Aggravating Pollution of Emerging Aryl Organophosphate Esters in Urban Estuarine Sediments of South China.

Emerging aryl organophosphate esters (aryl-OPEs) have been employed as substitutes for organohalogen flame retardants in recent years; however, their environmental occurrence and associated impacts in urban estuarine sediments have not been adequately investigated, impeding regulatory decision-making. Herein, field-based investigations and modeling based on surface sediment and sediment core analysis were employed to uncover the historical pollution and current environmental impacts of aryl-OPEs in the Pearl River Estuary, South China. Our results revealed a substantial increase in aryl-OPE emission, particularly emerging aryl-OPEs, through sediment transport to the estuary since the 2000s. The emerging aryl-OPEs comprised 83% of the total annual input in the past decade, with an average annual input of 155,000 g. Additionally, the emerging-to-traditional aryl-OPE concentration ratios increased with decreasing distance from the shore, peaking in the highly urbanized riverine outlets. These findings indicate that inventories of emerging aryl-OPEs are likely increasing in estuarine sediments and their emissions are surpassing those of traditional aryl-OPEs. Our risk-based priority screening approach indicates that some emerging aryl-OPEs, particularly bisphenol A bis(diphenyl phosphate), can pose a higher environmental risk than traditional aryl-OPEs in estuarine sediments. Overall, our study highlights the importance of recognizing the environmental impacts of emerging aryl-OPEs.

Severe flood modulates the sources and age of dissolved organic carbon in the Yangtze River Estuary.

Floods in global large rivers modulate the transport of dissolved organic carbon (DOC) and estuarine hydrological characteristics significantly. This study investigated the impact of a severe flood on the sources and age of DOC in the Yangtze River Estuary (YRE) in 2020. Comparing the flood period in 2020 to the non-flood period in 2017, we found that the flood enhanced the transport of young DOC to the East China Sea (ECS), resulting in significantly enriched Δ14C-DOC values. During the flood period, the proportion of modern terrestrial organic carbon (OC) was significantly higher compared to the non-flood period. Conversely, the proportion of pre-aged sediment OC was significantly lower during the flood period. The high turbidity associated with the flood facilitated rapid transformation and mineralization of sedimentary and fresh terrestrial OC, modifying the sources of DOC. The flux of modern terrestrial OC transported to the ECS during the flood period was 1.58 times higher than that of the non-flood period. These findings suggest that floods can modulate the sources and decrease the age of DOC, potentially leading to increased greenhouse gas emissions. Further research is needed to understand the long-term impacts of floods on DOC dynamics in global estuaries.

Revisiting the predictive role of truncal-type occlusion sign for acute large vessel stroke treated by endovascular thrombectomy: A scoping review.

Background and purpose The truncal type occlusion (TTO) sign observed during endovascular thrombectomy (EVT) is thought to predict the etiology and prognosis of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, the interpretation of the present results and the clinical utility of this sign needs further investigation. This scoping meta-review aimed to assess the predictive value of the TTO sign, thus identifying methodological limitations in current study designs. Methods Studies published up to January 2023 were identified by systematically searching PubMed, Embase, and Web of Science. A meta-analysis was performed to quantitatively synthesize the evidence on the predictive value of the TTO sign. An 8-point scale was introduced to narratively summarize the current evidence level and methodological quality of included studies. Results We included 10 studies in this review. For the prediction of intracranial atherosclerotic stenosis, the sensitivity, specificity, PLR and NLR of the TTO sign were 0.73, 0.87, 5.5 and 0.31, respectively (all p<0.05). For recanalization failure after primary thrombectomy, the sensitivity, specificity, PLR and NLR were 0.44, 0.91, 4.9 and 0.61, respectively (all p<0.05). The strength of evidence was low due to the methodological limitations and lack of adjustment for potential confounders. Conclusion The predictive values of the TTO sign for the etiology of LVO-AIS was considerable but seemed limited for current interpretation. Several confounders could influence the determination and predictive value of the TTO sign, requiring methodological adjustments in future research. Endovascular practitioners encountering this sign during thrombectomy should draw specific attention to stroke etiology, thus promoting timely adjustment of intra- and postprocedural strategies.

The Effect of Virtual Reality Training on Anticipatory Postural Adjustments in Patients with Chronic Nonspecific Low Back Pain: A Preliminary Study.

