Early and enduring: Targeting the endothelium for blood-brain barrier protection.

The disruption of the blood-brain barrier marks a pivotal early pathological event in ischemic stroke that significantly contributes to subsequent permanent damage. Here we delve into the ramifications of a study conducted by Xu and colleagues, which underscores the essential role of the protein peroxiredoxin-4 in cerebrovascular endothelial cells. Peroxiredoxin-4 was shown to preserve blood-brain barrier integrity during the early stages after cerebral ischemia and reperfusion, ultimately leading to improved long-term outcomes.

Exome sequencing reveals genetic heterogeneity and clinically actionable findings in children with cerebral palsy.

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.

Updates of the role of B-cells in ischemic stroke.

Ischemic stroke is a major disease causing death and disability in the elderly and is one of the major diseases that seriously threaten human health and cause a great economic burden. In the early stage of ischemic stroke, neuronal structure is destroyed, resulting in death or damage, and the release of a variety of damage-associated pattern molecules induces an increase in neuroglial activation, peripheral immune response, and secretion of inflammatory mediators, which further exacerbates the damage to the blood-brain barrier, exacerbates cerebral edema, and microcirculatory impairment, triggering secondary brain injuries. After the acute phase of stroke, various immune cells initiate a protective effect, which is released step by step and contributes to the repair of neuronal cells through phenotypic changes. In addition, ischemic stroke induces Central Nervous System (CNS) immunosuppression, and the interaction between the two influences the outcome of stroke. Therefore, modulating the immune response of the CNS to reduce the inflammatory response and immune damage during stroke is important for the protection of brain function and long-term recovery after stroke, and modulating the immune function of the CNS is expected to be a novel therapeutic strategy. However, there are fewer studies on B-cells in brain function protection, which may play a dual role in the stroke process, and the understanding of this cell is still incomplete. We review the existing studies on the mechanisms of the role of B-cells, inflammatory response, and immune response in the development of ischemic stroke and provide a reference for the development of adjuvant therapeutic drugs for ischemic stroke targeting inflammatory injury.

Dewatering and strength characteristics of dredged slurry under curing-flocculation-vacuum filtration.

Addressing the substantial yearly production of waste dredged slurry with high water content, it is imperative to adopt effective technical treatments for sustainable development. This paper establishes that the curing-flocculation-vacuum filtration (C-F-VF) method efficiently converts high-water content dredged slurry into back-fill soil, achieving rapid dewatering. The study delves into the mechanism facilitating swift dewatering and the heightened mechanical properties of the dewatered soil. The synergy of curing, flocculation, and vacuum filtration expedites the dewatering process. The pre-addition of a curing agent reduces the zeta potential of the slurry, enhancing its efficiency in subsequent flocculation and vacuum filtration. Although the curing agent experiences some loss during vacuum filtration, over 91.22% remains in the dewatered soil, fortifying its strength. Soil strength correlates with the water content post-vacuum filtration and the amount of cement added pre-filtration, with a proposed relevant strength prediction formula.

Optimizing sludge dewatering efficiency with ultrasonic Treatment: Insights into Parameters, Effects, and microstructural changes.

Sludge dewatering plays a critical role in the efficient and cost-effective management of wastewater treatment plants. Ultrasonic treatment has emerged as a promising technique for improving dewatering processes. This study aims to evaluate the impact of ultrasonic treatment on sludge dewatering characteristics. A series of experiments were conducted to evaluate the dewatering characteristics of sludge under ultrasonic treatment. Experimental data was collected, and the effects of ultrasonic parameters on dewatering efficiency were analyzed. Ultrasound has the capacity to disintegrate sludge flocs, liberate tightly bound water, and enhance sludge dewatering capabilities. The application of ultrasound leads to the breakdown of sludge flocs, which facilitates a substantial amount of organic acids or carbonates. This, in turn, modifies the pH value of the sludge. Additionally, ultrasound induces instantaneous high temperature and pressure within the liquid phase, consequently elevating the temperature of the sludge slurry. Optimum ultrasound energy density and duration of ultrasound treatment exist. For the sludge samples analyzed in this investigation, it was determined that the optimal ultrasonic energy density is 9.8 W, while the optimal duration of ultrasound treatment is 30 s. Excessively escalating the sound energy density or prolonging the duration of ultrasound may yield unfavorable outcomes in terms of sludge dewatering effectiveness. To enhance sludge dewatering, it is crucial to select appropriate ultrasonic energy density and duration of ultrasonic treatment. This study demonstrates the positive impact of ultrasonic treatment on the dewatering characteristics of sludge. The findings provide valuable insights into the potential of ultrasonic technology for enhancing sludge dewatering.

