Antiproliferative and apoptotic effects of telmisartan in human glioma cells.

Glioblastoma is the most common primary central nervous system tumor in adults. Angiotensin II receptor blockers (ARBs) are broadly applied to treat hypertension. Moreover, research has revealed that ARBs have the capacity to suppress the growth of several cancer types. In this study, we assessed the effects of three ARBs with the ability to cross the blood brain barrier (telmisartan, valsartan and fimasartan) on cell proliferation in three glioblastoma multiforme (GBM) cell lines. Telmisartan markedly suppressed the proliferation, migration, and invasion of these three GBM cell lines. Microarray data analysis revealed that telmisartan regulates DNA replication, mismatch repair, and the cell cycle pathway in GBM cells. Furthermore, telmisartan induced G0/G1 phase arrest and apoptosis. The bioinformatic analysis and western blotting results provide evidence that SOX9 is a downstream target of telmisartan. Telmisartan also suppressed tumor growth in vivo in an orthotopic transplant mouse model. Therefore, telmisartan is a potential treatment for human GBM.

Pathophysiology of Chronic Migraine: Insights from Recent Neuroimaging Research.

PURPOSE OF REVIEW: Chronic migraine (CM) is a highly disabling primary headache disorder with a substantial impact on patients' quality of life. Episodic migraine (EM) and CM are dynamic states; CM usually evolves from EM alongside increased headache frequency, comorbidities, and medication overuse, supporting the notion that migraine is a spectrum disorder. This narrative review aims to summarize neuroimaging studies to better understand the pathophysiology of CM. RECENT FINDINGS: Positron emission tomography studies have revealed abnormal energy metabolism and metabolic changes in the dorsal rostral pons in individuals with CM, suggesting that this structure has a key role in the pathophysiology of migraine generation and chronification. Magnetic resonance spectroscopy studies have suggested that thalamocortical pathway dysfunction may contribute to migraine chronification, while functional magnetic resonance imaging studies have highlighted that hypothalamic activity may be involved. Recent evidence highlights functional and structural alterations in cortical and subcortical pain-related brain regions in patients with CM. Whether these functional and structural abnormalities of the brain cause migraine chronification or are a consequence of repeated attacks is still debated. In the future, imaging patterns that predict the transformation from EM to CM should be identified.

Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux.

Diosmin, a natural flavone glycoside acquired through dehydrogenation of the analogous flavanone glycoside hesperidin, is plentiful in many citrus fruits. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor; the average survival time of GBM patients is less than 18 months after standard treatment. The present study demonstrated that diosmin, which is able to cross the blood-brain barrier, inhibited GBM cell growth in vitro and in vivo. Diosmin also impeded migration and invasion by GBM8401and LN229 GBM cells by suppressing epithelial-mesenchymal transition, as indicated by increased expression of E-cadherin and decreased expression of Snail and Twist. Diosmin also suppressed autophagic flux, as indicated by increased expression of LC3-II and p62, and induced cell cycle arrest at G1 phase. Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.

GRPEL2 Knockdown Exerts Redox Regulation in Glioblastoma.

Malignant brain tumors are responsible for catastrophic morbidity and mortality globally. Among them, glioblastoma multiforme (GBM) bears the worst prognosis. The GrpE-like 2 homolog (GRPEL2) plays a crucial role in regulating mitochondrial protein import and redox homeostasis. However, the role of GRPEL2 in human glioblastoma has yet to be clarified. In this study, we investigated the function of GRPEL2 in glioma. Based on bioinformatics analyses from the Cancer Gene Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we inferred that GRPEL2 expression positively correlates with WHO tumor grade (p < 0.001), IDH mutation status (p < 0.001), oligodendroglial differentiation (p < 0.001), and overall survival (p < 0.001) in glioma datasets. Functional validation in LN229 and GBM8401 GBM cells showed that GRPEL2 knockdown efficiently inhibited cellular proliferation. Moreover, GRPEL2 suppression induced cell cycle arrest at the sub-G1 phase. Furthermore, GRPEL2 silencing decreased intracellular reactive oxygen species (ROS) without impending mitochondria membrane potential. The cellular oxidative respiration measured with a Seahorse XFp analyzer exhibited a reduction of the oxygen consumption rate (OCR) in GBM cells by siGRPEL2, which subsequently enhanced autophagy and senescence in glioblastoma cells. Taken together, GRPEL2 is a novel redox regulator of mitochondria bioenergetics and a potential target for treating GBM in the future.

