Gender Differences in the Protective Role of Grandparenting in Dementia Risk.

OBJECTIVES: This study provides one of the first national longitudinal studies of the association between caring for grandchildren (i.e., grandparenting) and the risk of dementia in the United States, with a focus on gender-specific variations. METHODS: We estimated discrete-time event history models, drawing upon data from the Health and Retirement Study (2000-2016). The analytic sample included 10,217 community-dwelling White and Black grandparents aged 52 years and older at baseline. RESULTS: Noncoresident grandparenting was associated with a lower risk of dementia for both women and men compared to grandparents who did not take care of grandchildren. However, the cognitive advantage showed different patterns based on gender and the combination of care intensity and family structure. Grandmothers had a lower risk of dementia than noncaregiving grandmothers when providing a light level of noncoresident grandparenting, whereas grandfathers who provided intensive noncoresident grandparenting had a reduced risk of dementia compared to their noncaregiving counterparts. Grandparenting experiences within multigenerational households and skipped-generation households were not associated with dementia risk. DISCUSSION: Intergenerational caregiving plays a pivotal role in shaping cognitive health during later life; however, the impact is nuanced, depending on factors such as gender, care intensity, and family structure.

Substantially Accelerated Response and Recovery in Pd-Decorated WO3 Nanorods Gasochromic Hydrogen Sensor.

The development of hydrogen (H2) gas sensors is essential for the safe and efficient adoption of H2 gas as a clean, renewable energy source in the challenges against climate change, given its flammability and associated safety risks. Among various H2 sensors, gasochromic sensors have attracted great interest due to their highly intuitive and low power operation, but slow kinetics, especially slow recovery rate limited its further practical application. This study introduces Pd-decorated amorphous WO3 nanorods (Pd-WO3 NRs) as an innovative gasochromic H2 sensor, demonstrating rapid and highly reversible color changes for H2 detection. In specific, the amorphous nanostructure exhibits notable porosity, enabling rapid detection and recovery by facilitating effective H2 gas interaction and efficient diffusion of hydrogen ions (H+) dissociated from the Pd nanoparticles (Pd NPs). The optimized Pd-WO3 NRs sensor achieves an impressive response time of 14 s and a recovery time of 1 s to 5% H2. The impressively fast recovery time of 1 s is observed under a wide range of H2 concentrations (0.2-5%), making this study a fundamental solution to the challenged slow recovery of gasochromic H2 sensors.

Neighborhood Features and Cognitive Function: Moderating Roles of Individual Socioeconomic Status.

INTRODUCTION: There is an interest in exploring the associations between neighborhood characteristics and individual cognitive function; however, little is known about whether these relationships can be modified by individual socioeconomic status, such as educational attainment and income. METHODS: Drawing from the 2010-2018 Health and Retirement Study, this study analyzed 10,621 older respondents (aged 65+) with a total of 33,931 person-waves. These respondents did not have dementia in 2010 and stayed in the same neighborhood throughout the study period. Cognitive function was measured with a 27-point indicator biennially, and neighborhood characteristics (i.e., walkability, concentrated disadvantage, and social isolation) were assessed in 2010. All analyses were performed in 2023. RESULTS: Cognitive function is positively associated with neighborhood walkability and negatively related to concentrated disadvantage, suggesting that exposures to these neighborhood characteristics have long-lasting impacts on cognitive function. Furthermore, individual socioeconomic status modifies the relationship between neighborhood characteristics and cognitive function. Compared with those graduating from college, respondents without a bachelor's degree consistently have lower cognitive function but the educational gap in cognitive function narrows with increases in walkability (b= -0.152, SE=0.092), and widens when neighborhood concentrated disadvantage (b=0.212, SE=0.070) or social isolation (b=0.315, SE=0.125) rises. The income gap in cognitive function shrinks with increases in walkability (b= -0.063, SE=0.027). CONCLUSIONS: The moderating role of socioeconomic status indicates that low-socioeconomic status older adults who also live in disadvantaged neighborhoods face a higher risk of poor cognitive function. Low-education and low-income aging adults may have the most to gain from investments to improve neighborhood characteristics.

Risk factor analyses of contrast leakage and contrast-induced encephalopathy following coil embolization for unruptured intracranial aneurysm.

