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Background: Dementia is a serious adverse event (AE) that requires attention in clinical practice. However, information on drug-induced dementia is limited. The U.S. FDA Adverse Event Reporting System (FAERS) serves as an important resource for identifying real-world adverse drug reactions and safety signals. Objective: This study aimed to use FAERS data to identify drugs associated with increased dementia risk. Design: A secondary analysis of the FAERS database was conducted using disproportionality analysis methods. Methods: We reviewed dementia-related reports in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023, used the Medical Dictionary for Regulatory Activity to identify dementia cases and summarized the corresponding list of potential medications, counted the dementia-causing medication classes with the highest frequency of reports, and disaggregated all medications. Results: The study identified 31,881 dementia-related AEs in the FAERS database, with an increasing trend over time, particularly among females and individuals over 65. Apixaban had the most reports (1631). Disproportionality analyses revealed that rivastigmine, nicergoline, aducanumab, amlodipine/atorvastatin, and dihydroergometrine had the highest risk, based on reporting odds ratio, proportional reporting ratio, and information component. Only valproate and tramadol among the top 50 drugs included a potential dementia risk in their package inserts. Conclusion: This study identified a list of medications associated with dementia risk, many of which lack dementia warnings on their labels. Increased monitoring is necessary for high-risk individuals, and further research is required to clarify these associations and improve patient safety.

Abstract Hypertrophic pachymeningitis (HP) is a rare disorder marked by thickening of the dura mater due to diverse etiologies. MPO-ANCA-positive HP represents a variant of AAV confined to the central nervous system, distinguished by the presence of serum MPO antibodies. Distinguishing HP triggered by MPO-ANCA from other causes can be challenging. In this study, we present two cases of MPO-ANCA-positive HP initially misdiagnosed as intracranial infections. Case 1 underwent surgery for chronic suppurative otitis media, with histopathological findings revealing inflammatory changes without definitive suppuration. He was presumed to have a secondary intracranial infection resulting from the surgery. However, his condition deteriorated despite two weeks of antibiotic and antiviral treatment. Case 2 presented with headache and was initially suspected of having intracranial Brucellosis given his serum Brucella positivity. Despite treatment for brucellosis, his symptoms persisted, and he developed visual and hearing impairments. Both patients were ultimately diagnosed with MPO-ANCA-positive HP, exhibiting serum MPO antibody positivity. Their symptoms showed improvement with glucocorticoid and immunosuppressive therapy. Based on these observations, we propose that MPO-ANCA-positive HP may initially present as intracranial infection. For HP patients presenting with headache, mastoiditis, otitis media, and visual loss, it is imperative to conduct ANCA antibody-related tests to enhance diagnostic precision.

ObjectiveWhite matter hyperintensities (WMH) are the most common neuroimaging manifestation of cerebral small vessel disease, and is frequently observed in Alzheimer’s disease (AD). This study aimed to investigate the relationship between WMH and cognition and to verify the mediation of grey matter atrophy in this relationship.MethodsThe diffusion tensor imaging (DTI) technique analyses white matter fiber tract to assess white matter integrity. Voxel-based morphometry was applied to measure the grey matter volume (GMV). A linear regression model was applied to examine the associations between WMH and GMV, and mediation analyses was performed to determine the mediating role of regional GMV in the effect of WMH on cognitive function.ResultsCompared to the HC group, AD group have 8 fiber tract fractional anisotropy (FA) decreased and 16 fiber tract mean diffusivity (MD) increased. Compared to AD without WMH, AD with high WMH had 9 fiber tracts FA decreased and 13 fiber tracts MD increased. High WMH volume was negatively correlated with GMV in the frontal–parietal region. Low WMH volume was also negatively correlated with GMV except for the three regions (right angular gyrus, right superior frontal gyrus and right middle/inferior parietal gyrus), where GMV was positively correlated. Mediation analysis showed that the association between WMH and executive function or episodic memory were mediated by GMV in the frontal–parietal region.ConclusionDamage to white matter integrity was more severe in AD with WMH. Differential changes in DTI metrics may be caused by progressive myelin and axonal damage. There was a negative correlation between WMH and grey matter atrophy in frontal–parietal regions in a volume-dependent manner. This study indicates the correspondence between WMH volume and GMV in cognition, and GMV being a key modulator between WMH and cognition in AD. This result will contribute to understanding the progression of the disease process and applying targeted therapeutic intervention in the earlier stage to delay neurodegenerative changes in frontal–parietal regions to achieve better treatment outcomes and affordability.

Abstract Background Persistent somatoform pain disorder (PSPD) is often the initial diagnosis in patients seeking treatment in psychiatric departments, making it challenging to consider organic nervous system diseases. However, autoimmune encephalitis can present with atypical initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture, with antibody support, plays a crucial role in diagnosing autoimmune encephalitis. Case presentation This report describes a 40-year-old male adult patient who was initially diagnosed with persistent somatoform pain disorder in 2022. The patient reported a reduction in pain while resting on his back. There were no fever or relevant medical history. Despite 8 months of symptomatic treatment, the symptoms did not improve. Moreover, the patient developed confusion, gibberish speech, non-cooperation during questioning, and increased frequency and amplitude of upper limb convulsions. Lumbar puncture revealed elevated protein levels and protein-cell dissociation. The autoimmune encephalitis antibody NMDAR (+) was detected, leading to a diagnosis of autoimmune encephalitis (NMDAR). Conclusion Autoimmune encephalitis (NMDAR), starting with persistent somatoform pain (PSPD), often presents with atypical symptoms and can be easily misdiagnosed. Therefore, it is important to consider the possibility of organic nervous system disease in time, and to test serum or cerebrospinal fluid antibodies to rule out organic nervous system disease after symptomatic treatment of mental disorders is ineffective. This approach facilitates the early diagnosis of autoimmune encephalitis and other underlying organic neurological disorders.