Objectives: This study is aimed at exploring the effects of virtual reality (VR) training on postural control, measured by anticipatory and compensatory postural adjustments (APAs and CPAs, respectively), in patients with chronic nonspecific low back pain (CNLBP) and the potential neuromuscular mechanism of VR training. Methods: Thirty-four patients were recruited and randomly assigned to the VR group (n = 11), the motor control exercise group (MCE, n = 12) and the control group (CG, n = 11). The VR group received VR training using Kinect Xbox 360 systems and magnetic therapy. Besides magnetic therapy, the participants in the MCE group performed real-time ultrasound-guided abdominal drawing-in maneuver (ADIM) and four-point kneeling exercise. The CG only received magnetic therapy. Surface muscle electromyography (sEMG) was used to record the muscle activities of transverse abdominis (TrA), multifidus (MF), lateral gastrocnemius (LG), and tibialis anterior (TA) during ball-hitting tasks. The muscle activation time and integrals of the electromyography activities (IEMGs) during the APA and CPA stages were calculated and used in the data analysis. The visual analogue scale (VAS) and Oswestry dysfunction index (ODI) scores were also recorded. Results: A significant interaction effect of time × group was observed on the activation time of TrA (p = 0.018) and MF (p = 0.037). The post-intervention activation time of the TrA was earlier in the VR group (p = 0.029). In contrast, the post-intervention activation time of the MF was significantly delayed in the VR group (p = 0.001). The IEMGs of TrA (p = 0.002) and TA (p = 0.007) during CPA1 significantly decreased only in the VR group after the intervention. The VAS scores of three group participants showed significant decreases after intervention (p < 0.001). Conclusions: Patients with CNLBP showed reciprocal muscle activation patterns of the TrA and MF muscles after VR training. VR training may be a potential intervention for enhancing the APAs of the patients with CNLBP.

Comparison of the Diagnostic Performances of Ultrasound, High-Resolution Magnetic Resonance Imaging, and Positron Emission Tomography/Computed Tomography in a Rabbit Carotid Vulnerable Plaque Atherosclerosis Model.

OBJECTIVES: Our study aimed to evaluate the diagnostic performances of 3 routine examination methods for cerebrovascular disease in a rabbit carotid artery atherosclerosis model. METHODS: A total of 12 New Zealand rabbits were included: 4 in a control group and 8 in an experimental group. A clinically relevant atherosclerosis rabbit model was induced by left common carotid artery ligation and a 12-week high-fat diet. Atherosclerosis was further confirmed by a histopathologic analysis. Then carotid ultrasound (US) imaging, high-resolution magnetic resonance imaging (HRMRI), and positron emission tomography (PET)/computed tomography (CT) were performed on this model to evaluate the diagnostic performances. RESULTS: Carotid US showed plaque formation in the left common carotid artery and little plaque in the right common carotid artery in the experimental group. In addition, HRMRI showed stenosis formation in the left common carotid artery in the experimental group. At the horizontal level, plaques were found in the left common carotid artery, and no plaques were found in the right common carotid artery in the experimental group. Also, PET/CT showed local hypermetabolism and vulnerable plaques in the left common carotid artery of the experimental group, whereas no hypermetabolism was found in the right common carotid artery of the experimental group. Moreover, the soft plaques detected by carotid US were different from the vulnerable plaques detected by PET/CT. The unstable plaques on HRMRI were the same as the hypermetabolic vulnerable plaques on PET/CT. CONCLUSIONS: High-resolution MRI is recommended for the evaluation of neck and intracranial vascular stenosis and plaque properties in patients with stroke.

Inhibition of P53/miR-34a improves diabetic endothelial dysfunction via activation of SIRT1.

