizziness.

Blind spots on CT imaging of the head: Insights from 5 years of report addenda at a single institution.

BACKGROUND: Errors of detection ("misses") are the major source of error in radiology. There is sparse prior literature describing patterns of detection error on CT head imaging. PURPOSE: The objective of this study was to gain insight to areas on CT head imaging where radiologists are most likely to miss clinically relevant findings. METHODS: We performed a cross-sectional study of consecutive reports of CT imaging of the head at a single institution spanning 5/1/2013-5/1/2018 (5 years). Detection errors described in addenda were categorized according to anatomic location, type of pathology, and potential impact on management. Blind spots were defined by the most common sites of missed findings. RESULTS: A total of 165,943 reports for CT head imaging were obtained. Addenda were found in 1658 (~1%) of reports, of which 359 (21.7%) described errors of detection. Within the extracranial soft tissues (n = 73) the most common "misses" were at incidentally imaged parotid glands and the frontal scalp. Within osseous structures (n = 149), blind spots included the nasal and occipital bones. Vascular lesions (n = 47) which passed detection were most common at the distal MCA, carotid terminus and sigmoid sinus/jugular bulb. No predisposition was seen for anatomic subsites within the CSF space (n = 60) and brain parenchyma (n = 65). CONCLUSIONS: Consistent patterns of blind spots are revealed. Radiologic teaching and search patterns to account for these sites of error may accelerate trainee competence and improve accuracy in the practice of radiology.

Novel insights into stress-induced susceptibility to influenza: corticosterone impacts interferon-ß responses by Mfn2-mediated ubiquitin degradation of MAVS.

Although stress has been known to increase the susceptibility of pathogen infection, the underlying mechanism remains elusive. In this study, we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus (H1N1) and obviously aggravated lung inflammation. Corticosterone (CORT), a main type of glucocorticoids in rodents, was secreted in the plasma of stressed mice. We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling (MAVS) protein-transduced IFN-ß production without affecting its mRNA level, while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice. Mechanistically, the effect of CORT was mediated by proteasome-dependent degradation of MAVS, thereby resulting in the impediment of MAVS-transduced IFN-ß generation in vivo and in vitro. Furthermore, RNA-seq assay results indicated the involvement of Mitofusin 2 (Mfn2) in this process. Gain- and loss-of-function experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS. Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2 (HR1), MAVS (C-terminal/TM) and SYVN1 (TM). Collectively, our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a 'fine tuning' of antiviral innate immunity in response to influenza infection under stress.

New insights into the effects of caffeine on adult hippocampal neurogenesis in stressed mice: Inhibition of CORT-induced microglia activation.

Chronic stress-evoked depression has been implied to associate with the decline of adult hippocampal neurogenesis. Caffeine has been known to combat stress-evoked depression. Herein, we aim to investigate whether the protective effect of caffeine on depression is related with improving adult hippocampus neurogenesis and explore the mechanisms. Mouse chronic water immersion restraint stress (CWIRS) model, corticosterone (CORT)-established cell stress model, a coculture system containing CORT-treated BV-2 cells and hippocampal neural stem cells (NSCs) were utilized. Results showed that CWIRS caused obvious depressive-like disorders, abnormal 5-HT signaling, and elevated-plasma CORT levels. Notably, microglia activation-evoked brain inflammation and inhibited neurogenesis were also observed in the hippocampus of stressed mice. In comparison, intragastric administration of caffeine (10 and 20 mg/kg, 28 days) significantly reverted CWIRS-induced depressive behaviors, neurogenesis recession and microglia activation in the hippocampus. Further evidences from both in vivo and in vitro mechanistic experiments demonstrated that caffeine treatment significantly suppressed microglia activation via the A2AR/MEK/ERK/NF-κB signaling pathway. The results suggested that CORT-induced microglia activation contributes to stress-mediated neurogenesis recession. The antidepression effect of caffeine was associated with unlocking microglia activation-induced neurogenesis inhibition.