CKAP2L Knockdown Exerts Antitumor Effects by Increasing miR-4496 in Glioblastoma Cell Lines.

Despite advances in the diagnosis and treatment of the central nervous system malignancy glioma, overall survival remains poor. Cytoskeleton-associated protein 2-like (CKAP2L), which plays key roles in neural progenitor cell division, has also been linked to poor prognosis in lung cancer. In the present study, we investigated the role of CKAP2L in glioma. From bioinformatics analyses of datasets from The Cancer Gene Atlas and the Chinese Glioma Genome Atlas, we found that CKAP2L expression correlates with tumor grade and overall survival. Gene set enrichment analysis (GSEA) showed that MITOTIC_SPINDLE, G2M_CHECKPOINT, and E2F_TARGETS are crucially enriched phenotypes associated with high CKAP2L expression. Using U87MG, U118MG, and LNZ308 human glioma cells, we confirmed that CKAP2L knockdown with siCKAP2L inhibits glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition. Interestingly, CKAP2L knockdown also induced cell cycle arrest at G2/M phase, which is consistent with the GSEA finding. Finally, we observed that CKAP2L knockdown led to significant increases in miR-4496. Treating cells with exogenous miR-4496 mimicked the effect of CKAP2L knockdown, and the effects of CKAP2L knockdown could be suppressed by miR-4496 inhibition. These findings suggest that CKAP2L is a vital regulator of miR-4496 activity and that CKAP2L is a potentially useful prognostic marker in glioma.

Pneumatosis cystoides intestinalis in a patient with aseptic meningitis: a case report.

BACKGROUND: Although pneumatosis cystoides intestinalis (PCI) is observed in patients who are on corticosteroid treatment, most patients have underlying diseases requiring long-term corticosteroid treatment. Herein, we present a rare case of a patient with aseptic meningitis who had PCI of the ascending colon while receiving betamethasone treatment. CASE PRESENTATION: A 46-year-old man was sent to our institution due to disturbance in consciousness and general weakness. Brain computed tomography (CT) scan showed multiple hyperdense lesions over the bilateral hemisphere at the white-gray matter junction. Empiric antibiotic treatment with vancomycin and ceftriaxone was prescribed. Due to acute generalized exanthematous pustulosis (AGEP), we ordered betamethasone and diphenhydramine. Two days later, the patient had bloating and abdominal tenderness. Moreover, contrast-enhanced abdominal CT scan revealed PCI of the ascending colon. Since ischemic bowel disease was suspected, laparoscopy and colonoscopy were carried out. However, no abnormal mucosa or mass lesion was noted. Then, tachycardia, hypotension, and change in consciousness along with loss of brainstem reflex and increased intracranial pressure were noted. After further treatment, the patient's condition worsened, and he eventually died. CONCLUSION: As the outcomes of PCI range from benign to life-threatening, an accurate diagnosis must be made to prevent unnecessary abdominal surgeries. Benign PCI in a patient without PCI correlated to underlying diseases, but received short-term corticosteroid treatment should be considered.

Increased risk of sleep apnoea among primary headache disorders: a nationwide population-based longitudinal study.