Endothelial dysfunction contributes to diabetic macrovascular complications, resulting in high mortality. Recent findings demonstrate a pathogenic role of P53 in endothelial dysfunction, encouraging the investigation of the effect of P53 inhibition on diabetic endothelial dysfunction. Thus, high glucose (HG)-treated endothelial cells (ECs) were subjected to pifithrin-α (PFT-α)-a specific inhibitor of P53, or P53-small interfering RNA (siRNA), both of which attenuated the HG-induced endothelial inflammation and oxidative stress. Moreover, inhibition of P53 by PFT-α or P53-siRNA prohibited P53 acetylation, decreased microRNA-34a (miR-34a) level, leading to a dramatic increase in sirtuin 1 (SIRT1) protein level. Interestingly, the miR-34a inhibitor (miR-34a-I) and PFT-α increased SIRT1 protein level and alleviated the HG-induced endothelial inflammation and oxidative stress to a similar extent; however, these effects of PFT-α were completely abrogated by the miR-34a mimic. In addition, SIRT1 inhibition by EX-527 or Sirt1-siRNA completely abolished miR-34a-I's protection against HG-induced endothelial inflammation and oxidative stress. Furthermore, in the aortas of streptozotocin-induced diabetic mice, both PFT-α and miR-34a-I rescued the inflammation, oxidative stress and endothelial dysfunction caused by hyperglycaemia. Hence, the present study has uncovered a P53/miR-34a/SIRT1 pathway that leads to endothelial dysfunction, suggesting that P53/miR-34a inhibition could be a viable strategy in the management of diabetic macrovascular diseases.

Multiple antenna placement in microwave ablation assisted by a three-dimensional fusion image navigation system for hepatocellular carcinoma.

PURPOSE: This study was conducted to compare a three-dimensional (3D) fusion image navigation system (FINS) with ultrasound (US) for guiding percutaneous microwave ablation (PMWA) for treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This is a retrospective, non-randomized, comparative study. Our team developed a 3D FINS and used it to guide PMWAs for HCCs in 19 patients (3D group) and compared the results to those of 24 PMWAs guided by US (US group). The complete ablation rate of the first session, the local tumor progression (LTP), intrahepatic recurrence and disease-free survival were compared between the groups. RESULTS: The 3D FINS was successfully applied in all 19 patients. The mean size of HCCs was 4.14 cm ±0.95 in 3D the group and 4.07 cm ±0.91 in the US group. Major complications were identified at 5.3% in the 3D group and 4.2% in the US group (p = .865). Average time of image fusion was 404.53 ± 161.84 s. There were more antenna insertions in the 3D group (3.68 ± 1.57) than in the US group (2.71 ± 1.12) (p = .02). The complete ablation rate of the first session was higher in the 3D group (94.7%) than in the US group (62.5%) (p = .034). The mean follow-up period was 11.4 months ±4.9 in the 3D group and 9.8 months ±5.5 in the US group. There were no significant differences in technique efficacy rate and LTP rate between the two groups. CONCLUSIONS: The 3D FINS could be a safe, feasible and effective technique for guiding PMWA of HCC, which could help an operator improve the complete ablation rate of the first session.

Activin A/Smads signaling pathway negatively regulates Oxygen Glucose Deprivation-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.

Activin A (Act A), a member of the transforming growth factor-beta (TGF-ß), reduces neuronal apoptosis during cerebral ischemia through Act A/Smads signaling pathway. However, little is known about the effect of Act A/Smads pathway on autophagy in neurons. Here, we found that oxygen-glucose deprivation (OGD)-induced autophagy was suppressed by exogenous Act A in a concentration-dependent manner and enhanced by Act A/Smads pathway inhibitor (ActRIIA-Ab) in neuronal PC12 cells. These results indicate that Act A/Smads pathway negatively regulates autophagy in OGD-treated PC12 cells. In addition, we found that c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways are involved in the OGD-induced autophagy. The activation of JNK and p38 MAPK pathways in OGD-treated PC12 cells was suppressed by exogenous Act A and enhanced by ActRIIA-Ab. Together, our results suggest that Act A/Smads signaling pathway negatively regulates OGD-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.

Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop.

Activin A (Act A), a member of transforming growth factor-ß superfamily, plays a neuroprotective role in multiple neurological diseases through Act A/Smads signal activation. Traditionally, the up-regulation of Act A gene and extracellular Act A accumulation show the signal activation as a linear pathway. However, one of our discoveries indicated that Act A could lead a loop signaling in ischemic injury. To clarify the characteristic of this loop signaling in a non-pathological state, we up-regulated the expression of Act A, monitored extracellular Act A accumulation and examined the activity of Act A signaling, which was quantified by the expression of phosphorylated Smad3 and the fluorescence intensity of Smad4 in nuclei. The results demonstrated a noncanonical Act A signal loop with self-amplifying property in PC12 cells. Further, it showed self-limiting behavior due to temporary activation and spontaneous attenuation. This periodic behavior of Act A signal loop was found to be regulated by the level of Smad anchor for receptor activation (SARA). Moreover, increased activity of Act A signal loop could promote PC12 cell proliferation and enhance the survival rate of cells to Oxygen-Glucose Deprivation. These practical discoveries will bring new insight on the functional outcome of Act A signaling in neurological diseases by the further understanding: loop signaling.