BACKGROUND: Contrast-induced encephalopathy (CIE) following endovascular interventions is a rare but serious complication. This study aimed to investigate the risk factors of contrast leakage (CL) and CIE in patients who underwent coil embolization of unruptured intracranial aneurysms (UIAs). METHODS: Patients with UIAs who underwent coil embolization at a single tertiary institute between January 2019 and January 2022 were enrolled retrospectively. CL was defined as cortical or subcortical contrast enhancement with effacement of the cortical sulci. CIE was defined as the new onset of neurological deficits associated with CL. Following the procedure, all patients underwent CT scans, and MRI scans were performed on those with symptoms. Patient and procedural risk factors were investigated. RESULTS: In total, 459 patients were analyzed. The median procedure time and contrast dose were 69 min and 96 mL, respectively. CL was evident in 35 patients. In the multivariate analysis, hypertension, large aneurysm, longer procedure time, and greater contrast dose were associated with CL. CIE was diagnosed in 19 patients, and the risk factors included large aneurysm, longer procedure time, and greater contrast dose. The procedure time was predictive of both CL (P<0.001) and CIE (P=0.01). The optimal cut-off value for procedure time was 81.5 min. All CIE patients recovered completely within 8-96 hours. CONCLUSIONS: A large aneurysm and prolonged procedure time may increase the patient's risk of CL and CIE due to increased contrast exposure. Patients who underwent a procedure that exceeded 1.5 hours necessitate post-procedure evaluation and monitoring.

Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma.

Background: The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification. Methods: In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005-2018) and an external validation site in South Korea (44 patients, 2013-2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines. Results: The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64-11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients. Conclusions: The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer.

A multicenter, phase II trial of GC1118, a novel anti-EGFR antibody, for recurrent glioblastoma patients with EGFR amplification.

BACKGROUND: We evaluated the therapeutic efficacy of GC1118, a novel anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification. METHODS: This study was a multicenter, open-label, single-arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells. GC1118 was administered intravenously at a dose of 4 mg/kg once weekly. The primary endpoint was the 6-month progression-free survival rate (PFS6). Next-generation sequencing was performed to investigate the molecular biomarkers related to the response to GC1118. RESULTS: Between April 2018 and December 2020, 21 patients were enrolled in the study and received GC1118 treatment. Eighteen patients were eligible for efficacy analysis. The PFS6 was 5.6% (95% confidence interval, 0.3%-25.8%, Wilson method). The median progression-free survival was 1.7 months (range: 28 days-7.2 months) and median overall survival was 5.7 months (range: 2-22.0 months). GC1118 was well tolerated except skin toxicities. Skin rash was the most frequent adverse event and four patients experienced Grade 3 skin-related toxicity. Genomic analysis revealed that the immune-related signatures were upregulated in patients with tumor regression. CONCLUSION: This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune-mediated antitumor efficacy of GC1118.

Radiation therapy promotes unsaturated fatty acids to maintain survival of glioblastoma.

Radiation therapy (RT) is essential for the management of glioblastoma (GBM). However, GBM frequently relapses within the irradiated margins, thus suggesting that RT might stimulate mechanisms of resistance that limits its efficacy. GBM is recognized for its metabolic plasticity, but whether RT-induced resistance relies on metabolic adaptation remains unclear. Here, we show in vitro and in vivo that irradiated GBM tumors switch their metabolic program to accumulate lipids, especially unsaturated fatty acids. This resulted in an increased formation of lipid droplets to prevent endoplasmic reticulum (ER) stress. The reduction of lipid accumulation with genetic suppression and pharmacological inhibition of the fatty acid synthase (FASN), one of the main lipogenic enzymes, leads to mitochondrial dysfunction and increased apoptosis of irradiated GBM cells. Combination of FASN inhibition with focal RT improved the median survival of GBM-bearing mice. Supporting the translational value of these findings, retrospective analysis of the GLASS consortium dataset of matched GBM patients revealed an enrichment in lipid metabolism signature in recurrent GBM compared to primary. Overall, these results demonstrate that RT drives GBM resistance by generating a lipogenic environment permissive to GBM survival. Targeting lipid metabolism might be required to develop more effective anti-GBM strategies.

Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild-type primary glioblastoma.

BACKGROUND: Although temozolomide (TMZ) has been used as a standard adjuvant chemotherapeutic agent for primary glioblastoma (GBM), treating isocitrate dehydrogenase wild-type (IDH-wt) cases remains challenging due to intrinsic and acquired drug resistance. Therefore, elucidation of the molecular mechanisms of TMZ resistance is critical for its precision application. METHODS: We stratified 69 primary IDH-wt GBM patients into TMZ-resistant (n = 29) and sensitive (n = 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy. RESULTS: In vitro TMZ sensitivity of patient-derived GSCs classified patients into groups with different survival outcomes (P = 1.12e-4 for progression-free survival (PFS) and 3.63e-4 for overall survival (OS)). Moreover, we found that elevated gene expression of EGR4, PAPPA, LRRC3, and ANXA3 was associated to intrinsic TMZ resistance. In addition, other features such as 5-aminolevulinic acid negative, mesenchymal/proneural expression subtypes, and hypermutation phenomena were prone to promote TMZ resistance. In contrast, concurrent copy-number-alteration in PTEN, EGFR, and CDKN2A/B was more frequent in TMZ-sensitive samples (Fisher's exact P = 0.0102), subsequently consolidated by multi-sector sequencing analyses. Integrating all features, we trained a ML tool to segregate TMZ-resistant and sensitive groups. Notably, our method segregated IDH-wt GBM patients from The Cancer Genome Atlas (TCGA) into two groups with divergent survival outcomes (P = 4.58e-4 for PFS and 3.66e-4 for OS). Furthermore, we showed a highly heterogeneous TMZ-response pattern within each GBM patient using in vitro TMZ screening and genomic characterization of multisector GSCs. Lastly, the prediction model that evaluates the TMZ efficacy for primary IDH-wt GBMs was developed into a webserver for public usage ( http://www.wang-lab-hkust.com:3838/TMZEP ). CONCLUSIONS: We identified molecular characteristics associated to TMZ sensitivity, and illustrate the potential clinical value of a ML model trained from pharmacogenomic profiling of patient-derived GSC against IDH-wt GBMs.

An agonistic anti-Tie2 antibody suppresses the normal-to-tumor vascular transition in the glioblastoma invasion zone.

Tumor progression is intimately associated with the vasculature, as tumor proliferation induces angiogenesis and tumor cells metastasize to distant organs via blood vessels. However, whether tumor invasion is associated with blood vessels remains unknown. As glioblastoma (GBM) is featured by aggressive invasion and vascular abnormalities, we characterized the onset of vascular remodeling in the diffuse tumor infiltrating zone by establishing new spontaneous GBM models with robust invasion capacity. Normal brain vessels underwent a gradual transition to severely impaired tumor vessels at the GBM periphery over several days. Increasing vasodilation from the tumor periphery to the tumor core was also found in human GBM. The levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) showed a spatial correlation with the extent of vascular abnormalities spanning the tumor-invading zone. Blockade of VEGFR2 suppressed vascular remodeling at the tumor periphery, confirming the role of VEGF-VEGFR2 signaling in the invasion-associated vascular transition. As angiopoietin-2 (ANGPT2) was expressed in only a portion of the central tumor vessels, we developed a ligand-independent tunica interna endothelial cell kinase 2 (Tie2)-activating antibody that can result in Tie2 phosphorylation in vivo. This agonistic anti-Tie2 antibody effectively normalized the vasculature in both the tumor periphery and tumor center, similar to the effects of VEGFR2 blockade. Mechanistically, this antibody-based Tie2 activation induced VE-PTP-mediated VEGFR2 dephosphorylation in vivo. Thus, our study reveals that the normal-to-tumor vascular transition is spatiotemporally associated with GBM invasion and may be controlled by Tie2 activation via a novel mechanism of action.

Characteristics and Predictors of Sleep Among Spousal Care Dyads Living With Chronic Conditions.

OBJECTIVES: Poor sleep is common among older adults with chronic health conditions and their spousal caregivers. However, dyadic sleep patterns among spouses are underexplored within the literature. This study examines dyadic sleep characteristics and associated contextual factors among spousal care dyads. METHODS: Participants included 462 older adult spousal care dyads from the 2015 National Health and Aging Trends Study and National Study of Caregiving (mean ages of care recipients/caregivers = 79 and 76 years, respectively; 22% of dyads were living with dementia). Self-reported sleep included frequency of (a) trouble falling back asleep among dyads, (b) care-related sleep disturbances among caregivers, and (c) trouble initiating sleep among care recipients. Predictors included between-dyad characteristics such as whether respondents had dementia, care burden and support, relationship quality, neighborhood cohesion, and within-dyad characteristics such as demographics, depression, and positive affect. We conducted multilevel dyadic analysis and actor-partner interdependence modeling. RESULTS: Sleep was correlated more among dyads living with dementia than those with other chronic conditions. Care dyads had poorer sleep if caregivers reported higher care burden; however, better relationship quality marginally ameliorated the association. Depressive symptoms had a partner effect on poorer sleep among care dyads, whereas positive emotions and older age only had an actor effect on better sleep for care recipients and spousal caregivers. Neighborhood cohesion, care support, and other demographic characteristics were not associated with dyadic sleep outcomes. DISCUSSION: Addressing both care recipient- and caregiver-related factors may improve sleep health for both members of the care dyad living with chronic conditions.

Oxicam-type nonsteroidal anti-inflammatory drugs enhance Agrobacterium-mediated transient transformation in plants.

Agrobacterium-mediated transformation is a key innovation for plant breeding, and routinely used in basic researches and applied biology. However, the transformation efficiency is often the limiting factor of this technique. In this study, we discovered that oxicam-type nonsteroidal anti-inflammatory drugs, including tenoxicam (TNX), increase the efficiency of Agrobacterium-mediated transient transformation. TNX treatment increased the transformation efficiency of Agrobacterium-mediated transformation of Arabidopsis thaliana mature leaves by agroinfiltration. The increase of efficiency by TNX treatment was not observed in dde2/ein2/pad4/sid2 quadruple mutant, indicating that TNX inhibits the immune system mediated by jasmonic acid, ethylene, and salicylic acid against to Agrobacterium. We also found that TNX-treatment is applicable for the transient expression and subcellular localization analysis of fluorescent-tagged proteins in Arabidopsis leaf cells. In addition, we found that TNX increases the efficiency of Agrobacterium-mediated transient transformation of Jatropha. Given that treatment with oxicam compounds is a simple and cost effective method, our findings will provide a new option to overcome limitations associated with Agrobacterium-mediated transformation of various plant species.

Rotational Vertebral Artery Syndrome (Bow Hunter's Syndrome): A Rare Differential Diagnosis in Patients With Syncope.

Syncope is a common symptom in clinical practice. Rotational vertebral artery occlusion syndrome, also referred to as Bow Hunter's syndrome (BHS), is a rare condition associated with syncope and is caused by mechanical occlusion or stenosis secondary to mechanical compression of the vertebral artery during head rotation. BHS is associated with a multifactorial etiology; however, in most cases, this condition is attributed to degenerative changes. A 53-year-old man visited our hospital for the evaluation of fainting and dizziness episodes that occurred when he turned his head. Evaluation as an outpatient in the Department of Neurology showed a positive result on the Frenzel goggle test. Transfemoral cerebral angiography performed at the Department of Neurosurgery revealed stenosis of the proximal right vertebral artery. Complete occlusion of the vertebral artery was observed, and the head was turned to the right. Decompression and fusion were performed, and the contributory lesion was completely removed. Postoperative imaging confirmed complete removal of the spur and sufficient vertebral artery decompression; the patient's symptoms resolved postoperatively.

Multiscale dimensions of county-level disparities in opioid use disorder rates among older Medicare beneficiaries.

Background: Opioid use disorder (OUD) among older adults (age ≥ 65) is a growing yet underexplored public health concern and previous research has mainly assumed that the spatial process underlying geographic patterns of population health outcomes is constant across space. This study is among the first to apply a local modeling perspective to examine the geographic disparity in county-level OUD rates among older Medicare beneficiaries and the spatial non-stationarity in the relationships between determinants and OUD rates. Methods: Data are from a variety of national sources including the Centers for Medicare & Medicaid Services beneficiary-level data from 2020 aggregated to the county-level and county-equivalents, and the 2016-2020 American Community Survey (ACS) 5-year estimates for 3,108 contiguous US counties. We use multiscale geographically weighted regression to investigate three dimensions of spatial process, namely "level of influence" (the percentage of older Medicare beneficiaries affected by a certain determinant), "scalability" (the spatial process of a determinant as global, regional, or local), and "specificity" (the determinant that has the strongest association with the OUD rate). Results: The results indicate great spatial heterogeneity in the distribution of OUD rates. Beneficiaries' characteristics, including the average age, racial/ethnic composition, and the average hierarchical condition categories (HCC) score, play important roles in shaping OUD rates as they are identified as primary influencers (impacting more than 50% of the population) and the most dominant determinants in US counties. Moreover, the percentage of non-Hispanic white beneficiaries, average number of mental health conditions, and the average HCC score demonstrate spatial non-stationarity in their associations with the OUD rates, suggesting that these variables are more important in some counties than others. Conclusions: Our findings highlight the importance of a local perspective in addressing the geographic disparity in OUD rates among older adults. Interventions that aim to reduce OUD rates in US counties may adopt a place-based approach, which could consider the local needs and differential scales of spatial process.

Treatment results of anterior choroidal artery aneurysms treated mostly with coil embolization: A single-center experience.

BACKGROUND: Anterior choroidal artery (AchA) aneurysms are usually small in diameter because of the size of the involved artery and are often wide-necked. Coil embolization of AchA aneurysm is thus challenging because of serious risks, such as thromboembolic occlusion of artery and perforation of aneurysm dome. Therefore, aneurysmal neck clipping remains widely performed despite a recent increase in the use of coil embolization for aneurysm treatment. We report the treatment results of AchA aneurysms mostly (92.3%) treated with coil embolization at our institute. METHODS: The database and medical records of patients who underwent coil embolization for AchA aneurysms were retrospectively analyzed. The clinical and imaging results and procedure-related complications were investigated after coil embolization performed between January 2006 and March 2022 at our institute. RESULTS: In total, 96 AchA aneurysms comprising 65 unruptured and 31 ruptured aneurysms, including only 1 ruptured aneurysm (1.0%) re-embolized at postoperative day 192 because of coil compaction, were evaluated. After the initial coil embolization, complete occlusion was attained in 41, residual neck in 45, and residual aneurysm in 10 patients. Follow-up radiological studies after 6-174 months were performed for 80 aneurysms. Complete occlusion was noted in 57 patients, residual neck in 22, and residual aneurysm in 1. The dysarthria experienced by one (1.0%) patient was the only symptomatic procedure-related complication. After coil embolization, neither delayed new rupture nor re-rupture was observed. CONCLUSIONS: The results of this study demonstrate that coil embolization is a safe and effective treatment option for patients with AchA aneurysms.

A Huge Radiation-Induced Cavernous Hemangioma Following Stereotactic Radiosurgery for Meningioma: A Case Report.

Radiation-induced cavernous hemangiomas (RICHs) have been increasingly reported as a late complication after conventional radiotherapy. RICH after stereotactic radiosurgery (SRS) is extremely rare and the few cases have been reported to demonstrate their properties. A 72-year-old female patient presented with progressive neurologic deficits. She underwent tumor surgery for meningioma 13 years ago and two times of SRS for treating a residual tumor. Newly-developed mass was 4.3 cm-sized heterogeneously enhancing mass with severe cerebral edema. She underwent surgical resection and the histologic examinations revealed organized hematoma. Finally, it was diagnosed as a RICH following SRS based on radiological and histological findings and a history of multiple radiosurgeries. Clinical, radiological, and histological features of a RICH following SRS were discussed in this report.

A Deep Neural Network-Based Model Predicting Peritumoral Edema After Radiosurgery for Meningioma.

BACKGROUND: Gamma Knife radiosurgery (GKS) is a promising treatment option for meningioma. However, the incidence of peritumoral edema (PTE) following GKS has been reported to be 7%-38%. This study aimed to develop a predictive model for post-GKS PTE using a deep neural network (DNN) algorithm. METHODS: Patients treated with GKS for meningioma between November 2012 and February 2020 at a single tertiary center were reviewed. The primary outcome was newly developed or aggravated PTE after GKS. Clinical data, including radiosurgical parameters, were collected, and imaging data obtained at the time of GKS were incorporated into the model using a 50-layered residual neural network, ResNet50. Consequently, the model efficiency was evaluated considering the accuracy and area under the receiver operating curve (AUC) values. RESULTS: A total of 202 patients were included in this study. The median tumor volume was 2.3 mL, and the median prescription dose was 13 Gy. PTE was observed before GKS in 22 patients. Post-GKS PTE was evident in 28 patients (13.9%), which further evolved to radiation necrosis in 5 patients. The accuracy and AUC values of the hybrid data model based on both clinical and imaging data were 0.725 and 0.701, respectively. The performance of the hybrid data model was superior to that of the other models based on clinical or image data only. CONCLUSIONS: The DNN-based model using both clinical and imaging data exhibited fair results in predicting post-GKS PTE in meningioma treatment. Predictive models using imaging data may be helpful in prognostic research.

Reverse Trans-Sellar Neuroendoscopic Management of a Large Rathke's Cleft Cyst Causing Obstructive Hydrocephalus: A Case Report.