Abstract The incidence of post stroke cognitive impairment (PSCI) is high in patients with mild stroke (MIS), and the risk factors and mechanism are uncertain. Increased cystatin C (CysC) levels after stroke may reflect lower glomerular filtration rate (GFR) and renal impairment. Previous studies have suggested endothelial dysfunction (ED) is closely related to renal impairment and cognitive impairment, respectively. We aimed to observe whether lower GFR estimated by CysC after MIS leaded to a high incidence of PSCI, and the role of ED in this process. 256 patients were enrolled in this prospective observational study. Renal function was assessed using GFR estimated by serum CysC. Endothelial function was evaluated by reactive hyperemia index (RHI) which calculated automatically by peripheral arterial tonometry (PAT). The cognitive function at baseline and 3 months was evaluated by MoCA score, and MoCA score ≤ 26 indicates the presence of PSCI. Spearman correlation analysis and linear regression were conducted to explore the factors affecting ED. Univariate and multivariate analysis was used to identify the independent risk factors of PSCI. The receiver operating characteristic (ROC) curve was applied to explore the optimal cutoff value of the independent risk factors levels for predicting PSCI. A total of 141 patients (55.1%) suffered from ED. Multiple linear regression analysis showed that there was a strong linear correlation between eGFRcys and RHI (p

BackgroundMigraine is a prevalent neurovascular headache disorder. The link between dietary potassium and blood pressure has been established. We sought to delineate the relationship between dietary potassium intake and the prevalence of migraines.MethodsWe conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) spanning 1999–2004, comprising 10,254 participants aged ≥20 years. Participants who reported severe headaches or migraine in the self-report questionnaire were identified as migraineurs. A 24-h dietary recall methodology was used to assess dietary potassium intake. Multivariate regression analysis and restricted cubic spline (RCS) modeling were utilized to elucidate the relationship between dietary potassium and migraines.ResultsAmong the 10,254 participants, 20.1% were identified with migraine or severe headaches. The adjusted odds ratio (OR) for migraine occurrence in the Q2 dietary potassium intake (1771–2,476 mg/d) was 0.84 (95% CI: 0.73–0.97, p = 0.021) compared to the lowest quartile (Q1, ≤ 1771 mg/d). The relationship between dietary potassium and migraine exhibited an L-shaped pattern (non-linear, p = 0.016) with an inflection at approximately 1439.3 mg/d. In the subgroup analysis, when compared to Q1, who had the lowest dietary potassium intake, the adjusted OR for Q2 in females, those in the medium-high household income group, and with a Body Mass Index (BMI) ≥ 25 kg/m2 were as follows: (OR, 0.82; 95% CI, 0.69–0.98), (OR, 0.79; 95% CI, 0.66–0.95), and (OR, 0.78; 95% CI, 0.66–0.93), respectively. No significant interaction was observed across groups after adjusting for all possible covariates.ConclusionThe relationship between dietary potassium intake and migraine prevalence among US adults appears to follow an L-shaped curve.

BackgroundObsessive-compulsive disorder (OCD) is a common reason for patients to seek symptomatic treatment in psychiatric departments, which makes it challenging to consider underlying organic nervous system diseases. However, Creutzfeldt-Jakob disease (CJD) can present with atypical symptoms, sometimes even as initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture and brain DWI are important diagnostic methods for CJD, and the detection of 1,433 protein can be performed to confirm the diagnosis.Case presentationWe present the case of a 63-year-old woman who was initially diagnosed with obsessive-compulsive disorder in 2022. Despite seven months of symptomatic treatment, her symptoms did not improve. She also developed symptoms of altered consciousness, such as upper limb tremors and mutism. Based on brain DWI and positive results from the detection of 1,433 protein, she was ultimately diagnosed with CJD.ConclusionCreutzfeldt-Jakob disease (CJD) can manifest initially as obsessive-compulsive disorder (OCD) with atypical symptoms, making it prone to misdiagnosis. Therefore, it is crucial to conduct further investigations, including lumbar puncture and imaging, to exclude organic nervous system diseases before initiating symptomatic treatment for psychiatric disorders. This approach can facilitate early diagnosis of CJD and other potential organic neurological diseases.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common kind of autoimmune encephalitis following anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. Anti-LGI1 encephalitis is characterized by cognitive impairment or rapid progressive dementia, psychiatric disorders, epileptic seizures, faciobrachial dystonic seizures (FBDS), and refractory hyponatremia. Recently, we found an atypical manifestation of anti-LGI1 encephalitis, in which paroxysmal limb weakness was the initial symptom. In this report, we describe five cases of anti-LGI1 encephalitis with paroxysmal limb weakness. Patients had similar presentations, where a sudden weakness involving a unilateral limb was observed, which lasted several seconds and occurred dozens of times each day, with the anti-LGI1 antibody being positive in both serum and cerebrospinal fluid (CSF). FBDS occurred after a mean of 12 days following paroxysmal limb weakness in three of five patients (Cases 1, 4, and 5). All patients were given high-dose steroid therapy, which had a good effect on their condition. Based on this report, we suggest that paroxysmal unilateral weakness may be a kind of epilepsy and be connected to FBDS. As an unusual neurological presentation, paroxysmal weakness can be included in the clinical manifestations of anti-LGI1 encephalitis, helping to raise awareness of the recognition of anti-LGI1 encephalitis in patients with this symptom and leading to early diagnosis and early treatment, which would contribute to improved clinical outcomes.