Angiographic Pattern of M1 Stenosis Predicts Territorial Stroke in Patients Receiving Aggressive Medication without Stenting.

OBJECTIVE: To evaluate the relationship between different angiographic patterns of middle cerebral artery M1 segment stenosis and related territorial stroke in patients receiving aggressive medical treatment without stenting. METHODS: We retrospectively reviewed our patient registry database to identify ICAS patients diagnosed by digital subtraction angiography between January 2017 and December 2020 and identified 3 different angiographic patterns (normal, shift, and dilation) in 124 patients with M1 stenosis. The association between these patterns and recurrent ischemic stroke in the M1 territory was analyzed. RESULTS: The rates of recurrent M1 territorial stroke and transient ischemic attack in the normal group, shift group, dilation group and shift-dilation group were 34.5%, 35.0%, 78.3%, and 44.4% respectively. In patients with the shift pattern, the rate of recurrent stroke is significantly higher at a deflection angle ≥9.32° than at a deflection angle <9.32°(P < 0.05). In patients with dilation pattern, the rate of recurrent stroke is significantly higher than patients with non-dilation pattern (72.3% vs. 36.8%, P < 0.05). CONCLUSIONS: Angiographic patterns of M1 stenosis may predict recurrent territorial strokes, thus providing a surrogate marker to identify high-risk patients for potential endovascular treatment.

Revisiting the role of TEG-PM in stroke prevention by drug selection for mono-antiplatelet medication following dual-antiplatelet treatment.

BACKGROUNDS: Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for minor strokes or TIAs has been demonstrated in several RCTs. Whether drug selection for mono-antiplatelet therapy (MAPT) following DAPT may influence stroke recurrence has not been clarified, especially for patients with intracranial atherosclerosis stenosis (ICAS). The Thrombelastography Platelet Mapping (TEG-PM) assay claimed to be capable of monitoring platelet function secondary to antiplatelet therapy. PURPOSE: The aim of this study was to investigate the preventive role of TEG-PM in individualized drug selection for MAPT following DAPT in patients with minor stroke or TIA. METHODS: We retrospectively reviewed our patient database to identify individuals with minor stroke or TIA between February 2019 and July 2022. Patients were divided into ICAS and non-ICAS groups, and the efficacy and safety of TEG-PM-guided MAPT for stroke prevention after minor stroke or TIA were investigated in each group. RESULTS: ICAS patients with TEG-PM-guided MAPT had lower rates of recurrent stroke than patients without TEG-PM guidance during a mean follow-up period of 18.1 months (6.3% vs 15.2%; p = 0.04). Patients without ICAS also tended to benefit from TEG-PM-guided MAPT with lower rates of stroke recurrence (2.6% vs 8.7%; p = 0.02). No difference in the safety outcome of any bleeding events was observed in patients with TEG-PM-guided MAPT and those without (ICAS group, 2.1% vs 3.0%; p = 0.68; non-ICAS group, 1.3% vs 2.3%; p = 0.79). CONCLUSION: The TEG-PM could be a tangible preprocessing in drug selection for MAPT following DAPT in patients with minor strokes or TIAs, especially for those with non-stented ICASs.

Seasonal changes of dissolved organic matter chemistry and its linkage with greenhouse gas emissions in saltmarsh surface water and porewater interactions.

Dissolved organic matter (DOM) is one of the largest reactive reservoirs of carbon on earth. Saltmarshes play an essential role in shaping the fate of DOM and greenhouse gas (GHG) production in surface water and groundwater interactions in coastal areas. However, the coupling mechanism between DOM and GHG production is poorly understood. In this study, DOM in both surface water and porewater were analyzed by 3D excitation-emission-matrix spectroscopy under different seasonal and tidal conditions in a saltmarsh. Protein-like DOM was likely to produce CH4, while humic-like DOM tended to produce CO2. CH4 concentration was highly enriched in porewater because increasing fresh groundwater flow introduced small-sized protein-like DOM. Based on the mass balance model, >98.5% of CH4 was oxidated to CO2 in sediment-water interface. The degradation of sediment-derived DOC (especially humic-like DOM) contributes ∼80% of the total amount of CO2 in surface water. Both hydrodynamics and chemical reactions are suggested to influence greenhouse gas (GHG) emissions. Hydrodynamics (e.g., tidal pumping) are controlling factors in short timescales (hourly/weekly) while chemical reactions become crucial in influencing DOM chemistry and related degradation rate on seasonal scales. These findings emphasize the importance of the coupling mechanism at different time scales between DOM characteristics and GHG emissions in saltmarshes.

