Oligodendrocytes (OLs) are brain cells that make myelin, the insulating sheath that supports nerve signal transmission. Although oligodendrocyte dysfunction is common in the central nervous system (CNS), how these cells respond to injury remains incompletely understood. Here we show, using mouse models and mouse tissue analyses, that OLs respond to demyelinating diseases by increasing the expression and secretion of serine protease inhibitor clade A member 3N (SERPINA3N). This transition of homeostatic OLs to Serpina3n-expressing OLs (SerpinOLs) occurs not only in demyelinating disease, but also after stroke, endotoxin-induced injury, neurodegeneration, traumatic injury, and healthy aging. Mechanistically, direct injury to OLs, rather than inflammation alone, drives the transition. Phenotypically, SerpinOLs show inflammatory and immune-regulatory features and activation of signal transducer and activator of transcription 3 (STAT3), which is required for SERPINA3N induction. Functionally, SerpinOLs amplify neuroinflammation and glial activation toward pro-inflammatory and neurodegenerative states. Together, SerpinOLs represent a common population of injury-transduced OLs that contributes to CNS pathology beyond myelin production. This study identifies SerpinOLs, injury-responsive oligodendrocytes producing SERPINA3N, as a common cell state in disease and aging, which amplify neuroinflammation and glial activation beyond myelin-related functions in mice.

Abstract Recent DIII-D tokamak experiments have demonstrated the integration of intrinsic low-collisionality grassy edge-localized mode (ELM) regime with high-performance hybrid core scenario, possibly offering a core-edge compatible solution for ITER and future fusion reactors. This regime features grassy ELMs (with ELM energy loss over pedestal stored energy <2%) at ITER-relevant pedestal top collisionality (ν_e^*~0.1), ITER similar shape, while maintaining high core confinement (H_98y2~1.5) in non-inductive hybrid scenarios. A small ELM-focused database is constructed to investigate the parametric dependence of the small/grassy ELM regimes. Access and sustainment of this regime appear to be favored by high poloidal beta (β_p>1.5), higher ratio of separatrix-to-pedestal density (n_(e,sep)⁄n_(e,ped) >0.4) and low pedestal top collisionality (υ_(e,ped)^*=0.1-0.4). In this scenario, the pedestal width exceeds the prediction from EPED–KBM scaling, consistent with the expectation of a turbulence-limited pedestal. Linear modeling using ELITE indicates that this grassy ELM regime is along the peeling boundary. Relative to a large-ELM phase, the grassy-ELM phase exhibits a broader inner-target heat-flux width and a substantially reduced ELM-induced transient heat-flux increment. These results motivate further evaluation of low-collisionality grassy ELMs as a potentially reactor-relevant operating regime, while full-duration sustainment and compatibility with divertor detachment remain unresolved.

Linear and quasilinear magnetohydrodynamic (MHD) modeling is carried out for two DIII-D discharges that both featured a transition from quiescent H-mode (QH) to wide-pedestal QH (WPQH). The MHD perturbations, associated with the edge harmonic oscillations (EHOs) observed during the QH-phase in both discharges, are identified as low- n ( n is the toroidal mode number) resistive kink-peeling instabilities, with the ideal MHD counterpart remaining stable. The quasilinear model successfully simulates EHO-like perturbations during the QH phase in both discharges, confirming the experimental observations. A less intuitive finding is the EHO-like behavior involving the n = 2 perturbation, simulated for one of the discharges during the WPQH-phase. This result, while consistent with experimental observations, is obtained despite the fact that the initial perturbation is linearly stable. The eventual growth of the perturbation is solely due to nonlinear interaction between the MHD perturbation and the plasma toroidal flow. The occurrence of the EHO-like perturbation during the WPQH-phase is found to be sensitive to the initial profile of the plasma edge rotation. For DIII-D plasmas considered, the neoclassical toroidal viscosity, generated by three-dimensional low- n perturbations, is found to play a dominant role in modifying the edge flow during EHOs.