AimsPrevious studies have proposed the estimated pulse wave velocity (ePWV) as a simple and cost-effective measure of arterial stiffness. Since arterial stiffness plays a role in the progression of silent lacunar infarct (SLI), our present work aims to evaluate the association between ePWV and the presence of SLI.MethodsThe present work was based on a cross-section study. Our study included 1,011 neurologically healthy Korean participants. The SLI was evaluated using brain magnetic resonance images (MRI). The ePWV was derived from a published equation using age and mean blood pressure (MBP). Logistic regression analyses were performed to investigate the association between ePWV and SLI. The linear relationship and robustness were evaluated using smooth curve fitting and subgroup analyses, respectively.ResultsThe prevalence of SLI was 11.87%. After fully adjusting for covariates, per 1 m/s increase of ePWV casted 31% additional risk for SLI (P = 0.009). When dividing the ePWV into quartiles, the top quartile had 4.01 times risk compared with the bottom quartile. The increasing trend across the quartiles was statistically significant (P for trend < 0.001). Consistently, smooth curve fitting revealed that the risk of SLI elevated linearly with the increase of ePWV. Finally, subgroup analysis suggested that the association was robust in several sub-populations divided by age, sex, smoking, hypertension, diabetes mellitus (DM), coronary artery occlusive disease (CAOD), hyperlipidemia, and statin medication (all P for interaction > 0.05).ConclusionThe current study revealed an independent and positive association between ePWV and the presence of SLI in a neurologically healthy Korean population.

Abstract The existence of the blood–tumor barrier (BTB) severely hinders the transport of anti-tumor drugs to brain tumor tissues. Selectively opening BTB is of great significance to improve the chemotherapy effect of glioma. Pseudogenes have been recognized as important regulators in various biologic processes. In this study, we identified that ribosomal protein L32 pseudogene 3 (RPL32P3) was highly expressed in glioma-exposed endothelial cells (GECs). Knockdown of RPL32P3 decreased the expression of tight junction-related proteins (TJPs) and increased BTB permeability. Subsequent analysis of the underlying mechanism indicated that RPL32P3 recruited lysine methyltransferase 2 A (KMT2A) to the Y-box binding protein 2 (YBX2) promoter region and mediated H3K4me3 to promote YBX2 transcription. Highly expressed YBX2 bound and stabilized hepatocyte nuclear factor 4 gamma (HNF4G) mRNA. Highly expressed HNF4G directly bound to the promoters of TJPs ZO-1, occludin and claudin-5 to promote their transcriptional activities and regulated BTB permeability. The simultaneous knockdown of RPL32P3, YBX2, and HNF4G combined with doxorubicin (DOX) increased the apoptosis of glioma cells. In conclusion, the current study indicated that RPL32P3 knockdown increased BTB permeability through the YBX2/HNF4G pathway. These findings may provide new targets for the comprehensive treatment of glioma.

Abstract The blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.

Abstract Objectives Inflammation plays an essential role in acute ischemic stroke (AIS). Recent studies have recognized the systemic inflammation response index (SIRI) as a useful index to indicate inflammation status and predict the prognosis of multiple diseases. However, the relationship between SIRI and AIS prognosis is unclear. Our study is aimed to investigate the association between SIRI and the prognosis of AIS. Methods Our study prospectively recruited 287 consecutive patients with first‐ever stroke within 72 h after stroke. Demographic and clinical information was collected at baseline. The functional prognosis was assessed 3 months after AIS using the modified Rankin Scale (mRS). A poor outcome was defined as mRS > 2. SIRI was calculated as neutrophil × monocyte/lymphocyte count. Univariate and multivariate analyses were introduced to identify the association between SIRI and AIS prognosis. Receiver operating characteristic curve and reclassification analyses were used to evaluate the predictive value of SIRI for AIS prognosis. Results The patients with poor prognosis account for 27.5% of all participants. After fully adjusting for all covariates, each standard deviation increment of SIRI caused 58.9% additional risk for poor prognosis after AIS. When dividing SIRI into quartiles, the fourth quartile had a 6.152 times risk than the first quartile. Moreover, after adding SIRI into established clinical risk factors, AUC showed a significant improvement (0.829 vs. 0.790, p for comparison = .016). Consistently, category‐free net reclassification index (NRI, 0.761, 95% CI: 0.517–1.004, p

Abstract Background Several recent studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, the association between the evolution of dynamic neuroimaging and clinical manifestations has not been reported in patients with N2O-induced SCD. Case presentation We described the case of a 24-year-old man who developed SCD with inverted V-sign hyperintensities over the posterior aspect of the spinal cord caused by frequent, excessive N2O inhalation. One month after treatment, his weakness and paresthesia resolved and serum vitamin B12 levels exceeded the normal levels. However, the hyperintensities had extended horizontally and longitudinally on T2-weighted magnetic resonance imaging (MRI), compared to those on the initial scan. Two months after treatment, the patient experienced some residual numbness in the distal limbs, and his serum homocysteine levels were normal, but the abnormal signals seen on cervical T2-weighted MRI had decreased only slightly compared to those seen on the one-month follow-up MRI. The evolution of conventional MRI findings lagged compared to the clinical manifestation, which was suggestive of a clinical-radiological dissociation. Conclusions Clinical-radiological dissociation might have occurred in this case because T2-weighted imaging was not sensitive enough to reveal cytotoxic edema. Moreover, the serum vitamin B12 level is not a good indicator of cellular vitamin B12. Thus, clinicians should recognize this phenomenon, comprehensively assess the condition of patients with N2O-induced SCD, and avoid terminating treatment based on the resolution of clinical symptoms and serological results.