Symptomatic Rathke's cleft cysts (RCCs) can be treated by surgical procedures, usually through an endonasal transsphenoidal corridor using either a microscope or an endoscope. We report a large suprasellar extended RCC causing obstructive hydrocephalus, which was efficiently managed by a novel surgical route named "reverse" trans-sellar approach using transventricular neuroendoscopy. A 48-year-old woman complained of persistent headache and a tendency to fall that had begun 6 months previously. The images obtained from MRI scan showed intra- and supra-sellar cystic masses occupying the third ventricle with obstruction of the foramina of Monro and the aqueduct of Sylvius. The cystic wall showed a slight enhancement, and the cystic contents showed iso-signal intensity on T1-and T2-weighted images. Instead of trans-nasal trans-sellar surgery, we decided to operate using a conventional transventricular endoscope. A thin cystic capsule, which blocked the foramina of Monro and the aqueduct of Sylvius, was fenestrated and removed and a third ventriculostomy was performed. The defect in the infundibulum between sellar and suprasellar cysts was widened and used as a corridor to drain cystic contents (reverse trans-sellar route). The final pathological finding revealed an RCC with focal metaplasia. We efficiently managed a large RCC by transventricular neuroendoscopic surgery with cyst fenestration and third ventriculostomy and simultaneously drained the sellar contents using a novel surgical route. Reverse trans-sellar neuroendoscopic surgery is a relevant treatment option for selective patients with large suprasellar extensions of RCCs.

A flare of Still's disease following COVID-19 vaccination in a 34-year-old patient.

Vaccination is a cornerstone for reducing the risk of COVID-19 infection during a pandemic. Although the currently used COVID-19 vaccine is considered safe, some concerns persist regarding the likelihood of flares of rheumatic diseases. Still's disease is a rare auto-inflammatory disorder of unknown etiology, and the data on the flare of Still's disease following COVID-19 vaccination are limited. Therefore, we hereby present the case of a 34-year-old female patient with Still's disease who experienced a flare after a ChAdOx1 nCoV-19 vaccination. The patient visited the emergency department complaining of fever, arthralgia, myalgia, pleuritic chest pain and macular salmon-pink rash on her back for the past 2 days. She had maintained low Still's disease activity with etanercept and low-dose glucocorticoid for 14 years. She received the ChAdOx1 nCoV-19 vaccine 7 days before the flare. Laboratory investigations revealed leucocytosis and elevated serum levels of erythrocyte sedimentation rate, C-reactive protein, and ferritin. Computed tomography showed no specific findings. She received methylprednisolone pulse therapy, etanercept, and methotrexate for treating the Still's disease flare. However, her symptoms were not fully controlled, and she developed pericarditis, pleuritis, fever and macular rashes expanding to her extremities. After excluding infectious conditions by blood culture and pleural fluid analysis, we administered tocilizumab with methotrexate and prednisolone. Her symptoms and laboratory findings improved significantly, and she was discharged without symptoms 7 days later. Although rare, this case of a patient with Still's disease undergoing a flare following vaccination suggests that close observation of disease activity is warranted following COVID-19 vaccination.

Oxicam-type non-steroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including salicylic acid (SA), target mammalian cyclooxygenases. In plants, SA is a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identify that the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent plant immune response. TNX treatment decreases NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. A cysteine labeling assay reveals that cysteine residues in NPR1 can be oxidized in vitro, leading to disulfide-bridged oligomerization of NPR1, but not in vivo regardless of SA or TNX treatment. Therefore, this study indicates that oxicam inhibits NPR1-mediated SA signaling without affecting the redox status of NPR1.

Caring as curing: Grandparenting and depressive symptoms in China.

Research on grandparenting (i.e., caring for grandchildren) and mental health in Asian contexts has been limited, despite the rapid growth of older adults who take care of grandchildren. This study aims to investigate how grandparenting influences depressive symptoms in China. Using the China Health and Retirement Longitudinal Study (2011-2015, N = 4354), we conducted fixed effects regression models to examine the association between various types of grandparenting and depressive symptoms among older adults between the ages of 45 and 80. The results show that for grandparents, providing care to their grandchildren in skipped-generation households (i.e., grandparent-grandchildren families without adult children) is associated with a lower level of depressive symptoms compared to providing no care, after controlling for socioeconomic status, health behaviors, social support, and basic demographic characteristics. Other types of care (i.e., multigenerational household grandparenting, and part-time and full-time noncoresident grandparenting) are not significantly linked to caregiving grandparents' depressive symptoms. Overall, our findings suggest that sociocultural contexts need to be considered in explaining the different mental health implications of grandparenting.