A window for quiescent H-mode (QH-mode) operation in DIII-D plasmas in the diagram of pedestal magnetohydrodynamic (MHD) stability was identified through linear MHD stability analysis, accounting for the effects of plasma rotation and ion diamagnetic drift. The operation window lies between the stability boundaries of the kink/peeling mode (K/PM) identified with and without the inclusion of plasma rotation effects. In this region, the mode remains unstable unless rotation effects are considered alongside the ion diamagnetic drift, which is consistently included in the analysis. The stabilization of the MHD mode, facilitated by the coupled effects of plasma rotation and ion diamagnetic drift, plays a crucial role in widening the window, enabling the attainment of the QH-mode state. Furthermore, the suppression of edge localized modes (ELM) can be achieved by controlling the pedestal structure to ensure the plasma state remains within the operation window. The location of the operation window in the stability diagram depends on the K/PM stability properties. Therefore, optimizing conditions for QH-mode requires adjustments based on changes in stability characteristics. A pressure pedestal and its associated bootstrap current density near the last closed flux surface are advantageous for situating the plasma state within the window. However, excessive current density can trigger ELMs. This trend was confirmed through comparisons of MHD stability diagrams between QH-mode and ELMy H-mode plasmas.

The low- n ( n is the toroidal mode number) magnetohydrodynamic (MHD) stability and plasma response are numerically investigated for various scenarios designed for STEP, that are relevant for the H-mode pedestal analysis. Control of the edge-localized modes (ELMs) with externally applied resonant magnetic perturbations (RMPs) is considered. Optimization of the ELM control coil current configuration, based on the computed plasma MHD response and well-established figures of merit validated on present-day experiments, finds reasonable robustness of a fixed coil phasing (for a given n -number) to control ELMs in all five STEP plasmas considered. Based on certain semi-empirical criteria, the required coil current to achieve ELM suppression is estimated to be about 10–20 kAt with the n = 1 or 2 RMP configuration and about 100–200 kAt for the n = 4 RMP. Systematic linear stability calculations are used to map out stability windows for the low- n kink-peeling modes, in terms of the ideal-wall location and variation of the edge safety factor q 95 with respect to the target design. The kink-peeling stability boundary is found to be generally sensitive to the q 95 variation, which has implications for achieving the quiescent H-mode regime in STEP. Full toroidal quasilinear initial-value simulations for these STEP plasmas find that generation of the edge-harmonic oscillations (EHOs) depends sensitively on the plasma scenario, the initial linear stability of the kink-peeling modes, the initial plasma toroidal flow and q 95 . In general, it is easier (more robust) to access the EHO-regime for two of the cases considered with smaller plasma volume and higher on-axis safety factor. Finally, quasilinear simulations find robust density pumpout due to applied RMPs in these STEP plasmas, but the effect on the plasma toroidal flow varies among different cases.

A central challenge in fusion energy is reconciling the high-confinement mode required for reactor performance with the intense intermittent relaxation events it produces, known as edge-localized modes. These instabilities arise in the steep pressure pedestal at the plasma edge when magnetohydrodynamic thresholds are crossed, inflicting damaging heat loads on reactor components. Here, we show that multiscale interactions between microscopic turbulence and macroscopic magnetohydrodynamic modes provide encouraging prospects for self-organized edge-localized modes regulation. Using direct quantitative measurements of multiscale modes, eddy dynamics, and turbulent flux, we show that small-scale electron drift wave turbulence actively scatters the large-scale peeling-ballooning modes. This scattering decorrelates the pressure and velocity fields of the instability, so arresting its growth. Our modeling and theoretical analysis confirm this suppression mechanism is effective even when conventional linear stability thresholds are exceeded. This work establishes a nonlinear principle for edge-localized modes stability, revealing how ambient micro-turbulence can be leveraged to maintain a macro-stable, high-performance pedestal for future fusion reactors.