Abstract Background Recreational N2O abuse is an important etiology of neurological impairment in young patients, which may easily be ignored clinically. Few current studies have investigated the characteristics or the effects experienced by its users. We aimed to explore any correlation between the clinical severity and biomarkers and spinal magnetic resonance imaging (MRI) abnormalities, identify independent factors associated with spinal MRI abnormalities, and ascertain factors affecting depression/anxiety in patients with N2O‐related neurological disorders. Methods Patients with N2O‐related neurological disorders were enrolled retrospectively between February 2017 and July 2020. Their demographic, clinical, laboratory, neuroimaging, electrophysiological, and neuropsychological findings were analyzed. Correlation analyses were conducted using Spearman's or Pearson's correlation and linear regression analysis. Independent factors associated with spinal MRI abnormalities were identified using univariate and multivariate analyses. Results The principal clinical manifestations of N2O‐related neurological disorders (n = 63; 38 men, 25 women; mean age ± SD: 22.60 ± 4.46 years) were sensory disturbance, followed by gait disturbance and pyramidal tract damage. A significant negative correlation existed between serum vitamin B12 levels and clinical severity (r = −0.309, p = .014), which disappeared after linear regression. An interval of less than 6 months between initial N2O abuse and hospitalization was independently associated with spinal MRI abnormalities (39.47% vs. 72.00%, respectively; χ2 = 6.40, p = .01). Thirty‐eight (60.32%) and 40 (63.49%) patients experienced anxiety and depression, respectively. Moreover, the higher the clinical scores/serum homocysteine levels, the greater the severity of anxiety/depression (r = 0.442, p

Post-stroke anxiety (PSA) has caused wide public concern in recent years, and the study on risk factors analysis and prediction is still an open issue. With the deepening of the research, machine learning has been widely applied to various scenarios and make great achievements increasingly, which brings new approaches to this field. In this paper, 395 patients with acute ischemic stroke are collected and evaluated by anxiety scales (i.e., HADS-A, HAMA, and SAS), hence the patients are divided into anxiety group and non-anxiety group. Afterward, the results of demographic data and general laboratory examination between the two groups are compared to identify the risk factors with statistical differences accordingly. Then the factors with statistical differences are incorporated into a multivariate logistic regression to obtain risk factors and protective factors of PSA. Statistical analysis shows great differences in gender, age, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level between PSA group and non-anxiety group with HADS-A and HAMA evaluation. Meanwhile, as evaluated by SAS scale, gender, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level differ in the PSA group and the non-anxiety group. Multivariate logistic regression analysis of HADS-A, HAMA, and SAS scales suggest that hypertension, diabetes mellitus, drinking, high NIHSS score, and low serum HDL-C level are related to PSA. In other words, gender, age, disability, hypertension, diabetes mellitus, HDL-C, and drinking are closely related to anxiety during the acute stage of ischemic stroke. Hypertension, diabetes mellitus, drinking, and disability increased the risk of PSA, and higher serum HDL-C level decreased the risk of PSA. Several machine learning methods are employed to predict PSA according to HADS-A, HAMA, and SAS scores, respectively. The experimental results indicate that random forest outperforms the competitive methods in PSA prediction, which contributes to early intervention for clinical treatment.

Abstract Objectives Lesions limited to the bilateral middle cerebellar peduncles (MCPs) are uncommon. This retrospective study investigated diseases with a proclivity for the bilateral MCPs and explored the associations between their neuroimaging features and clinical findings for the differential diagnosis of such lesions. Methods We enrolled 26 patients who were admitted to our department between January 2016 and March 2019 with bilateral MCP abnormalities on magnetic resonance imaging (MRI). The demographic, clinical, and neuroimaging characteristics, and the biomarkers and diagnoses were evaluated. Results Although all patients exhibited symmetrical bilateral MCP hypointensities on T1‐weighted imaging and hyperintensities on T2‐weighted and fluid‐attenuated inversion recovery imaging, they were diagnosed with different conditions. Diagnoses included acute cerebral infarction (ACI) (n = 9, 34.62%), Wallerian degeneration (WD) (n = 8, 30.77%), multiple system atrophy (MSA) (n = 6, 23.08%), neuromyelitis optica (NMO) (n = 1, 3.85%), heroin‐induced leukoencephalopathy (n = 1, 3.85%), and primary central nervous system lymphoma (PCNSL) (n = 1, 3.85%). Patients with ACI exhibited bilateral MCP‐restricted diffusion hyperintensities on diffusion‐weighted imaging and corresponding stenosis or occlusion of the vertebrobasilar system. The initial MRI of patients with WD depicted pontine infarctions, while symmetrical MCP lesions were observed on follow‐up MRI. Symmetrical MCP lesions, cruciform hyperintensity, and marked atrophy in the posterior fossa were characteristic manifestations of MSA. Longitudinally extensive myelitis affecting more than three vertebral segments on cervical MRI and positive serum AQP4‐IgG may be indicative of NMO. Heroin‐induced leukoencephalopathy was characterized by extra‐symmetrical lesions in the posterior limbs of the internal capsules, while the anterior limbs were spared. PCNSL was indicated by a significant and characteristic “fist” sign on contrast‐enhanced MRI. Conclusions Bilateral MCP lesions were most frequently observed in cerebrovascular diseases, followed by neurodegenerative diseases, inflammatory diseases, toxic encephalopathies, and lymphomas. Our findings demonstrate that bilateral MCP signal abnormalities are more common in patients with ACI and WD, with fewer degenerative processes than previously believed. The high frequency of WD may be attributed to the specific awareness of this pathology. WD can also present with stage‐related restricted diffusion and should not be mistaken for a new infarction. The symmetrical bilateral MCP hypointensities on T1‐weighted imaging and hyperintensities on T2‐weighted imaging often raise concern regarding a demyelinating process. Our findings emphasize that neurologists should consider the aforementioned conditions and correlate the specific neuroimaging characteristics and medical history before arriving at the final diagnosis.