Drawing time-density curve with Fiji/ImageJ: An alternative approach for parametric coding of cerebral digital subtraction angiography.

BACKGROUND: Quantitative spatiotemporal analysis of digital subtraction angiography could support clinical decision making for the management of cerebral vascular disease. However, there is a lack of free and user-friendly applications. The objective of our study is to devise a free and simple solution for parametric coding of digital subtraction angiography. NEW METHOD: By driving the time-density curves in the region of interest, the digital subtraction angiography images were color-coded and quantitatively analyzed using fully open-source and free software (Fiji/ImageJ). The similarity factor (f2) was used to compare the resolution profiles between time-density curves generated with commercial software on the Siemens workstation (syngo iFlow, Siemens Healthcare, Berlin, Germany) and our method. RESULTS AND COMPARISON WITH EXISTING METHOD: Sixteen patients diagnosed with acute ischemic stroke resulting from acute occlusion of the distal internal carotid artery or the first segment of the middle cerebral artery were selected for analysis. Angiography images were successfully processed with syngo iFlow and Fiji/ImageJ. The images processed with Fiji/ImageJ provided excellent anatomic and hemodynamic details. In all patients, the similarity factor (f2) values of the time-density curves derived from the same region of interest were 99.90 (range 99.85-99.95). CONCLUSIONS: The ImageJ/Fiji software provides a user-friendly and free alternative for parametric coding of digital subtraction angiography.

Optional or optimal? off-label stenting for intracranial atherosclerotic stenosis: A scoping review.

BACKGROUND: Intracranial atherosclerotic stenosis is a major cause of ischemic stroke. In addition to the Wingspan stent system, several self-expanding stents have been used off-label to treat intracranial atherosclerotic stenosis lesions. The purpose of this review is to assess the existing data on the off-label use of self-expanding stents in intracranial atherosclerotic stenosis, to highlight methodological limitations in current study designs, and thus providing strategies and precautions for clinical practice. METHODS: The PubMed, EMBASE, and the Cochrane Library databases were systematically searched for relevant articles published up to April 2022. In addition to the meta analysis of Enterprise, Neuroform EZ and closed cell stent respectively, we used a narrative synthesis to summarize and discuss the appropriate strategies and precautions for the use of each stent. RESULTS: We identified 17 studies (1091 patients with 1124 lesions) reporting 6 types of off-label self-expanding stents. The most common endpoints reported were incidence of short-term complications (range: 0-15.8%, median: 3.8%), long-term complications (range: 0-12.0%, median: 0%). Potential risks include infeasibility of stenting hard lesions or tortuous vessels, stent migration, and in-stent thrombosis. Less is known about the conditions that are appropriate for an optimal stent (e.g., open-cell, close-cell, hybrid cell). There was considerable heterogeneity across studies with regards to study populations and study designs. CONCLUSIONS: The potential risks and benefits should be carefully considered when using off-label stents for intracranial atherosclerotic stenosis, particularly given the current evidence power. As a potential option for the Wingspan stent, based on device's approval only, a tailored approach with lesion-specific devices could be beneficial in certain patients.

Spatiotemporal-aware machine learning approaches for dissolved oxygen prediction in coastal waters.

Coastal waters face increasing threats from hypoxia, which can have severe consequences for marine life and fisheries. This study aims to develop a machine learning approach for hypoxia monitoring by investigating the effectiveness of four tree-based models, considering spatiotemporal effects in model prediction, and adopting the SHapley Additive exPlanations (SHAP) approach for model interpretability, using the long-term climate and marine monitoring dataset in Tolo Harbour (Zone 1) and Mirs Bay (Zone 2), Hong Kong. The LightBoost model was found to be the most effective for predicting dissolved oxygen (DO) concentrations using spatiotemporal datasets. Considering spatiotemporal effects improved the model's bottom DO prediction performance (R2 increase 0.30 in Zone1 and 0.68 in Zone 2), although the contributions from temporal and spatial factors varied depending on the complexity of physical and chemical processes. This study focused not only on error estimates but also on model interpretation. Using SHAP, we propose that hypoxia is largely influenced by hydrodynamics, but anthropogenic activities can increase the bias of systems, exacerbating chemical reactions and impacting DO levels. Additionally, the high relative importance of silicate (Zone 1:0.11 and Zone 2: 0.19) in the model suggests that terrestrial sources, particularly submarine groundwater discharge, are important factors influencing coastal hypoxia. This is the first machine learning effort to consider spatiotemporal effects in four dimensions to predict DO concentrations, and we believe it contributes to the development of a forecasting tool for alarming hypoxia, combining real-time data and machine learning models in the near future.

Does radiological conjugate eye deviation sign play a role in acute stroke imaging? A meta-analysis.

BACKGROUND AND PURPOSE: The diagnostic value of non-contrast CT (NCCT) in acute stroke imaging remains indispensable, especially under emergency conditions with limited resources. The radiological conjugate eye deviation (RCED) has been demonstrated as a NCCT sign to predict acute ischemic stroke (AIS) or AIS secondary to large vessel occlusion (LVO) in recent studies. We performed a meta-analysis to gain a better understanding into the predictive role of RCED for AISs and LVO-AISs. METHODS: We conducted a systematic literature search using PubMed, Embase, and Cochrane. The search focused on studies published between January 2000 and August 2020 that reported the predictive value of RCED for the diagnosis of AIS or LVO-AIS. Principal measurements of the meta-analysis were the overall sensitivity, specificity, the positive likelihood ratio (PLR), and the negative likelihood ratio (NLR) of RCED in predicting AIS and LVO-AIS. RESULTS: We included 11 studies (n = 2304). For AIS, RCED had a sensitivity of 0.37 (95% CI 0.27-0.47), a specificity of 0.86 (95% CI 0.73-0.93), the area under the receiver operating characteristic curve (AUC) was 0.58 (95% CI 0.53-0.62), PLR was 2.5 (95% CI 1.5-4.4), and NLR was 0.74 (95% CI 0.65-0.84). For LVO-AIS, RCED had a sensitivity of 0.63 (95% CI 0.46-0.77), a specificity of 0.77 (95% CI 0.71-0.82), AUC was 0.63 (95% CI 0.46-0.77), PLR was 2.7 (95% CI 1.7-4.3), and NLR was 0.49 (95% CI 0.3-0.78). CONCLUSION: RCED can be used to predict LVO-AIS. It is expected that this method will be extensively used and validated in acute stroke imaging, especially under emergency conditions with limited resources.

Better late than never: initial experience of intra-arterial pulsed-urokinase-injection as a salvage therapy for refractory sudden sensorineural hearing loss.

BACKGROUND AND PURPOSE: Cochlear vascular micro-thrombosis has been hypothesized as one of the pathogenic mechanisms for sudden sensorineural hearing loss (SSNHL) refractory to regular management. This study aimed to evaluate the feasibility and safety of intra-arterial pulsed-injection urokinase (IAPU) as a salvage therapy for SSNHL after the failure of conventional therapy. METHODS: We retrospectively reviewed our patient database to identify refractory SSNHL patients between November 2017 and July 2020. Study outcomes before and after the IAPU therapy were compared between IAPU and conventional therapy groups. RESULTS: Sixty-seven moderate-profound SSNHL patients (29 in IAUP group, 38 in control group) were included in this study. Compared to the control group, patients in the IAPU group showed more significant improvement in pure tone average (PTA) (34.2 ± 23.5 vs. 10.7 ± 13.1, p < 0.001) and degree of hearing recovery (total: 20.7% vs. 5.3%, partial: 24.1% vs. 10.5%, mild: 27.6% vs. 13.2% and non: 27.6% vs. 71.1%) 2 weeks after admission. In the IAPU group, a significant improvement of PTA (86.6 ± 11.5 vs. 54.6 ± 20.1 dB, p < 0.005) was observed on the first day after IAPU treatment. CONCLUSION: In carefully selected SSNHL cases with a highly suspected vascular origin, IAPU is a safe and effective therapy when conventional treatments have failed. Despite the encouraging findings of our work, large studies are needed to better investigate the strengths and limitations of this salvage therapy.

Intraprocedural Angiographic Signs Observed During Endovascular Thrombectomy in Patients With Acute Ischemic Stroke: A Systematic Review.