PURPOSE. Glaucoma is the leading cause of irreversible blindness worldwide and encompasses a group of diseases characterized by optic nerve atrophy and visual field defects. Acute intraocular pressure (IOP) elevation is a key driver of retinal inflammation and optic nerve damage, often accompanied by microglial activation and dysregulated ferroptosis pathways. Vitamin K1, a fat-soluble vitamin, possesses anti-inflammatory and antioxidant properties, and has the potential to regulate ferroptosis. However, its mechanisms in alleviating retinal inflammation following acute IOP elevation remain unclear. METHODS. In vivo, we established a mouse model of acute ocular hypertension to evaluate the protective effects of vitamin K1 on the retina and visual function. Transcriptome sequencing was used to explore the underlying mechanisms by which vitamin K1 exerts its effects. Immunofluorescence and Western blot were used to assess retinal inflammation and observe ferroptosis in microglia. In vitro, we developed a BV2 cell OGDR model to investigate the regulatory effects of vitamin K1 on iron metabolism and inflammation in microglia. RESULTS. Our findings demonstrated that acute IOP elevation led to microglial activation, along with iron overload and ferroptosis in microglia. Further analyses revealed that microglial ferroptosis was accompanied by an upregulation of inflammatory cytokine gene expression and protein levels. Vitamin K1 intervention, however, inhibited microglial ferroptosis, alleviated retinal inflammation, minimized retinal ganglion cell (RGC) loss, and protected visual function. CONCLUSIONS. In conclusion, this study demonstrates that vitamin K1 exerts a protective effect by modulating microglial ferroptosis, thereby alleviating acute ocular hypertension-induced retinal inflammation.

The low-edge rotation, intrinsically ELM-free, and improved confinement wide-pedestal quiescent H-mode (QH-mode), discovered in DIII-D tokamak, has pedestal widths exceeding the EPED-kinetic-ballooning mode (KBM) model scaling typically by at least 25%. Ion-scale ( k(y)rho(s) < 1) microturbulence and its role in setting the pedestal structure is investigated using the radially local delta f gyrokinetic code CGYRO. The electromagnetic trapped electron mode (TEM) is unstable at the pedestal top, while plasma beta ( beta(e) ) is similar to 60% below the KBM onset threshold and the electron temperature gradient mode is found to be unstable in the peak gradient region. Nonlinear simulation reveals that the ion-scale turbulence could produce electron energy flux consistent with the flux inferred from power balance at the pedestal top, with a reasonable variation of the local E x B shearing rate; and the local neoclassical transport from NEO is dominant over the simulated turbulent transport in the ion energy flux channel. The simulated ion-scale turbulence produces much lower electron energy flux than inferred from experiment in the pedestal peak gradient region. A correction to the EPED-KBM pedestal width scaling is obtained based on the two-dimensional scan of pedestal top plasma beta ( beta(e) ) and normalized electron density and temperature scale lengths, a/Ln(e), a/LTe using CGYRO linear simulations. Mode transitions among TEM, micro-tearing mode, ion-temperature gradient mode and KBM, are observed in the 2D scan at the pedestal top. A fixed normalized growth rate for these drift-type modes is taken to determine the pedestal width scaling, which shows good consistency with the QH experimental database on pedestal heights and widths. The onset of KBM instabilities and the local E x B shear suppression criterion set the lower and upper limit for the pedestal width of standard QH-mode, wide-pedestal QH-mode and type-I ELMy H mode. A potentially higher and wider pedestal is expected from the new scaling of pedestal width. This work presents an improved understanding of the ion-scale micro-turbulence of wide-pedestal QH-mode and sheds light on a promising scenario for future reactors, including ITER and beyond.