Background: Post-stroke cognitive impairment (PSCI) is a common symptom of stroke and affects the quality of life and prognosis of stroke survivors. In our study, we evaluated the efficacy of Human urinary kallidinogenase (HUK) on cognitive function in acute ischemic stroke (AIS) patients, and discussed the role of cystatin C (CysC) in improving PSCI. Methods: We enrolled a retrospective cohort with prospective follow-up. From August 2020 to May 2021, 130 patients completed the final follow-up. Among them, 61 patients received HUK combined with basic treatment, which we defined as the HUK group, and 69 patients received basic treatment, which we defined as the control group. We compared the changes of CysC, urea nitrogen and creatinine levels after one week of treatment between the two groups. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) at 3-month after AIS. Results: No significant differences in demographic data and Laboratory tests between two groups before treatment. A total of 67 patients (51.5%) were diagnosed as PSCI at 3-month follow-up, among which, 25 patients were in the HUK group and 42 patients were in the control group. Compared with the control group (60.9%), the incidence of PSCI was significantly lower in the HUK group (41.0%). In addition, the serum CysC level after a week of treatment significantly decreased from baseline in HUK group (p = 0.037), in comparison, the serum CysC level in the control group was basically unchanged (p = 0.951). There was a significant negative correlation between MoCA score and the level of CysC after treatment (p = 0.003, r = –0.373). Conclusions: HUK can reduce the risk of PSCI at 3-month in AIS patients. The decrease of serum CysC level may be one of the mechanisms by which HUK reduces the incidence of PSCI.

Background/Aims: Parkinson’s disease (PD) is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB), an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. Methods: PD was introduced in rats via injection of lipopolysaccharide (LPS) into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), CD11b and ionized calcium binding adaptor molecule (IBA)-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. Results: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. Conclusion: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.

The article discusses a study which examined the impact of luteolin on hyperglycemia-mediated apoptosis in the hippocampi of rats with streptozotocin-induced diabetic encephalopathy. Topics discussed include the inhibition of apoptosis-related factors and cytochrome c release from mitochondria, the improvement in the learning and memory abilities of rats and the role of luteolin in inhibiting apoptosis of hippocampal nerve cells in rats.

Blood–brain barrier (BBB) is specialized to limit brain drug delivery. Cross-reacting material 197 (CRM197), a non-toxic mutant of diphtheria toxin, could act as a diphtheria toxin receptor-specific carrier protein and deliver drugs across the BBB. CRM197 has previously been shown to inhibit phospatidyl-3-inositol-kinase (PI3K)/Akt signaling. Other studies have demonstrated a link between PI3K/Akt signaling and forkhead transcription factors in endothelial cells. We therefore investigated the effects and mechanisms underlying the potential of CRM197, not only as a carrier protein for targeted drug delivery to the brain, but also for inducing signaling to affect endocytosis in endothelial cells. The hCMEC/D3 cell line had been used to establish a BBB in vitro model; the transport efficiency of CRM197 was analyzed both by association and transcytosis experiments. CRM197 was shown to prefer apical-to-basal transcytosis, which involved the caveolae-mediated pathway. The uptake of CRM197 conjugates by endothelial cells reached equilibrium after 60 min of treatment. The caveolin-1 mRNA and protein expression levels were significantly increased by CRM197. The up-regulation of caveolin-1 may be mediated by CRM197 via a PI3K/Akt dependent pathway and reduction of the phospho-FOXO1A (forkhead box O) transcription factor. Our results indicate that carrier protein CRM197-mediated delivery across the BBB is involved in the induction of FOXO1A transcriptional activity and upregulation of caveolin-1 expression. [ABSTRACT FROM AUTHOR]

The article presents the correction for a article titled "Lower glomerular filtration rate after mild stroke induces cognitive impairment by causing endothelial dysfunction" published online on August 26, 2024.

Background: Dementia is a serious adverse event (AE) that requires attention in clinical practice. However, information on drug-induced dementia is limited. The U.S. FDA Adverse Event Reporting System (FAERS) serves as an important resource for identifying real-world adverse drug reactions and safety signals. Objective: This study aimed to use FAERS data to identify drugs associated with increased dementia risk. Design: A secondary analysis of the FAERS database was conducted using disproportionality analysis methods. Methods: We reviewed dementia-related reports in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023, used the Medical Dictionary for Regulatory Activity to identify dementia cases and summarized the corresponding list of potential medications, counted the dementia-causing medication classes with the highest frequency of reports, and disaggregated all medications. Results: The study identified 31,881 dementia-related AEs in the FAERS database, with an increasing trend over time, particularly among females and individuals over 65. Apixaban had the most reports (1631). Disproportionality analyses revealed that rivastigmine, nicergoline, aducanumab, amlodipine/atorvastatin, and dihydroergometrine had the highest risk, based on reporting odds ratio, proportional reporting ratio, and information component. Only valproate and tramadol among the top 50 drugs included a potential dementia risk in their package inserts. Conclusion: This study identified a list of medications associated with dementia risk, many of which lack dementia warnings on their labels. Increased monitoring is necessary for high-risk individuals, and further research is required to clarify these associations and improve patient safety. [ABSTRACT FROM AUTHOR]

Chronic cerebral ischemia (CCI) is a clinical syndrome characterised by brain dysfunction due to decreased chronic cerebral perfusion. CCI initiates several inflammatory pathways, including pyroptosis. RNA-binding proteins (RBPs) play important roles in CCI. This study aimed to explore whether the interaction between RBP-Cpeb4 and Dclk2 affected Ehf phosphorylation to regulate neuronal pyroptosis. HT22 cells and mice were used to construct oxygen glucose deprivation (OGD)/CCI models. We found that Cpeb4 and Dclk2 were upregulated in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. Cpeb4 upregulated Dclk2 expression by increasing Dclk2 mRNA stability. Knockdown of Cpeb4 or Dclk2 inhibited neuronal pyroptosis in OGD-treated HT22 cells and CCI-induced hippocampal CA1 tissues. By binding to the promoter regions of Caspase1 and Caspase3, the transcription factor Ehf reduced their promoter activities and inhibited the transcription. Dclk2 phosphorylated Ehf and changed its nucleoplasmic distribution, resulting in the exit of p-Ehf from the nucleus and decreased Ehf levels. It promoted the expression of Caspase1 and Caspase3 and stimulated neuronal pyroptosis of HT22 cells induced by OGD. Cpeb4/Dclk2/Ehf pathway plays an important role in the regulation of cerebral ischemia-induced neuronal pyroptosis. [ABSTRACT FROM AUTHOR]

Hypertrophic pachymeningitis (HP) is a rare disorder marked by thickening of the dura mater due to diverse etiologies. MPO-ANCA-positive HP represents a variant of AAV confined to the central nervous system, distinguished by the presence of serum MPO antibodies. Distinguishing HP triggered by MPO-ANCA from other causes can be challenging. In this study, we present two cases of MPO-ANCA-positive HP initially misdiagnosed as intracranial infections. Case 1 underwent surgery for chronic suppurative otitis media, with histopathological findings revealing inflammatory changes without definitive suppuration. He was presumed to have a secondary intracranial infection resulting from the surgery. However, his condition deteriorated despite two weeks of antibiotic and antiviral treatment. Case 2 presented with headache and was initially suspected of having intracranial Brucellosis given his serum Brucella positivity. Despite treatment for brucellosis, his symptoms persisted, and he developed visual and hearing impairments. Both patients were ultimately diagnosed with MPO-ANCA-positive HP, exhibiting serum MPO antibody positivity. Their symptoms showed improvement with glucocorticoid and immunosuppressive therapy. Based on these observations, we propose that MPO-ANCA-positive HP may initially present as intracranial infection. For HP patients presenting with headache, mastoiditis, otitis media, and visual loss, it is imperative to conduct ANCA antibody-related tests to enhance diagnostic precision. [ABSTRACT FROM AUTHOR]

An anatomic autopsy study showed that SCAs supplying the anterior fornix were significantly broader and longer than those that did not supply the fornix [[9]]. The fornix consists of 4 parts, that is, the fimbria hippocampi, crura of the fornix, body of the fornix, and fornicolumn. Keywords: Amnesia; Cerebral infarction; Fornix; Magnetic resonance imaging EN Amnesia Cerebral infarction Fornix Magnetic resonance imaging 139 144 5 04/24/21 20210301 NES 210301 What Causes Anterograde Amnesia? Brain MRI of the other structures. a, b Brain fluid-attenuated inversion recovery imaging shows no abnormalities in the temporal lobe, hippocampus, amygdala, thalamus, or basal forebrain. c-e Axial diffusion-weighted imaging depicts the integrity of the other regions of the fornix, medial temporal lobe memory structures, and diencepahlic memory structures. [Extracted from the article]

Background: Persistent somatoform pain disorder (PSPD) is often the initial diagnosis in patients seeking treatment in psychiatric departments, making it challenging to consider organic nervous system diseases. However, autoimmune encephalitis can present with atypical initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture, with antibody support, plays a crucial role in diagnosing autoimmune encephalitis. Case presentation: This report describes a 40-year-old male adult patient who was initially diagnosed with persistent somatoform pain disorder in 2022. The patient reported a reduction in pain while resting on his back. There were no fever or relevant medical history. Despite 8 months of symptomatic treatment, the symptoms did not improve. Moreover, the patient developed confusion, gibberish speech, non-cooperation during questioning, and increased frequency and amplitude of upper limb convulsions. Lumbar puncture revealed elevated protein levels and protein-cell dissociation. The autoimmune encephalitis antibody NMDAR (+) was detected, leading to a diagnosis of autoimmune encephalitis (NMDAR). Conclusion: Autoimmune encephalitis (NMDAR), starting with persistent somatoform pain (PSPD), often presents with atypical symptoms and can be easily misdiagnosed. Therefore, it is important to consider the possibility of organic nervous system disease in time, and to test serum or cerebrospinal fluid antibodies to rule out organic nervous system disease after symptomatic treatment of mental disorders is ineffective. This approach facilitates the early diagnosis of autoimmune encephalitis and other underlying organic neurological disorders. [ABSTRACT FROM AUTHOR]

Post-stroke anxiety (PSA) has caused wide public concern in recent years, and the study on risk factors analysis and prediction is still an open issue. With the deepening of the research, machine learning has been widely applied to various scenarios and make great achievements increasingly, which brings new approaches to this field. In this paper, 395 patients with acute ischemic stroke are collected and evaluated by anxiety scales (i.e., HADS-A, HAMA, and SAS), hence the patients are divided into anxiety group and non-anxiety group. Afterward, the results of demographic data and general laboratory examination between the two groups are compared to identify the risk factors with statistical differences accordingly. Then the factors with statistical differences are incorporated into a multivariate logistic regression to obtain risk factors and protective factors of PSA. Statistical analysis shows great differences in gender, age, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level between PSA group and non-anxiety group with HADS-A and HAMA evaluation. Meanwhile, as evaluated by SAS scale, gender, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level differ in the PSA group and the non-anxiety group. Multivariate logistic regression analysis of HADS-A, HAMA, and SAS scales suggest that hypertension, diabetes mellitus, drinking, high NIHSS score, and low serum HDL-C level are related to PSA. In other words, gender, age, disability, hypertension, diabetes mellitus, HDL-C, and drinking are closely related to anxiety during the acute stage of ischemic stroke. Hypertension, diabetes mellitus, drinking, and disability increased the risk of PSA, and higher serum HDL-C level decreased the risk of PSA. Several machine learning methods are employed to predict PSA according to HADS-A, HAMA, and SAS scores, respectively. The experimental results indicate that random forest outperforms the competitive methods in PSA prediction, which contributes to early intervention for clinical treatment. [ABSTRACT FROM AUTHOR]

Background. We aimed to examine the differences of clinical characteristics between patients with ischemic stroke with active cancer and those without cancer to develop a clinical score for predicting the presence of occult cancer in patients with ischemic stroke. Methods. This retrospective study enrolled consecutive adult patients with acute ischemic stroke who were admitted to our department between December 2017 and January 2019. The demographic, clinical, laboratory, and neuroimaging characteristics were compared between patients with ischemic stroke with active cancer and those without cancer. Multivariate analysis was performed to identify independent factors associated with active cancer. Subsequently, a predictive score was developed using the areas under the receiver operating characteristic curves based on these independent factors. Finally, Bayesian decision theory was applied to calculate the posterior probability of active cancer for finding the best scoring system. Results. Fifty-three (6.63%) of 799 patients with ischemic stroke had active cancer. The absence of a history of hyperlipidemia (odds ratio OR = 0.17 , 95% confidence interval (CI): 0.06–0.48, P < 0.01), elevated serum fibrinogen (OR = 1.72 , 95% CI: 1.33–2.22, P < 0.01) and D-dimer levels (OR = 1.43 , 95% CI: 1.24–1.64, P <0.01), and stroke of undetermined etiology (OR = 22.87 , 95% CI: 9.91–52.78, P < 0.01) were independently associated with active cancer. A clinical score based on the absence of hyperlipidemia, serum fibrinogen level of ≥4.00 g/L, and D-dimer level of ≥2.00 μg/mL predicted active cancer with an area under the curve of 0.83 (95% CI: 0.77–0.89, P < 0.01). The probability of active cancer was 59% at a supposed prevalence of 6.63%, if all three independent factors were present in a patient with ischemic stroke. Conclusions. We devised a clinical score to predict active cancer in patients with ischemic stroke based on the absence of a history of hyperlipidemia and elevated serum D-dimer and fibrinogen levels. The use of this score may allow for early intervention. Further research is needed to confirm the implementation of this score in clinical settings. [ABSTRACT FROM AUTHOR]

Previous studies have identified Atherogenic index of plasma (AIP) as a simple measure of atherosclerosis. Because atherosclerosis plays a role in the development of renal damage, our study aims to evaluate the effect of AIP on the risk of reduced eGFR and assess its usefulness to refine the risk stratification of reduced estimated glomerular filtration rate (eGFR). Our study included 15,836 participants from the National Health and Nutritional Survey (NHANES) 2009–2016. Association was investigated by logistic regression. AIP was calculated as log (triglycerides/high-density lipoprotein cholesterol). Reduced eGFR was determined as eGFR < 60 ml/min per 1.73 m*2. The prevalence of reduced eGFR was 8.01%. In the full model, each SD increase of AIP leaded to 27.4% additional risk for reduced eGFR. After dividing AIP into quartiles, the fourth quartile had a 1.649 times risk than the first quartile. Moreover, smooth curve fitting suggested that the risk of reduced eGFR elevated linearly with the increase of AIP. Subgroup analysis demonstrated that the association between AIP and reduced eGFR was robust in sex, body mass index, hypertension, and diabetes subpopulation, but the association was significantly stronger in black race and people aged less than 50 years old. Additionally, AUC displayed an advancement when introducing AIP into established risk factors (0.875 cs. 0.897, P < 0.001), category-free net reclassification index (0.249, 95% CI: 0.192–0.306, P < 0.001) and integrated discrimination index (0.007, 95% CI: 0.004–0.009, P < 0.001) also suggested the improvement from AIP. The present work suggested a linear association between AIP and reduced eGFR. Furthermore, the results showed that the association was stronger in black race and people aged less than 50 years old. Most importantly, our work implicated the usefulness of AIP to refine the risk stratification of reduced eGFR. [ABSTRACT FROM AUTHOR]

Background: Several recent studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, the association between the evolution of dynamic neuroimaging and clinical manifestations has not been reported in patients with N2O-induced SCD.Case Presentation: We described the case of a 24-year-old man who developed SCD with inverted V-sign hyperintensities over the posterior aspect of the spinal cord caused by frequent, excessive N2O inhalation. One month after treatment, his weakness and paresthesia resolved and serum vitamin B12 levels exceeded the normal levels. However, the hyperintensities had extended horizontally and longitudinally on T2-weighted magnetic resonance imaging (MRI), compared to those on the initial scan. Two months after treatment, the patient experienced some residual numbness in the distal limbs, and his serum homocysteine levels were normal, but the abnormal signals seen on cervical T2-weighted MRI had decreased only slightly compared to those seen on the one-month follow-up MRI. The evolution of conventional MRI findings lagged compared to the clinical manifestation, which was suggestive of a clinical-radiological dissociation.Conclusions: Clinical-radiological dissociation might have occurred in this case because T2-weighted imaging was not sensitive enough to reveal cytotoxic edema. Moreover, the serum vitamin B12 level is not a good indicator of cellular vitamin B12. Thus, clinicians should recognize this phenomenon, comprehensively assess the condition of patients with N2O-induced SCD, and avoid terminating treatment based on the resolution of clinical symptoms and serological results. [ABSTRACT FROM AUTHOR]

Jie Gao, Wei Xu, Kun Han, Lu Zhu, Lili Gao, Xiuli Shang Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, China Background: This was a longitudinal study which investigated the relationship between serum uric acid (SUA) and total bilirubin (Tbil) upon admission in elderly stroke patients and the occurrence of postischemic stroke depression (IPSD) at 3, 6, and 9 months of post-stroke follow-up. Subjects and methods: Data were analyzed for 525 acute ischemic stroke patients. Beck Depression Inventory (BDI) scores >17 and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were used separately to screen and diagnose IPSD at 3, 6, and 9 months post-stroke. Once IPSD was diagnosed, follow-up activities were terminated. Results: High levels of SUA (odds ratio [OR]=2.08, P

The dysfunction of the blood‐brain barrier (BBB) is one of the main pathological features of Alzheimer's disease (AD). Memantine (MEM), an N‐methyl‐d‐aspartate (NMDA) receptor antagonist, has been reported that been used widely for AD therapy. This study was performed to demonstrate the role of the MEM in regulating BBB permeability in AD microenvironment as well as its possible mechanisms. The present study showed that LINC00094 was dramatically increased in Abeta1‐42‐incubated microvascular endothelial cells (ECs) of BBB model in vitro. Besides, it was decreased in MEM‐incubated ECs. Silencing LINC00094 significantly decreased BBB permeability, meanwhile up‐regulating the expression of ZO‐1, occludin and claudin‐5. Furthermore, silencing LINC00094 enhance the effect of MEM on decreasing BBB permeability in AD microenvironment. The analysis of the mechanism demonstrated that reduction of LINC00094 inhibited Endophilin‐1 expression by up‐regulating miR‐224‐4p/miR‐497‐5p, promoted the expression of ZO‐1, occludin and claudin‐5, and ultimately alleviated BBB permeability in AD microenvironment. Taken together, the present study suggests that the MEM/LINC00094/miR‐224‐5p (miR‐497‐5p)/Endophilin‐1 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment. Silencing LINC00094 combined with MEM provides a novel target for the therapy of AD. [ABSTRACT FROM AUTHOR]

The purpose of the study was to investigate the changes of Ca2+/calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-D-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p < 0.05), and the free intracellular Ca2+ concentrations (p < 0.05). Our data reveal that salicylate administration causes tinnitus symptoms and elevates Ca2+/CaMKII/CREB signaling pathway in auditory cortex cells. Our study likely provides a new understanding of the development of tinnitus. [ABSTRACT FROM AUTHOR]

Purpose: Depressive symptoms are frequent nonmotor symptoms that occur in multiple system atrophy (MSA) patients. However, possible changes that can present in the amygdala (AMY) functional connectivity (FC) of the brain in MSA patients with depressive symptoms (DMSA patients) remain largely unknown. Materials and methods: Resting-state functional magnetic resonance imaging scans were obtained from 29 DMSA patients, 28 MSA patients without depression symptoms (NDMSA patients), and 34 healthy controls (HCs). FC was analyzed by defining the bilateral AMY as the seed region. Correlation analysis was performed between the FC and clinical scores. Results: When compared with NDMSA patients, DMSA patients showed increased bilateral AMY FC in the left middle frontal gyrus (MFG) and decreased right AMY FC in the left middle occipital gyrus. Moreover, the AMY FC values in the left middle frontal cortex were positively correlated with the Hamilton Depression Rating Scale-17 item scores. Furthermore, relative to the HCs, DMSA patients presented decreased bilateral AMY FC values in the visuospatial cortex, sensorimotor networks, and limbic areas. Conclusion: Depressive symptoms are associated with AMY–MFG FC anomalies in MSA patients. We propose that the middle frontal cortex may play an important role in the neuropathophysiology of depression in MSA patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Parkinson's disease (PD) is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB), an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. Methods: PD was introduced in rats via injection of lipopolysaccharide (LPS) into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), CD11b and ionized calcium binding adaptor molecule (IBA)-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. Results: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. Conclusion: GLB suppresses LPSinduced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro. [ABSTRACT FROM AUTHOR]