OBJECTIVE: In the real-world practice of endovascular thrombectomy (EVT) for acute ischemic stroke (AIS), the analysis of intraprocedural angiographic signs (IPASs) still challenges neurointerventionists. This review provides insights into the significance of these subtle changes for predicting underlying etiology, technical feasibility, and patient prognosis, thus promoting the potential real-time application of these signs. METHODS: A systematic literature search was conducted using PubMed, Ovid Medline/Embase, and Cochrane. The search focused on studies published between January 1995 and August 2020 that reported findings related to intraprocedural angiographic manifestations in endovascular recanalization therapy for AIS. RESULTS: We identified 12 IPASs in 22 studies involving 1,683 patients. The IPASs were assigned into 3 subsets according to their clinical meanings. CONCLUSION: The systematic analysis of IPAS in clinical trials and practice will lead to a better understanding of treatment effects, responses, and mechanisms during EVT. Studies of larger cohorts using more robust statistical methods are needed.

The dynamics of dissolved inorganic nitrogen species mediated by fresh submarine groundwater discharge and their impact on phytoplankton community structure.

Submarine groundwater discharge (SGD)-driven nutrient inputs have long been speculated to sustain the high frequency of red tide occurrence in Tolo Harbour, Hong Kong, for its larger flux and higher nutrient loadings than river discharge. Based on analysis of high resolution time series biogeochemical and climatological data from 2000 to 2015, fresh SGD-derived dissolved inorganic nitrogen (DIN) is found to be a significant regulator of the annual cycle of phytoplankton community structure in the harbour. In the wet season, fresh SGD supplies nutrients with NH4+:NO3- ratio < 1 to the seawater, meanwhile creates an intensive vertical stratification environment. As a result, diatom which is a NO3- specialist, is prone to be the major group in the harbour. Fresh SGD delivers a same orders of magnitude of DIN as river and precipitation, but it is more important to phytoplankton community structure dynamics because fresh groundwater has smaller NH4+:NO3- ratio that significantly changes the ratio in the harbour. In the dry season, with the decline of fresh SGD and the ease of stratification, vertical mixing uplifts the nutrient (NH4+:NO3- ratio > 1) released from the bottom sediment leading to a NH4+ dominant environment in water column. Dinoflagellate and other groups then become dominant species of phytoplankton in the harbour. Fresh SGD has a major influence on the NH4+:NO3- ratio in the seawater compared to tide-driven SGD, even though the latter contributes a larger proportion SGD. Tide-driven SGD also produces NH4+ and NO3-, but NH4+:NO3- ratio are mainly subject to the beach environment (bare/mangrove beach), which does not change much seasonally, thus dominant DIN species do not change significantly throughout a year. In a conclusion, fresh SGD plays the most important role among all the endmembers in regulating the DIN composition in Tolo Harbour and its fluctuation mediates the phytoplankton community structure.

Muscone relieves inflammatory pain by inhibiting microglial activation-mediated inflammatory response via abrogation of the NOX4/JAK2-STAT3 pathway and NLRP3 inflammasome.

Previous studies have shown that muscone, a pharmacologically active ingredient isolated from musk, has excellent effects on anti-inflammation. However, its effect on microglia activation-induced inflammatory pain is not known yet. In the present study, a mouse BV2 microglia cell activation-mediated inflammatory model was developed with LPS induction, and a mouse inflammatory pain model was established with CFA injection. The inhibitory effect of muscone on microglia inflammatory activation was verified by measuring pro-inflammatory cytokines expression (interleukin-6, tumor necrosis factor-α, and interleukin-1ß; IL-6, TNF-α and IL-1ß). We found that muscone suppressed microglial activation-mediated inflammatory response through the NADPH oxidase 4 (NOX4)/janus kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) pathway and pyrin-domain-containing 3 (NLRP3) inflammasome. Notably, muscone mitigated CFA-induced pain hypersensitivity and inflammation, as well as microglia cell activation in vivo. Furthermore, muscone inhibited the CFA-induced NOX4, p-JAK2/p-STAT3, and NLRP3 inflammasome expression in spinal cord of mice. In conclusion, this study uncovered that muscone relieved inflammatory pain by inhibiting microglial activation-mediated inflammatory response via abrogation of the NOX4/JAK2-STAT3 pathway and NLRP3 inflammasome. This finding of muscone is promising for treating inflammatory pain.