AbstractIntroductionRepeated exposure to cocaine induces microglial activation. Cocaine exposure also induces a release of high mobility group box‐1 (HMGB1) from neurons into the extracellular space in the nucleus accumbens (NAc). HMGB1 is an important late inflammatory mediator of microglial activation. However, whether the secretion of HMGB1 acts on microglia or contributes to cocaine addiction is largely unknown.MethodsRats were trained by intraperitoneal cocaine administration and cocaine‐induced conditioned place preference (CPP). Expression of HMGB1 was regulated by viral vectors. Activation of microglia was inhibited by minocycline. Interaction of HMGB1 and the receptor for advanced glycation end products (RAGE) was disrupted by peptide.ResultsCocaine injection facilitated HMGB1 signaling, together with the delayed activation of microglia concurrently in the NAc. Furthermore, the inhibition of HMGB1 or microglia activation attenuated cocaine‐induced CPP. Box A, a specific antagonist to interrupt the interaction of HMGB1 and RAGE, abolished the expression of cocaine reward memory. Meanwhile, the inhibition of HMGB1–RAGE interaction suppressed cocaine‐induced microglial activation, as well as the consolidation of cocaine‐induced memory.ConclusionAll above results suggest that the neural HMGB1 induces activation of microglia through RAGE, which contributes to the consolidation of cocaine reward memory. These findings offer HMGB1–RAGE axis as a new target for the treatment of drug addiction.

BackgroundFew studies have examined patient preferences for telehealth in palliative care after the availability of COVID-19 vaccines. We examined patient preferences for video versus in-person visits and factors contributing to preferences in the post-vaccine era.MethodsThis is a cross-sectional survey of patients who were seen at our palliative care clinic between April 2021 and March 2022. Patients were surveyed directly their preference for either video or in-person visits for outpatient palliative care (primary outcome). We also surveyed preferences including convenience, cost, wait time, and perceptions of COVID-19 safety regarding their palliative virtual-video visit. We examined clinical factors associated with preferences with multivariate logistic regression.Results200 patients completed the survey. 132 (67%, 95% confidence interval [CI]: 60%, 74%) preferred virtual-video, while 16 (8%) preferred in-person visits during the COVID-19 pandemic. 120 (61%, 95% CI: 54%, 68%) preferred virtual-video after the pandemic. Patients perceived virtual-video favorably regarding travel and related costs (179 [91%]), convenience (175 [88%]), and wait time (136 [69%]). Multivariable analysis showed concerns for catching COVID-19 from healthcare providers (odds ratio [OR]: 4.20; 95% CI: 1.24–14.25; P=0.02) and feeling comfortable with computers or mobile devices (OR: 4.59; 95% CI: 1.02, 20.60; P=0.047) were significantly associated with preferring virtual-video. Patients who were of Hispanic or Latino ethnicity (OR: 0.25; 95% CI: 0.09, 0.71) and had increased dypsnea (OR: 0.74; 95% CI: 0.59, 0.93) were less likely to prefer video over in-person.ConclusionPatients expressed strong preference for video over in-person visits in the outpatient palliative care setting.

Viable magnetic fusion devices necessitate combining good confinement with effective power flux handling. A major concern for ITER, and devices beyond, is the divertor heat load width, which sets peak boundary heat loads on the plasma-facing materials. Current estimates of the heat flux width are narrow for future reactors. Here, we demonstrate how pedestal turbulence can expand into, or entrain, the stable scrape-off-layer and so broaden the heat flux width beyond these neoclassical predictions. Employing combined theoretical, computational, and experimental approaches, we focus on quiescent high confinement discharges on the DIII-D tokamak, but the results are of broader significance. Our findings uncover common trends in the edge turbulence intensity flux, the pressure perturbation skewness, and the turbulence mixing length, which together determine the heat flux width. This research demonstrates the physics of scrape-off-layer broadening by turbulence and highlights the promise of a turbulent pedestal for successful core-edge integration in ITER and future fusion devices.

Three-level Neutral-Point-Clamped (NPC) topology are extensively utilized in motor drive applications. However, two prevalent issues associated with Three-level NPC inverters are neutral-point (NP) fluctuations and common-mode voltage (CMV) suppression. To address these problems, an improved modulation strategy is proposed that effectively mitigates NP voltage imbalance and CMV. This strategy achieves CMV suppression by selecting vectors that produce smaller CMV for vector synthesis. For the NP voltage balance, it employs the selection of either a P/N type vectors while adjusting the action time of these vectors. Compared to traditional space vector pulse-width modulation (SVPWM) strategies, this approach simultaneously reduces NP voltage deviation and CMV. Furthermore, the expression for neutral-point current under this modulation strategy is derived, providing a practical method for the design of DC-side capacitors in three-level NPC inverters.