Role of microRNA-34a in blood-brain barrier permeability and mitochondrial function in ischemic stroke.

Over the past decade, there has been an uptick in the number of studies conducting research on the role of microRNA (miRNA) molecules in stroke. Among these molecules, miR-34a has emerged as a significant player, as its levels have been observed to exhibit a substantial rise following ischemic events. Elevated levels of miR-34a have been found to have multiple effects, including the modulation of inflammatory molecules involved in the post-stroke recovery process, as well as negative effects on the blood-brain barrier (BBB) permeability. Interestingly, the increase of miR-34a appears to increase BBB permeability post stroke, through the negative effect on mitochondrial function. The strength of mitochondrial function is crucial for limiting para-cellular permeability and maintaining the structural integrity of the BBB. Furthermore, the activation of ischemic repair mechanisms and the reduction of ischemic event damage depend on healthy mitochondrial activity. This review aims to emphasize the involvement of miR-34a in ischemic stroke, specifically its interaction with mitochondrial genes in cerebrovascular endothelial cells, the effect on mitochondrial function, and lastly its regulatory role in BBB permeability. A comprehensive understanding of the role of miR-34a in maintaining BBB integrity and its contribution to the pathogenesis of stroke holds significant value in establishing a foundation for the development of future therapeutics and diagnostic markers.

Grape Seed Proanthocyanidins Improve the Quality of Fresh and Cryopreserved Semen in Bulls.

Oxidative stress leads to a decrease in semen quality during semen cryopreservation and fresh semen production. Grape seed proanthocyanidins (GSPs) are endowed with well-recognized antioxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Therefore, the objective of this experiment was to explore the effects of GSPs on the quality of fresh and cryopreserved semen to provide a basis for GSPs as a new dietary additive and semen diluent additive for males' reproduction. Fresh semen from three healthy bulls aged 3 to 5 years old were gathered and mixed with semen diluents dissolved with 0 µg/mL, 30 µg/mL, 40 µg/mL, 50 µg/mL, and 60 µg/mL GSPs respectively. The motility, physiological structures (acrosome integrity, membrane integrity, mitochondrial activity), and antioxidant capacity of frozen-thawed sperm were measured after storage in liquid nitrogen for 7 days (d). Bulls were fed with 20 mg/kg body weight (BW) GSPs in their diet for 60 days; the weight of the bull is about 600 kg. Then, the reproductive performance and antioxidant indexes of bulls were measured before and after feeding. The results demonstrated that GSPs supplementation significantly increased sperm motility, physiological structures, GSH-Px, and CAT enzyme activities and significantly decreased MDA content in sperm during semen cryopreservation. The optimal concentration of GSPs was 40 µg/mL (p < 0.05). After 20 mg/kg (body weight) GSP supplementation, sperm motility was significantly heightened (p < 0.05), the sperm deformity rate was significantly reduced (p < 0.05), and antioxidant enzyme activities (such as SOD, CAT, and GSH-Px) were significantly enhanced (p < 0.05), and the production of MDA was significantly suppressed (p < 0.05) in serum compared with that before feeding. In conclusion, these results reveal that a certain concentration of GSPs has a good protective effect on sperm damage caused by semen cryopreservation and the reproductive performance reduction caused by stress in bulls, which may be attributed to the antioxidant function of GSPs. In summary, GSPs are a useful cryoprotective adjuvant and dietary additive for bull sperm quality.

New insight into the additives in preparation and reduction of shield slurry.