BACKGROUND: Primary headache disorders (PHDs) are associated with sleep problems. It is suggested that headache and sleep disorder share anatomical and physiological characteristics. We hypothesised that patients with PHDs were exposed to a great risk for developing sleep apnoea (SA). METHODS: In this retrospective longitudinal study, the data obtained from the Longitudinal Health Insurance Database in Taiwan were analysed. The study included 1346 patients with PHDs who were initially diagnosed and 5348 patients who were randomly selected and age/sex matched with the study group as controls. PHDs, SA, comorbidities and other confounding factors were defined based on International Classification of Diseases, Ninth Revision, Clinical Modification. Cox proportional hazards regressions were employed to examine adjusted HRs after adjusting with confounding factors. RESULTS: Our data revealed that patients with PHDs had a higher risk (HR 2.17, 95% CI 1.259 to 3.739, p<0.05) to develop SA compared with matched cohorts, whereas patients with migraine exhibited a high risk (HR 2.553, 95% CI 1.460 to 4.395, p<0.01). The results showed that patients with PHDs aged 18-44 exhibited highest risk of developing SA. In addition, males with PHDs exhibited an HR 3.159 (95% CI 1.479 to 6.749, p<0.01) for developing SA, respectively. The impact of PHDs on SA risk was progressively increased by various follow-up time intervals. CONCLUSION: Our results suggest that PHDs are linked to an increased risk for SA with sex-dependent and time-dependent characteristics.

Increased risk of non-multiple sclerosis demyelinating syndromes in patients with preexisting septicaemia: a nationwide retrospective cohort study.

BACKGROUND: Growing evidence shows links between septicaemia and non-multiple sclerosis demyelinating syndromes (NMSDS); nevertheless, epidemiological data are still very limited. This study aimed to explore the relationship between septicaemia and NMSDS in a general population. METHODS: The study included 482 781 individuals diagnosed with septicaemia and 1 892 825 age/sex-matched non-septicaemia patients for the comparison. Data were drawn from a population-based nationwide National Health Insurance Research Database Taiwan, from 1 January 2002 to 31 December 2011. The two cohorts of patients with and without septicaemia were followed up for the occurrence of NMSDS. The Cox-proportional hazard regression model was performed to estimate adjusted HR after multivariate adjustment. RESULTS: Individuals with septicaemia had a 4.17-fold (95% CI 3.21 to 5.4, p < 0.001) higher risk to develop NMSDS compared with those without septicaemia. Patients aged <65 years had a greater NMSDS risk (<45 years: HR = 6.41, 95% CI 3.65 to 11.3, p < 0.001; 45-64 years: HR = 6.66, 95% CI 3.98 to 11.2, p < 0.001). Furthermore, females with septicaemia and individuals with higher severity of septicaemia were associated with increased risks of developing NMSDS. CONCLUSIONS: Our results indicated that patients with septicaemia were likely to develop NMSDS. A possible contributing role of septicaemia in increasing the hazard of NMSDS is proposed, based on the outcome that individuals with higher severity of septicaemia carried elevated threat of encountering NMSDS.

Cubital Tunnel Syndrome Caused by Ulnar Nerve Schwannoma in a Patient with Diabetic Sensorimotor Polyneuropathy.

PURPOSE: An uncommon ulnar nerve schwannoma should not be neglected in a diabetic patient with cubital tunnel syndrome, the second most common cause of entrapment neuropathy. CASE REPORT: A 61-year-old woman with a past history of type 2 diabetes mellitus complicated with sensorimotor polyneuropathy presented with progressive numbness and weakness of the left ring and little fingers for one year. A provisional diagnosis of cubital tunnel syndrome was made according to physical examination and electrophysiological studies. The magnetic resonance imaging showed a nodular lesion over ulnar aspect of the left elbow, which was demonstrated to be a schwannoma by histopathology. The patient had moderate improvement after surgical decompression of the left cubital tunnel. CONCLUSION: This case illustrates the heterogeneous group of pathologies causing peripheral neuropathy. The diagnosis of ulnar nerve schwannoma with cubital tunnel syndrome, superimposed with diabetic sensorimotor polyneuropathy, was made carefully according to clinical manifestations as well as a series of electrophysiological, imaging, and pathological studies.

The potential impact of primary headache disorders on stroke risk.

BACKGROUND: Headache such as migraine is associated with stroke. Studies focused on primary headache disorders (PHDs) as a risk factor for stroke are limited. The purpose of this population-based cohort study was to explore whether patients with PHDs were at a high risk for developing stroke. METHODS: A total of 1346 patients with PHDs were enrolled and compared with 5384 age-, gender- and co-morbidity-matched control cohorts. International Classification of Diseases, Clinical Modification codes were administered for the definition of PHDs, stroke, and stroke risk factors. Cox proportional-hazards regressions were performed for investigating hazard ratios (HR). RESULTS: PHDs patients exhibited a 1.49 times (95% CI :1.15-1.98, p < 0.01) higher risk for developing ischaemic stroke compared with that of control cohorts. Both migraine (HR = 1.22, 95% CI :1.13-1.97, p < 0.05) and tension-type headache (HR = 2.29, 95% CI :1.22-2.80, p < 0.01) were associated with an increased risk of ischemic stroke. Females with PHDs were at greater risk of developing ischaemic stroke (HR = 1.49, 95% CI :1.13-1.90, p < 0.01) than those without PHDs. PHDs patient aged 45 to 64 years displayed significantly higher risk to develop ischaemic stroke (HR = 1.50, 95% CI: 1.11-2.10, p < 0.05) than the matched controls. The impact of PHDs on ischaemic stroke risk became gradually apparent by different following time intervals beyond 2 years after first diagnosis. CONCLUSION: PHDs is suggestive of an incremental risk for ischaemic stroke with gender-dependent, age-specific and time-dependent characteristics.

Momordicine I suppresses glioma growth by promoting apoptosis and impairing mitochondrial oxidative phosphorylation.

Glioblastoma (GBM) is the most common type of primary brain tumor. Patients with GBM have poor survival outcomes. Isolated components of Momordica charantia have anticancer effects. However, the bioactivity of M. charantia extracts against GBM remains unknown. We tested four major extracts of M. charantia and found that momordicine I reduced glioma cell viability without serious cytotoxic effects on astrocytes. Momordicine I suppressed glioma cell colony formation, proliferation, migration, and invasion. Momordicine I also induced apoptosis, intracellular reactive oxygen species (ROS) production, and senescence in glioma cells. Moreover, momordicine I decreased the oxidative phosphorylation capacity of glioma cells and inhibited tumor sphere formation in temozolomide (TMZ)-resistant GBM cells. We further explored whether the antiglioma effect of momordicine I may be related to cell cycle modulation and DLGPA5 expression. Our results indicate that the cytotoxic effect of momordicine I on glioma cells suggests its potential therapeutic application to GBM treatment. See also Figure 1(Fig. 1).

Case Report: Severe rebound after withdrawal of fingolimod in a patient with neuromyelitis optica spectrum disorder.

Purpose: Fingolimod, an oral treatment for relapsing-remitting multiple sclerosis (RRMS), has been associated with a significant rebound in disease activity after therapy cessation. We described a patient with neuromyelitis optica spectrum disorder (NMOSD) who was previously diagnosed with RRMS and experienced fatal rebound syndrome after cessation of fingolimod. Case report: A 54-year-old woman, previously diagnosed with RRMS, experienced relapse after orthopedic surgery. The diagnosis was later revised to NMOSD based on a positive aquaporin-4 antibody. Three weeks after converting the immunomodulator from fingolimod to azathioprine, severe disease reactivation was observed. Considering the multiple new and enlarging magnetic resonance imaging lesions, the temporal relationship between fingolimod cessation and symptom onset, and the relatively low possibility of disease reactivation within a short time, the diagnosis of fingolimod withdrawal syndrome was proposed. Although immediate steroid pulse therapy and plasma exchange were performed, the patient eventually died owing to a fulminant clinical course. Conclusion: Fingolimod withdrawal syndrome is well known in patients with multiple sclerosis (MS). It can also occur in patients with NMOSD. Recognizing patients with NMOSD who present with MS-like manifestations, and avoiding drugs that may be harmful to patients with NMOSD, are important.

The 2023 Taiwan Stroke Society Guidelines for the management of patients with intracranial atherosclerotic disease.

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke, especially in Asian populations, which has a high risk of recurrent stroke and cardiovascular comorbidities. The present guidelines aim to provide updated evidence-based recommendations for diagnosis and management of patients with ICAD. Taiwan Stroke Society guideline consensus group developed recommendations for management of patients with ICAD via consensus meetings based on updated evidences. Each proposed class of recommendation and level of evidence was approved by all members of the group. The guidelines cover six topics, including (1) epidemiology and diagnostic evaluation of ICAD, (2) nonpharmacological management of ICAD, (3) medical therapy for symptomatic ICAD, (4) endovascular thrombectomy and rescue therapy for acute ischemic stroke with underlying ICAD, (5) endovascular interventional therapy for postacute symptomatic intracranial arterial stenosis, and (6) surgical treatment of chronic symptomatic intracranial arterial stenosis. Intensive medical treatment including antiplatelet therapy, risk factor control, and life style modification are essential for patients with ICAD.

A Metallomic Approach to Assess Associations of Plasma Metal Levels with Amnestic Mild Cognitive Impairment and Alzheimer's Disease: An Exploratory Study.

Alzheimer's disease (AD) involves the abnormal activity of transition metals and metal ion dyshomeostasis; however, the potential of trace metal biomarkers in predicting cognitive decline has not been evaluated. This study aimed to assess the potential of 36 trace elements in predicting cognitive decline in patients with amnestic mild cognitive impairment (aMCI) or AD. Participants (9 controls, 23 aMCI due to AD, and 8 AD dementia) underwent comprehensive cognitive tests, including the Mini-Mental State Examination (MMSE) and trace metal analysis. The correlations between the plasma trace element levels and annual MMSE changes during follow-up were analyzed. We found that an increase in disease severity was linked to lower plasma levels of boron (B), bismuth (Bi), thorium (Th), and uranium (U) (adjusted p < 0.05). Higher baseline calcium levels (r = 0.50, p = 0.026) were associated with less annual cognitive decline; those of B (r = −0.70, p = 0.001), zirconium (r = −0.58, p = 0.007), and Th (r = −0.52, p = 0.020) with rapid annual cognitive decline in the aMCI group; and those of manganese (r = −0.91, p = 0.035) with rapid annual cognitive decline in the AD group. Overall, our exploratory study suggests that plasma metal levels have great potential as in vivo biomarkers for aMCI and AD. Larger sample studies are necessary to confirm these results.

Case report: Vaccine-induced immune thrombotic thrombocytopenia complicated by acute cerebral venous thrombosis and hemorrhage after AstraZeneca vaccines followed by Moderna COVID-19 vaccine booster and surgery.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a well-known complication of adenoviral vector COVID-19 vaccines including ChAdOx1 nCoV-19 (AstraZeneca) and Ad26. COV2.S (Janssen, Johnson & Johnson). To date, only a few cases of mRNA COVID-19 vaccine such as mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech)-induced VITT have been reported. We report a case of VITT with acute cerebral venous thrombosis and hemorrhage after a booster of mRNA-1273 (Moderna) vaccine in a patient previously vaccinated with two doses of the AstraZeneca vaccine. A 42-year-old woman presented with sudden onset of weakness of the right upper limb with focal seizure. She had received two doses of AstraZeneca vaccines and a booster with Moderna vaccine 32 days before presentation. She had also undergone a laparoscopic myomectomy 12 days previously. Laboratory examinations revealed anemia (9.5 g/dl), thrombocytopenia (31 × 103/µl), and markedly elevated d-dimer (>20.0 mg/L; reference value < 0.5 mg/L). The initial brain computed tomography (CT) was normal, but a repeated scan 10 h later revealed hemorrhage at the left cerebrum. Before the results of the blood smear were received, on suspicion of thrombotic microangiopathy with thrombocytopenia and thrombosis, plasmapheresis and pulse steroid therapy were initiated, followed by intravenous immunoglobulin (1 g/kg/day for two consecutive days) due to refractory thrombocytopenia. VITT was confirmed by positive anti-PF4 antibody and both heparin-induced and PF4-induced platelet activation testing. Clinicians should be aware that mRNA-1273 Moderna, an mRNA-based vaccine, may be associated with VITT with catastrophic complications. Additionally, prior exposure to the AstraZeneca vaccine and surgical procedure could also have precipitated or aggravated autoimmune heparin-induced thrombocytopenia/VITT-like presentation.

The optimal pulse pressures for healthy adults with different ages and sexes correlate with cardiovascular health metrics.

Background: Pulse pressure (PP) may play a role in the development of cardiovascular disease, and the optimal PP for different ages and sexes is unknown. In a prospective cohort, we studied subjects with favorable cardiovascular health (CVH), proposed the mean PP as the optimal PP values, and demonstrated its relationship with healthy lifestyles. Methods and results: Between 1996 and 2016, a total of 162,636 participants (aged 20 years or above; mean age 34.9 years; 26.4% male subjects; meeting criteria for favorable health) were recruited for a medical examination program. PP in male subjects was 45.6 ± 9.4 mmHg and increased after the age of 50 years. PP in female subjects was 41.8 ± 9.5 mmHg and increased after the age of 40 years, exceeding that of male subjects after the age of 50 years. Except for female subjects with a PP of 40-70 mmHg, PP increase correlates with both systolic blood pressure (BP) increase and diastolic BP decrease. Individuals with mean PP values are more likely to meet health metrics, including body mass index (BMI) <25 kg/m2 (chi-squared = 9.35, p<0.01 in male subjects; chi-squared = 208.79, p < 0.001 in female subjects) and BP <120/80 mmHg (chi-squared =1,300, p < 0.001 in male subjects; chi-squared =11,000, p < 0.001 in female subjects). We propose a health score (Hscore) based on the sum of five metrics (BP, BMI, being physically active, non-smoking, and healthy diet), which significantly correlates with the optimal PP. Conclusion: The mean PP (within ±1 standard deviation) could be proposed as the optimal PP in the adult population with favorable CVH. The relationship between health metrics and the optimal PP based on age and sex was further demonstrated to validate the Hscore.

Use of Hormone Replacement Therapy and Risk of Dementia: A Nationwide Cohort Study.

OBJECTIVE: Estrogen has the potential to influence brain physiology implicated in dementia pathogenesis. Hormone replacement therapy (HRT) might be expected to influence the risk of dementia. Observational data indicated that HRT was associated with reductions in dementia risk, but experimental evidence demonstrates that HRT increases the incidence of dementia. To determine the effect of HRT on risk of dementia, a retrospective cohort study was performed using a nationwide claims dataset in Taiwan. METHODS: A population-base longitudinal study was performed using data from the Longitudinal Health Insurance Database in Taiwan. A total of 35,024 women with HRT were enrolled as the exposed cohort and 70,048 women without HRT were selected on the basis of propensity matching as the comparison cohort. All of the subjects were followed up until the diagnosis of dementia, death, or at the end of December 31, 2013, whichever occurred first. Overall, the average duration of follow-up (±SD) in the HT and comparison cohort was 12.3(±2.3) and 12.2 (±2.4), respectively. The Cox proportional hazards regression models were conducted to produce hazard ratios (HRs) with 95% confidence intervals (CIs) to evaluate the association of HRT with the risk of dementia. RESULTS: In the follow-up period, the cumulative incidence of dementia for the HRT cohort (20.04 per 1,000) was significantly higher than the corresponding cumulative incidence for the comparison cohort (15.79 per 1,000), resulting in an adjusted hazard ratio of 1.35 (95% CI, 1.13-2.62). There was an increased risk of dementia with a higher cumulative dose of HRT prescription (p for trend <0.0001). CONCLUSION: This cohort study documented that HRT was associated with an increased risk of dementia. The clinical implications of this study merit further investigations.

Increased risk of sleep-related movement disorder in patients with Helicobacter pylori infection: A nationwide population-based study.

Background and purpose: Evidence increasingly suggests that Helicobacter pylori infection (HPI) is associated with movement disorders such as Parkinson's disease (PD). However, the relationship between HPI and sleep-related movement disorders (SRMD) remains unknown. This nationwide population-based study tried to demonstrate whether patients with HPI have a higher risk of developing SRMD in a general adult population. Methods: The study cohort enrolled 9,393 patients who were initially diagnosed with HPI between 2000 and 2013. Notably, 37,572 age- and sex-matched controls without prior HPI were selected as the reference. A Cox proportional hazard regression analysis was performed for multivariate adjustment. Results: Patients with HPI had a higher risk of developing SRMD (adjusted hazard ratio [HR] = 2.18, 95% confidence interval [CI] = 1.26-3.82, p < 0.01). Patients with HPI aged ≥65 years exhibited the highest risk (HR = 3.01, 95% CI = 1.90-5.30, p < 0.001), followed by patients aged 45-64 years (HR = 1.69, 95% CI = 1.26-2.90, p <0.01) and <45 years (HR = 1.49, 95% CI = 1.12-2.49, p < 0.01). Patients were most likely to develop SRMD 5 years or more after diagnosis of HPI (HR = 3.33, 95% CI = 1.97-5.89, p < 0.001). The increased risk of SRMD in male patients with HPI (HR = 2.73, 95% CI = 1.53-4.79, p < 0.001) was greater than in female patients (HR = 1.14, 95% CI = 1.04-1.65, p < 0.05). Conclusion: Patients with HPI were associated with an increased risk for SRMD, with a higher risk in men, aged ≥65 years, and diagnosed for more than 5 years.

Characterization of gene expression changes in human neural stem cells and endothelial cells modeling a neurovascular microenvironment.

Angiogenesis-mediated neovascularization correlates with recovery after intracerebral implantation of neural stem cells (NSCs) in stroke. To elucidate NSCs' mechanism of action, it is essential to understand how these interact with the brain's vasculature after implantation. Using an all-human endothelial cell (EC, D3 cell line) and NSC (STROC05 and CTXOE03) co-culture model, fluorescently activated cell sorting (FACS) was used to isolate each cell type for a comparison of gene expression between monocultures of undifferentiated proliferating and differentiated non-proliferating cells. Gene expression for angiogenic factors (vascular endothelial growth factor, platelet derived growth factor, angiopoietin), as well as cell survival (brain derived neurotrophic factor, fibroblast growth factor) and migration (stromal cell-derived factor-1a) were measured and contrasted with the corresponding receptors on each cell type. The cellular source of extracellular matrix defining the basement membrane (vitronectin, fibronectin, laminin, collagen I and IV) and neuropil (hyaluronic acid, aggrecan, neurocan, thrombospondin, nidogen and brain associated link protein-1) was evaluated for NSCs and ECs. Co-culturing dramatically changed the expression profiles of each cell type in comparison to undifferentiated, but also differentiated cells. These results indicate that monocultures provide a poor model to investigate the cellular signaling involved in a tissue repair response. Co-cultures of NSCs and ECs forming vasculature-like structures (VLS) provide a more complex model to investigate NSC-induced neovascularization. These in vitro studies are essential to tease out individual cell signaling in NSCs and ECs to develop a mechanistic understanding of the efficacy of NSCs as a therapeutic for stroke.

Female reproductive health and cognitive function.

OBJECTIVE: The impact of sex hormones milieu on women's cognitive performance at different reproductive stages has caused increased caution. Our research aims to explore whether parity is negatively correlated with cognitive function. METHODS: There were 1,093 postmenopausal participants recruited from the Health and Nutrition Examination Survey dataset. Cognitive functioning was evaluated by digit symbol substitution test (DSST). We performed log transformation to normalize the distributions of the DSST values. RESULTS: Participants were categorized into tertile groups based on the number of pregnancies. Using the zero to one pregnancy group as the reference, there was a reduced DSST scores with ß values of -0.13 (95% confidence interval [CI] -0.23 to -0.03; P = 0.008) in the ≥5 pregnancies group after adjusting for socioeconomic, medical disease, lifestyle, and reproductive components. Moreover, women who had their last pregnancy after 28 years old and education less than 12 years also was correlate with cognitive malfunction after adjusting relevant covariates (both P < 0.001). CONCLUSIONS: Women with at least five pregnancies had poorer cognitive performance. Last pregnancy after 28 years old and education less than 12 years also was associated with poorer DSST scores. VIDEO SUMMARY:: http://links.lww.com/MENO/A634.

http://links.lww.com/MENO/A634.