To address the needs for a fusion pilot plan design, DIII-D/EAST joint experiments on DIII-D have demonstrated high normalized beta β N ∼ 4.2, toroidal beta β T ∼ 3.3% with q min > 2, q 95 ⩽ 8 sustained for more than six energy confinement times in high poloidal beta regime. The excellent energy confinement quality ( H 98y2 ∼ 1.8) is achieved with an internal transport barrier at high line-averaged Greenwald density fraction f Gr > 0.9. The trapped gyro-Landau fluid (TGLF) modeling of the transport characteristics shows that the beam-driven rotation does not play an important role in the high confinement quality. The modeling also captures very well several transport features, giving us confidence in using integrated modeling to project these experimental results to future machines. The high-performance phase is terminated by fast-growing modes triggered near the n = 1 ideal-wall kink stability limit. New radio frequency (RF) capabilities for off-axis current drive could remove the residual ohmic current to achieve a fully non-inductive state, and improve the mode–wall coupling to increase the ideal-wall β N limit, enabling sustainment of the fully non-inductive high performance plasma in stationary conditions.

Background:Clear cell renal cell carcinoma (RCC) is the most common subtype of RCC. Although targeted therapy can provide superior treatment outcomes, it is prone to drug resistance, and individual responses to immunotherapy vary greatly. Therefore, finding new diagnostic and therapeutic targets for RCC is of considerable importance. Long noncoding RNA (lncRNA) GPRC5D-AS1 can serve as a biomarker in clinical applications and the prognosis of lung squamous cell carcinoma. However, the specific mechanism of action of lncRNA GPRC5D-AS1 in RCC has not yet been clarified. Therefore, this paper explores the expression of lncRNA GPRC5D-AS1 in the renal cancer cell line 786-0, and conducts a preliminary study of its molecular mechanism. Selecting nude mice for tumor experiments is because of the high genomic and physiological similarity between mice and humans. Conducting tumor research on mice allows for better control of experimental conditions, aiding researchers in more accurately observing and analysing tumor characteristics and responses. Methods:Small interfering RNA (siRNA) and plasmid cloning DNA (pcDNA) 3.1 were used to transfect renal cancer cell line 786-0 to silence and overexpress the lncRNA GPRC5D-AS1 gene. Quantitative real-time fluorescence polymerase chain reaction was used to detect the difference in lncRNA GPRC5D-AS1 expression in blank control group, negative control group, siGPRC5D-AS1 group and oeGPRC5D-AS1 group. The effects of silence and overexpression of lncRNA GPRC5D-AS11 on the proliferation of 786-0 cells were detected in cell colony formation experiments; the changes in the migration and invasion of 786-0 cells were detected via cell scratch assay and transwell assay, respectively; the differences in tumor growth between groups were determined via tumorigenesis experiments in nude mice; and the expression of proliferation-related protein [β-catenin, Ki67 and proliferating cell nuclear antigen (PCNA)] and invasion-related protein (N-cadherin and E-cadherin) were detected via Western blotting. Results:Compared with blank control group and negative control group, the siGPRC5D-AS1 group showed a significant decrease in the relative expression of lncRNA GPRC5D-AS1 (P<0.05), a significant increase in the number of proliferating cells and migrating cells (P<0.05), a significant increase in the tumor volume of nude mice (P<0.05), a significant increase in β-catenin, Ki67, PCNA and N-cadherin protein expression (P<0.05), and a significant decrease in E-cadherin protein expression (P<0.05); conversely, these results were opposite for the eGPRC5D-AS1 group. Conclusions:Silencing the expression of lncRNA GPRC5D-AS1 can enhance the proliferation, invasion, and migration ability of renal cancer cell line 786-0, which can be weakened by the overexpression of lncRNA GPRC5D-AS1.