In the preparation of the slurry in the slurry shield (SSS) and subsequent reduction of the waste slurry produced by the slurry shield (WSSS), the additives in SSS improve the quality of filtration cake on the excavation surface, but they may also remain in WSSS, which have a negative impact on the reduction efficiency of WSSS. Therefore, it is valuable to establish the relationship between SSS and WSSS with additives as a link. Given this, this paper prepared WSSS with different dosages of additives and studied the influence of residual additives on the reduction. The residual additives made the reduction efficiency of WSSS worse, and the specific resistance to filtration increased by one to two orders of magnitude. The residual additives change the content of bound water or reduce the available sites of the soil particles that can be adsorbed by flocculants, leading to worse reduction results. To reduce the difficulty of reduction, combining polymer and bentonite as additives are recommended to prepare SSS. Polyaluminium chloride (PAC) acts by reducing bound water content through the interaction with residual bentonite, simultaneously augmenting PAM flocculation, which is recommended for reducing WSSS. This paper provides a reference for selecting materials used to prepare SSS and the subsequent reduction of WSSS.

Endoscopic far-lateral supracerebellar infratentorial approach for resection of dumbbell-shaped trigeminal schwannoma: surgical techniques and preliminary results.

BACKGROUND: Trigeminal schwannomas (TSs) are mostly benign tumors. However, dumbbell-shaped TSs are most challenging for surgeons and pose a high surgical risk. OBJECTIVE: We describe the technique of the purely endoscopic far-lateral supracerebellar infratentorial approach (EFL-SCITA) for removing dumbbell-shaped TSs and further discuss the feasibility of this approach and our experience. METHODS: EFL-SCITA was performed for resection of 5 TSs between January 2020 and March 2023. The entire procedure was performed endoscopically with the goal of total tumor resection. During the operation, the tumor was exposed in close proximity and multiple angles under the endoscope, and the peri-tumor nerves were carefully identified and protected, especially the normal trigeminal fiber bundles around the tumor. RESULTS: All the tumors of 5 patients involved the middle and posterior cranial fossa, of which total removal was achieved in 2 patients and near-total removal in 3 patients. The most common preoperative symptoms were relieved after surgery. Two patients had postoperative mild facial paralysis (House-Brackmann grade II), and 1 patient had abducens palsy; both recovered during the follow-up period. Two patients experienced new postoperative facial hypesthesia, and 1 experienced mastication weakness, which did not recover. There was no tumor recurrence or residual tumor growth during the follow-up period in any of the patients. CONCLUSION: EFL-SCITA is a new and effective alternative for the surgical treatment of TSs. For dumbbell-shaped TSs, this approach provides sufficient surgical field exposure and freedom of operation.

A novel specific aptamer targets cerebrovascular endothelial cells after ischemic stroke.

Cell specific-targeted therapy (CSTT) for acute ischemic stroke remains underdeveloped. Cerebrovascular endothelial cells (CECs) are key components of the blood-brain barrier and are the first brain cells affected by ischemic stroke. After stroke, CEC injury causes insufficient energy supply to neurons and leads to cytotoxic and vasogenic brain edema. Aptamers are short single-stranded RNA or DNA molecules that can bind to specific ligands for cell specific delivery. The expression of vascular cell adhesion molecule-1 (VCAM-1) is increased on CECs after stroke. Herein, we report that an RNA-based VCAM-1-aptamer can specifically target CECs in stroke brains following transient middle cerebral artery occlusion in mice. Our data demonstrate the potential of an RNA-based aptamer as an effective delivery platform to target CECs after stroke. We believe this method will allow for the development of CSTT for treatment of patients with stroke.

Lnc-TRTMFS promotes milk fat synthesis via the miR-132x/RAI14/mTOR pathway in BMECs.

As an important index to evaluate the quality of milk, milk fat content directly determines the nutrition and flavor of milk. Recently, growing evidence has suggested that long noncoding RNAs (lncRNAs) play important roles in bovine lactation, but little is known about the roles of lncRNAs in milk fat synthesis, particularly the underlying molecular processes. Therefore, the purpose of this study was to explore the regulatory mechanism of lncRNAs in milk fat synthesis. Based on our previous lncRNA-seq data and bioinformatics analysis, we found that Lnc-TRTMFS (transcripts related to milk fat synthesis) was upregulated in the lactation period compared to the dry period. In this study, we found that knockdown of Lnc-TRTMFS significantly inhibited milk fat synthesis, resulting in a smaller amount of lipid droplets and lower cellular triacylglycerol levels, and significantly decreased the expression of genes related to adipogenesis. In contrast, overexpression of Lnc-TRTMFS significantly promoted milk fat synthesis in bovine mammary epithelial cells (BMECs). In addition, Bibiserv2 analysis showed that Lnc-TRTMFS could act as a molecular sponge for miR-132x, and retinoic acid induced protein 14 (RAI14) was a potential target of miR-132x, which was further confirmed by dual-luciferase reporter assays, quantitative reverse transcription PCR, and western blots. We also found that miR-132x significantly inhibited milk fat synthesis. Finally, rescue experiments showed that Lnc-TRTMFS could weaken the inhibitory effect of miR-132x on milk fat synthesis and rescue the expression of RAI14. Taken together, these results revealed that Lnc-TRTMFS regulated milk fat synthesis in BMECs via the miR-132x/RAI14/mTOR pathway.

Milk fat is an important index to evaluate the quality of milk. The content of milk fat directly determines the quality and flavor of milk. Studies have shown that milk components can change with the expression of specific genes and noncoding RNA that regulate it in different lactation periods. In this study, after the interference and overexpression of Lnc-TRTMFS on milk fat metabolism in bovine mammany epithelial cells, we found that Lnc-TRTMFS could positively regulate milk fat synthesis in bovine mammary epithelial cells. The ceRNA network of Lnc-TRTMFS-miR-132x-RAI14 was constructed by software prediction and double fluorescein report test, and the salvage effect of Lnc-TRTMFS on milk fat synthesis was confirmed by salvage test. Most importantly, we found that Lnc-TRTMFS and miR-132x can regulate milk fat by regulating the mTOR pathway by regulating RAI14.

Leaf Extract of Perilla frutescens (L.) Britt Promotes Adipocyte Browning via the p38 MAPK Pathway and PI3K-AKT Pathway.

The leaf of Perilla frutescens (L.) Britt (PF) has been reported to negatively affect adipocyte formation, inhibit body-fat formation, and lower body weight. However, its effect on adipocyte browning remains unknown. Thus, the mechanism of PF in promoting adipocyte browning was investigated. The ingredients of PF were acquired from the online database and filtered with oral bioavailability and drug-likeness criteria. The browning-related target genes were obtained from the Gene Card database. A Venn diagram was employed to obtain the overlapped genes that may play a part in PF promoting adipocyte browning, and an enrichment was analysis conducted based on these overlapped genes. A total of 17 active ingredients of PF were filtered, which may regulate intracellular receptor-signaling pathways, the activation of protein kinase activity, and other pathways through 56 targets. In vitro validation showed that PF promotes mitochondrial biogenesis and upregulates brite adipocyte-related gene expression. The browning effect of PF can be mediated by the p38 MAPK pathway as well as PI3K-AKT pathway. The study revealed that PF could promote adipocyte browning through multitargets and multipathways. An in vitro study validated that the browning effect of PF can be mediated by both the P38 MAPK pathway and the PI3K-AKT pathway.

Rab32 promotes glioblastoma migration and invasion via regulation of ERK/Drp1-mediated mitochondrial fission.

The highly widespread and infiltrative nature of glioblastoma multiforme (GBM) makes complete surgical resection hard, causing high recurrence rate and poor patients' prognosis. However, the mechanism underlying GBM migration and invasion is still unclear. In this study, we investigated the role of a Ras-related protein Rab32 on GBM and uncovered its underlying molecular and subcellular mechanisms that contributed to GBM aggressiveness. The correlation of Rab32 expression with patient prognosis and tumor grade was investigated by public dataset analysis and clinical specimen validation. The effect of Rab32 on migration and invasion of GBM had been evaluated using wound healing assay, cell invasion assay, as well as protein analysis upon Rab32 manipulations. Mitochondrial dynamics of cells upon Rab32 alterations were detected by immunofluorescence staining and western blotting. Both the subcutaneous and intracranial xenograft tumor model were utilized to evaluate the effect of Rab32 on GBM in vivo. The expression level of Rab32 is significantly elevated in the GBM, especially in the most malignant mesenchymal subtype, and is positively correlated with tumor pathological grade and poor prognosis. Knockdown of Rab32 attenuated the capability of GBM's migration and invasion. It also suppressed the expression levels of invasion-related proteins (MMP2 and MMP9) as well as mesenchymal transition markers (N-cadherin, vimentin). Interestingly, Rab32 transported Drp1 to mitochondrial from the cytoplasm and modulated mitochondrial fission in an ERK1/2 signaling-dependent manner. Furthermore, silencing of Rab32 in vivo suppressed tumor malignancy via ERK/Drp1 axis. Rab32 regulates ERK1/2/Drp1-dependent mitochondrial fission and causes mesenchymal transition, promoting migration and invasion of GBM. It serves as a novel therapeutic target for GBM, especially for the most malignant mesenchymal subtype. Schematic of Rab32 promotes GBM aggressiveness via regulation of ERK/Drp1-mediated mitochondrial fission. Rab32 transports Drp1 from the cytoplasm to the mitochondria and recruits ERK1/2 to activate the ser616 site of Drp1, which in turn mediates mitochondrial fission and promotes mesenchymal transition, migration and invasion of GBM.

Multi-omics analysis of N6-methyladenosine reader IGF2BP3 as a promising biomarker in pan-cancer.

Background: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has been reported to exhibit an oncogenic effect as an RNA-binding protein (RBP) by promoting tumor cell proliferation, migration and invasion in several tumor types. However, a pan-cancer analysis of IGF2BP3 is not currently available, and the exact roles of IGF2BP3 in prognosis and immunology in cancer patients remain enigmatic. The main aim of this study was to provide visualization of the systemic prognostic landscape of IGF2BP3 in pan-cancer and to uncover the potential relationship between IGF2BP3 expression in the tumor microenvironment and immune infiltration profile. Methods: Raw data on IGF2BP3 expression were obtained from GTEx, CCLE, TCGA, and HPA data portals. We have investigated the expression patterns, diagnostic and prognostic significance, mutation landscapes, functional analysis, and functional states of IGF2BP3 utilizing multiple databases, including HPA, TISIDB, cBioPortal, GeneMANIA, GESA, and CancerSEA. Moreover, the relationship of IGF2BP3 expression with immune infiltrates, TMB, MSI and immune-related genes was evaluated in pan-cancer. IGF2BP3 with drug sensitivity analysis was performed from the CellMiner database. Furthermore, the expression of IGF2BP3 in different grades of glioma was detected by immunohistochemical staining and western blot. Results: We found that IGF2BP3 was ubiquitously highly expressed in pan-cancer and significantly correlated with diagnosis, prognosis, TMB, MSI, and drug sensitivity in various types of cancer. Besides, IGF2BP3 was involved in many cancer pathways and varied in different immune and molecular subtypes of cancers. Additionally, IGF2BP3 is critically associated with genetic markers of immunomodulators in various cancers. Finally, we validated that IGF2BP3 protein expression was significantly higher in glioma than in normal tissue, especially in GBM. Conclusions: IGF2BP3 may be a potential molecular biomarker for diagnosis and prognosis in pan-cancer, especially for glioma. It could become a novel therapeutic target for various cancers.

Distribution and changes in microplastics in Taihu Lake and cyanobacterial blooms formed by the aggregation of Microcystis colonies.

As a new type of pollutant, microplastics have attracted much attention. As the third largest freshwater lake in China, Taihu Lake is characterized by severe eutrophication caused by external pollution and frequent occurrence of cyanobacterial blooms. Although there have been previous investigations into the spatial distribution of microplastics in Taihu Lake, research on the relationships among microplastics, pollutants, and cyanobacterial blooms, as well as the spatiotemporal distribution and changing characteristics of microplastics, is deficient. This study investigated the characteristics of microplastics, pollutants, and cyanobacterial blooms in the surface water and sediments of Taihu Lake. The abundances of microplastics were 0-3.7 items/L in the surface water and 44.42-417.56 items/kg (dry weight) in the sediments. Microplastics are most abundant in the western, southern, and northern lake areas. The northern and western lake areas are severely polluted, and cyanobacterial blooms are prone to occur in these areas. This study found that microplastics exist in the surface water of the southeastern lake area, which is a source of drinking water, and the microplastics may thus have adverse effects on drinking water quality. As the main organisms in the cyanobacterial blooms, Microcystis and microplastics have similar spatial distributions in Taihu Lake and are both affected by wind. Based on a combination of the investigations of this paper with the existing research on the microplastics in Taihu Lake, the spatiotemporal distribution of microplastics was obtained: the abundance of microplastics in surface water has continuously decreased, there are no obvious spatial distribution differences, and the spatial distribution of microplastics in the sediments is the same as that in the surface water.

Endoscopic transcortical expanded transforaminal transvenous transchoroidal approach to third ventricle lesion resection using an endoport.

OBJECTIVE: To investigate the clinical experience and application value of endoscopic resection of lesions in and around the third ventricle using a transcortical expanded transforaminal transvenous transchoroidal approach with an endoport. METHODS: Clinical data and follow-up results of seven patients who underwent the removal of lesions in the third ventricle and its adjacent area with an endoport-guided endoscopic system from January 2018 to December 2020 in the Department of Neurosurgery, Zhongshan Hospital Affiliated to Fudan University, were analyzed retrospectively. Two other patients from the Affiliated Pediatric Hospital of Fudan University and the Affiliated Hospital of Guizhou Medical University, respectively, were included in the analysis. RESULTS: A total of nine cases of third ventricle tumors were included in the study, including six women and three men, with an average age of 37.8 years (4-84 years old) and a follow-up time of 6-44 months. These nine tumor cases included two pilocytic astrocytomas, one diffuse midline glioma (H3 K27-altered), two craniopharyngiomas, two choroid plexus (CP) papillomas, one germinoma, and one pineal parenchymal tumor of intermediate differentiation. Total resection was completed in eight cases, with one near-total resection. There were no complications related to the surgical approach, such as epilepsy, aphasia, or hemiplegia. CONCLUSIONS: The endoscope transcortical expanded transforaminal transvenous transchoroidal approach using an endoport can safely and effectively remove third ventricle lesions. This approach can reach a wide area, from the anterior to the posterior third ventricle.

Endoscopic resection of thalamic lesions via supracerebellar infratentorial approach: a case series and technical note.

The deep location of the thalamus and the complex neural circuits in the surrounding area make surgery extremely challenging. Feasibility and advisability of using a supracerebellar infratentorial approach (SCITA) for endoscopic resection of thalamic lesions remains to be further evaluated. Fifteen patients who underwent endoscopic resection of thalamic via SCITA from 2014 to 2021 were retrospectively collected. We analyzed preoperative tumor-related variables and surgical procedures in detail, as well as postoperative outcomes. Lesions mainly located in the posterior and/or medial part of the thalamus, and some of them expanded downward, or backward. The mean size of them was 30 × 24 mm. Five of the nine patients with preoperative hydrocephalus underwent cerebrospinal fluid shunts to relieve increased intracranial pressure. Among the 15 patients, 4 were glioblastoma, 3 were pilocytic astrocytoma, and the rest included 1 case of anaplastic astrocytoma, melanoma, polymorphous low-grade neuroepithelial tumor of the young, rosette-forming glioneuronal tumor, inflammatory lesion, diffuse midline glioma, and cavernous hemangioma. The majority of patients (10/15) achieved gross total resection, which has become more pronounced since paramedian SCITA was used in place of the midline approach in 2020 (6/8). Three patients had unresolved or new onset of clinical symptoms after surgery, resulting in a decreased KPS score at discharge. Neuro-endoscopic techniques can ameliorate many of the shortcomings of the SCITA. With the accumulation of experience and technological progress, more deficiencies of this approach may be improved, enabling safe and effective resection of posterior and/or medial part thalamic lesions.

Corrigendum: Neurological adverse events associated with esketamine: A disproportionality analysis for signal detection leveraging the FDA adverse event reporting system.

[This corrects the article DOI: 10.3389/fphar.2022.849758.].

Neuronavigation-Guided Transcortical-Transventricular Endoport-Assisted Endoscopic Resection for Thalamic Lesions: Preliminary Experience.

BACKGROUND: Surgery for thalamic lesions is generally challenging because they are deep-seated lesions surrounded by vital neurovascular structures. Whether neuronavigation-guided transcortical-transventricular endoport-assisted endoscopic resection for thalamic lesions is feasible remains to be further evaluated. METHODS: A retrospective review of 8 who patients received neuronavigation-guided transcortical-transventricular endoport-assisted endoscopic resection for thalamic lesions was performed. Preoperative and tumor-related variables and postoperative outcomes were analyzed. RESULTS: All lesions were located in the medial part of the thalamus, and most of them expanded forward, downward, or backward. Median size of lesions was 31 mm (range, 16-52 mm). Final pathology results confirmed that 1 case was a cavernous malformation, 3 were pilocytic astrocytomas, and 4 were glioblastomas. None of the patients had postoperative seizures. Gross total resection and long-term postoperative survival were achieved in all patients with benign lesions, while near-total resection (>90%) was achieved in 3 of 4 patients (75%) with glioblastoma, and subtotal resection (<90%) was achieved in 1 patient (25%). Among patients with glioblastoma, 1 patient remained free of recurrence at 16 months of follow-up; the other 3 patients had worse Karnofsky performance scale scores after surgery and died within 6 months. CONCLUSIONS: Combining the advantages of neuronavigation, endoscopy, and endoport techniques via the middle frontal gyrus approach can safely and effectively remove benign lesions in the medial part of the thalamus. This procedure can also be performed in well-selected cases of glioblastoma and likely confers a survival advantage for this rapidly and universally fatal disease.

Neurological Adverse Events Associated With Esketamine: A Disproportionality Analysis for Signal Detection Leveraging the FDA Adverse Event Reporting System.

Esketamine was approved for the treatment of treatment-resistant depression in 2019. After the approval of esketamine, numerous concerns have been raised regarding its long-term safety and tolerability. A previous systematic pharmacovigilance study on esketamine-related adverse events (AEs) was published in 2020; however, it has not been updated 2 years later. The primary aim of this study was to detect and characterize neurological safety signals of esketamine to partially update the knowledge in this field using the FDA pharmacovigilance database. Reporting odds ratio (ROR) was calculated for esketamine-related neurological AEs from 2019 to 2021 with a signal considered when the lower limit of the 95% confidence interval (CI) of ROR (ROR025) exceeded one. Severe and non-severe cases were compared using an independent samples t-test or chi-squared (χ2) test, and a rating scale was used to prioritize the signals. The database contained 720 cases of esketamine-associated neurological AEs, with 21 signals detected, ranging from a ROR025 of 1.05 (disturbance in attention) to 204.00 (sedation). 16 latest neurological AEs emerged in the second year of marketing approval of esketamine, with eight signals detected. The associations between esketamine and nervous system disorders persisted when stratifying by sex, age, and reporter type, whereas the spectrum of neurological AEs differed in stratification regimens. Esketamine dosage, antidepressant polypharmacy, or co-prescription with benzodiazepines affected AEs severity (t = 2.41, p = 0.017; χ2 = 6.75, p = 0.009; and χ2 = 4.10, p = 0.043; respectively), while age and sex did not (p = 0.053 and p = 0.397, respectively). Three signals were categorized as moderate clinical priority [i.e., sedation, dizziness, and dysgeusia (priority points 7, 5, and 5, respectively)], showing the same early failure type profiles. Notably, seven detected disproportionality signals were not previously detected in clinical trials. Although the majority of results were in line with those obtained in the previous study, there were discrepancies in the spectrum of neurological AEs and the effects of several risk factors on AEs severity among the two studies that should be recognized and managed early in clinical treatments.