Context. Corticosteroids are commonly prescribed in oncology, but few studies have examined its adverse events (AEs) compared to placebo control. Objectives. Using data from a double-blind, placebo-controlled randomized trial, we evaluated the association between the dose and duration of dexamethasone and serious AEs. Methods. This is a pre-planned secondary analysis of the Alleviating Breathlessness in Cancer Patients with Dexamethasone (ABCD) trial in which patients were randomized to dexamethasone 8 mg BID x1 week, then 4 mg BID x1 week or placebo, followed by an optional open-label phase with 4 mg BID x1 week, then 2 mg BID x1 week. The primary outcome was Grade 3+ AEs (CTCAE v4.03). We evaluated the association between AEs and dexamethasone exposure using multivariable logistic regression. Results. Among 119 cancer patients, 32 received intervention followed by open label (mean exposure 243 mg over 27 days), 47 received intervention with no open label, 20 received placebo followed by open label, and 20 received no dexamethasone. The most common AEs included insomnia (31%), dyspepsia (21%), neuropsychiatric symptoms (18%), and infections (17%). Overall, 38 (32%) had Grade 3+ AEs and 27 (23%) were hospitalized. Patients with the greatest exposure to dexamethasone experienced more Grade 3+ AEs compared to those with no exposure (65% vs. 15%); odds ratio of 15.1 (95% CI 1.4-160.8, Conclusion. Greater dexamethasone exposure, even at moderate doses, was associated with more serious AEs. Prescribers should cautiously weigh the risks and benefits of dexamethasone use, especially when considering for palliation of symptoms. J Pain Symptom Manage 2024;67:59-68. (c) 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Cognitive impairment is a multifactorial and multi-step pathological process that places a heavy burden on patients and the society. Neuroinflammation is one of the main factors leading to cognitive impairment. The inflammasomes are multi-protein complexes that respond to various microorganisms and endogenous danger signals, helping to initiate innate protective responses in inflammatory diseases. NLRP3 inflammasomes produce proinflammatory cytokines (interleukin IL-1β and IL-18) by activating caspase-1. In this review, we comprehensively describe the structure and functions of the NLRP3 inflammasome. We also explore the intrinsic relationship between the NLRP3 inflammasome and cognitive impairment, which involves immune cell activation, cell apoptosis, oxidative stress, mitochondrial autophagy, and neuroinflammation. Finally, we describe NLRP3 inflammasome antagonists as targeted therapies to improve cognitive impairment.

Pathological neovascularization is the hallmark of many vascular oculopathies. There is still a great deal of uncertainty surrounding retinal neovascularization research. A working hypothesis that astrocytic Yes-associated protein (YAP) act as a key factor in retinal neovascularization was proposed. And our study was conducted to verified this hypothesis. In vivo, we successfully generated mice deficient in YAP in astrocytes (YAPf/f GFAP-Cre mice) and set up oxygen-induced retinopathy (OIR) model. Pathological neovascularization was evaluated by immunofluorescence staining and western blotting. In vitro, cultured retinal astrocytes were transfected with YAP siRNA. Enzyme-linked immunosorbent assay (ELISA) and western blot were used to determine the proteins in the supernatants and cells. The results showed that YAP was upregulated and activated in the OIR mice retinas. Conditional ablation of YAP aggravated pathological neovascularization, along with the upregulation of vascular endothelial growth factor A (VEGF-A) and monocyte chemoattractant protein-1 (MCP-1). Studies in vitro confirmed that the knockdown of YAP in astrocytes lead to increases in VEGF-A and MCP-1 levels, thus enhancing pro-angiogenic capability of YAP-deficit astrocytes. In conclusion, astrocytic YAP alleviates retinal pathological angiogenesis by inhibiting the over-activation of astrocytes, which suppresses excessive VEGF-A production and neuroinflammation.

Chronic cerebral hypoperfusion (CCH) is a major global disease with chronic cerebral blood flow reduction. It is also the main cause of cognitive impairment and neurodegenerative diseases. Pyroptosis, a novel form of cell death, is characterized by the rupture of the cell membrane and the release of pro-inflammatory mediators. In recent years, an increasing number of studies have identified the involvement of pyroptosis and its mediated inflammatory response in the pathological process of CCH. Therefore, preventing the activation of pyroptosis following CCH is beneficial to inhibit the inflammatory cascade and reduce brain injury. In this review, we discuss the research progress on the relationship between pyroptosis and CCH, in order to provide a reference for research in related fields.

BackgroundHypertension, sleep disorders, and depression are highly prevalent in the elderly population and are all associated with cognitive impairment, but the role that sleep quality and depression play in the association between hypertension and cognitive impairment is unclear. The aim of this study was to investigate whether sleep quality and depression have a mediating role in the association between hypertension and cognitive impairment.MethodsA cross-sectional study was conducted to collect data from the Tongji Hospital Comprehensive Geriatric Assessment Database. Sleep quality, depression and cognitive function were measured by the Pittsburgh Sleep Quality Index (PSQI), the Geriatric Depression Scale (GDS-15) and the Mini-Mental State Examination (MMSE), respectively. Correlation analysis, regression analysis and Bootstrap analysis were used to examine correlations between key variables and mediating effects of sleep quality and depression. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing.ResultsA total of 827 participants were included, hypertension was present in 68.3% of the sample. After correcting for covariates, hypertensive patients aged 65 years or older had worse cognitive function, poorer-sleep quality and higher levels of depression. Sleep quality was significantly negatively associated with depression and cognitive function, while depression was negatively associated with cognitive function. Mediation analysis revealed that hypertension can affect cognitive function in older adults through a single mediating effect of sleep quality and depression and a chain mediating effect of sleep quality and depression.ConclusionThis study found that sleep quality and depression can mediate the relationship between hypertension and cognitive function in elderly. Enhanced supervision of sleep quality and depression in elderly patients with hypertension may be beneficial in maintaining cognitive function.

Context. The COVID-19 pandemic represents a source of distress in patients with advanced cancer; however, few studies have examined the extent of pandemic-related distress in the postvaccine era.Objectives. We conducted a cross-sectional survey to examine pandemic-related distress among patients seen by palliative care after vaccine availability.Methods. Patients at our palliative care clinic were surveyed from April 2021 to March 2022 regarding 1) pandemic-related distress level, 2) potential contributors to pandemic-related distress, 3) coping strategies, 4) demographic factors and symptom burden. Univariate and multivariate analyses identified factors associated with pandemic-related distress.Results. A total of 200 patients completed the survey. Of 79 (40%, 95% confidence interval [CI]: 33%, 46%) reported worse pandemic-related distress. Patients who reported greater distress were more likely to report worse social isolation (67 [86%] vs. 52 [43%]), staying home more often (75 [95%] vs. 95 [79%]), more negative experience staying at home (26 [33%] vs. 11 [9%]), worse stress with child-care duties (14 [19%] vs. 4 [3%]), less seeing family/friends (63 [81%] vs. 72 [60%]), and more difficulty traveling to medical appointments (27 [35%] vs. 20 [17%]). Thirty-seven patients (19%) reported more difficulty getting medical appointments. In multivariable analysis, younger age (odds ratio [OR], 0.97; 95% CI, 0.92-0.99; P = 0.01), worse isolation status (OR, 6.87; 95% CI, 2.76-17.12; P< 0.001), and more negative attitude towards staying home (OR, 4.49; 95% CI, 1.6-12.57; P = 0.004) were associated with pandemic-related distress.Conclusions. Patients with advanced cancer continued to experience pandemic-related distress in the postvaccine era. Our findings highlight potential opportunities to support patients. J Pain Symptom Manage 2023;66:328-337. (c) 2023 Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine.