Association Between Changes in Smoking Habits and Incident Fracture After Acute Ischemic Stroke.

BACKGROUND: Survivors of stroke, particularly the older population, are at an increased risk of falls and incident fractures. Smoking is a widely recognized risk factor for fractures. However, the association between changes in smoking habits before and after an index stroke and increased risk of fracture remains unelucidated. METHODS AND RESULTS: Using the Korean National Health Insurance program, patients with ischemic stroke between 2010 and 2016 were enrolled. Individuals were classified by smoking habits: "never smoker," "former smoker," "smoking quitter," "new smoker," and "sustained smoker." The primary outcome was the composite outcome of the vertebral, hip, and any fractures. Multivariable Cox proportional hazards regression analysis was conducted, using the never-smoker group as the reference. Among 177 787 patients with health screening data within 2 years before and after ischemic stroke, 14 991 (8.43%) patients had any fractures. After multivariable adjustment, the sustained smokers had a significantly increased risk of composite primary outcomes of any, vertebral, and hip fractures (adjusted HR [aHR], 1.222 [95% CI, 1.124-1.329]; aHR, 1.27 [95% CI, 1.13-1.428]; aHR, 1.502 [95% CI, 1.218-1.853], respectively). Additionally, the new smoker group exhibited a similar or higher risk of any fractures and hip fractures (aHR, 1.218 [95% CI, 1.062-1.397]; aHR, 1.772 [95% CI, 1.291-2.431], respectively). CONCLUSIONS: Sustained smokers had a significantly increased risk of vertebral and hip fractures after an ischemic stroke. The risk of any hip fractures was higher in new smokers after ischemic stroke. As poststroke fractures are detrimental to the rehabilitation process of patients with stroke, physicians should actively advise patients to stop smoking.

Fostering Charge Carrier Transport and Absorber Growth Properties in CZTSSe Thin Films with an ALD-SnO2 Capping Layer.

The present study demonstrates that precursor passivation is an effective approach for improving the crystallization process and controlling the detrimental defect density in high-efficiency Cu2ZnSn(S,Se)4 (CZTSSe) thin films. It is achieved by applying the atomic layer deposition (ALD) of the tin oxide (ALD-SnO2) capping layer onto the precursor (Cu-Zn-Sn) thin films. The ALD-SnO2 capping layer was observed to facilitate the homogeneous growth of crystalline grains and mitigate defects prior to sulfo-selenization in CZTSSe thin films. Particularly, the CuZn and SnZn defects and deep defects associated with Sn were effectively mitigated due to the reduction of Sn2+ and the increase in Sn4+ levels in the kesterite CZTSSe film after introducing ALD-SnO2 on the precursor films. Subsequently, devices integrating the ALD-SnO2 layer exhibited significantly reduced recombination and efficient charge transport at the heterojunction interface and within the bulk CZTSSe absorber bulk properties. Finally, the CZTSSe device showed improved power conversion efficiency (PCE) from 8.46% to 10.1%. The incorporation of ALD-SnO2 revealed reduced defect sites, grain boundaries, and surface roughness, improving the performance. This study offers a systematic examination of the correlation between the incorporation of the ALD-SnO2 layer and the improved PCE of CZTSSe thin film solar cells (TFSCs), in addition to innovative approaches for improving absorber quality and defect control to advance the performance of kesterite CZTSSe devices.

Increased incidence and diverse manifestations of multiple evanescent white dot syndrome during the COVID-19 pandemic.

The advent of coronavirus disease 2019 (COVID-19) pandemic has affected the incidence and course of various diseases and numerous studies have investigated ocular involvement associated with COVID-19 and corresponding vaccines. In this study, we compared the incidence of multiple evanescent white dot syndrome (MEWDS) before and during the COVID-19 pandemic at a single center in Korea and analyzed the demographic and clinical features of patients with MEWDS presenting during the COVID-19 pandemic. We categorized patients with MEWDS into two groups according to date of diagnosis. Pre-COVID19 group included patients diagnosed during the pre-pandemic period (between March 11, 2017, and March 10, 2020), whereas post-COVID19 group included patients diagnosed during the pandemic period (between March 11, 2020, and March 10, 2023). 6 and 12 patients were included in pre-COVID19 group and post-COVID19 group, respectively. Among all hospital visits during the pre-pandemic and pandemic periods, 0.011% and 0.030% were due to MEWDS, indicating a significant increase during the pandemic (p = 0.029, B = 2.756). The annual incidence of patients with MEWDS in 2017-2022 were 0.73, 0.75, 0.78, 1.32, 2.49, and 2.07 per 10,000 population, respectively, corresponding to a significant increase (p = 0.039, B = 1.316). Our results imply that the incidence and manifestation of MEWDS are likely to become more diverse in the COVID-19 pandemic era.

Association between physical activity changes and incident myocardial infarction after ischemic stroke: a nationwide population-based study.

BACKGROUND: The impact of changes in physical activity after ischemic stroke (IS) on the subsequent myocardial infarction (MI) risk is not fully understood. We aimed to investigate the effects of changes in physical activity on the risk of MI after acute IS using data from the Korean National Health Insurance Services Database. METHODS: 224,764 patients newly diagnosed with IS between 2010 and 2016 who underwent two serial biannual health checkups were included. The participants were divided into four categories according to changes in their physical activity: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was a new diagnosis of incident MI. Multivariable Cox proportional models were used to assess the effects of changes in exercise habits on the risk of MI. RESULTS: After a median of 4.25 years of follow-up, 6,611 (2.94%) MI cases were observed. After adjusting for confounders, new exercisers and exercise maintainers were significantly associated with a lower risk of incident MI than persistent non-exercisers (aHR, 0.849; 95% CI, 0.792-0.911; P-value < 0.001; and aHR, 0.746; 95% CI, 0.696-0.801; P-value < 0.001, respectively). Effects were consistent across sexes, more pronounced in those > 65 years. Notably, any level of physical activity after stroke was associated with a reduced MI risk compared to no exercise. CONCLUSIONS: In this nationwide cohort study, commencing or sustaining physical activity after an IS corresponded to a diminished likelihood of subsequent MI development. Advocating physical activity in ambulatory stroke survivors could potentially attenuate the prospective risk of MI.

Optimal use of antithrombotic agents in recent small subcortical strokes accompanied by atrial fibrillation.

BACKGROUND: This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF). METHODS: We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis. RESULTS: Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis. CONCLUSION: AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone.

A multimodal machine learning model for predicting dementia conversion in Alzheimer's disease.

Alzheimer's disease (AD) accounts for 60-70% of the population with dementia. Mild cognitive impairment (MCI) is a diagnostic entity defined as an intermediate stage between subjective cognitive decline and dementia, and about 10-15% of people annually convert to AD. We aimed to investigate the most robust model and modality combination by combining multi-modality image features based on demographic characteristics in six machine learning models. A total of 196 subjects were enrolled from four hospitals and the Alzheimer's Disease Neuroimaging Initiative dataset. During the four-year follow-up period, 47 (24%) patients progressed from MCI to AD. Volumes of the regions of interest, white matter hyperintensity, and regional Standardized Uptake Value Ratio (SUVR) were analyzed using T1, T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores (HOC) and Fazekas scales. As a result of testing the robustness of the model, the GBM model was the most stable, and in modality combination, model performance was further improved in the absence of T2-FLAIR image features. Our study predicts the probability of AD conversion in MCI patients, which is expected to be useful information for clinician's early diagnosis and treatment plan design.

Peripapillary microvasculature and retinal nerve fiber layer damage according to the severity of diabetic retinopathy.

PURPOSE: To identify damage to the inner retinal layer and microvasculature in the peripapillary area according to the severity of diabetic retinopathy (DR). METHODS: Patients were divided into four groups: control (group 1), type 2 diabetes (T2DM) without DR (group 2), mild to moderate nonproliferative DR (NPDR) (group 3), and severe NPDR (group 4). The peripapillary retinal nerve fiber layer (pRNFL) thickness and peripapillary vessel density (VD) were compared. Linear regression analysis was performed to identify factors associated with the DR severity. RESULTS: The average pRNFL thicknesses were 96.2 ± 7.1, 94.1 ± 9.6, 92.0 ± 9.9, and 90.3 ± 12.4 µm in groups 1, 2, 3, and 4, respectively (P = 0.003) (post hoc analyses: group 1 vs. group 2, P = 0.529; group 2 vs. group 3, P = 0.627; group 2 vs. group 4, P = 0.172; group 3 vs. group 4, P = 0.823). The VDs of the outer ring were 18.9 ± 0.6, 18.4 ± 0.8, 17.9 ± 1.1, and 17.3 ± 1.6 mm-1 in groups 1, 2, 3 and 4, respectively (P < 0.001) (all pairwise comparisons, P < 0.050). In multivariate analysis, the VD of the outer ring (B = - 0.35, P < 0.001) was significantly associated with the DR severity. CONCLUSIONS: The peripapillary microvasculature reflects retinal damage following DR progression better than the structure of the pRNFL.

Strategic white matter hyperintensity locations associated with post-stroke cognitive impairment: A multicenter study in 1568 stroke patients.

BACKGROUND: Post-stroke cognitive impairment (PSCI) occurs in up to 50% of stroke survivors. Presence of pre-existing vascular brain injury, in particular the extent of white matter hyperintensities (WMH), is associated with worse cognitive outcome after stroke, but the role of WMH location in this association is unclear. AIMS: We determined if WMH in strategic white matter tracts explain cognitive performance after stroke. METHODS: Individual patient data from nine ischemic stroke cohorts with magnetic resonance imaging (MRI) were harmonized through the Meta VCI Map consortium. The association between WMH volumes in strategic tracts and domain-specific cognitive functioning (attention and executive functioning, information processing speed, language and verbal memory) was assessed using linear mixed models and lasso regression. We used a hypothesis-driven design, primarily addressing four white matter tracts known to be strategic in memory clinic patients: the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus. RESULTS: The total study sample consisted of 1568 patients (39.9% female, mean age = 67.3 years). Total WMH volume was strongly related to cognitive performance on all four cognitive domains. WMH volume in the left anterior thalamic radiation was significantly associated with cognitive performance on attention and executive functioning and information processing speed and WMH volume in the forceps major with information processing speed. The multivariable lasso regression showed that these associations were independent of age, sex, education, and total infarct volume and had larger coefficients than total WMH volume. CONCLUSION: These results show tract-specific relations between WMH volume and cognitive performance after ischemic stroke, independent of total WMH volume. This implies that the concept of strategic lesions in PSCI extends beyond acute infarcts and also involves pre-existing WMH. DATA ACCESS STATEMENT: The Meta VCI Map consortium is dedicated to data sharing, following our guidelines.

Solution-processable low-voltage carbon nanotube field-effect transistors with high-krelaxor ferroelectric polymer gate insulator.

Achieving energy-efficient and high-performance field-effect transistors (FETs) is one of the most important goals for future electronic devices. This paper reports semiconducting single-walled carbon nanotube FETs (s-SWNT-FETs) with an optimized high-krelaxor ferroelectric insulator P(VDF-TrFE-CFE) thickness for low-voltage operation. The s-SWNT-FETs with an optimized thickness (∼800 nm) of the high-kinsulator exhibited the highest average mobility of 14.4 cm2V-1s-1at the drain voltage (ID) of 1 V, with a high current on/off ratio (Ion/off>105). The optimized device performance resulted from the suppressed gate leakage current (IG) and a sufficiently large capacitance (>50 nF cm-2) of the insulating layer. Despite the extremely high capacitance (>100 nF cm-2) of the insulating layer, an insufficient thickness (<450 nm) induces a highIG, leading to reducedIDand mobility of s-SWNT-FETs. Conversely, an overly thick insulator (>1200 nm) cannot introduce sufficient capacitance, resulting in limited device performance. The large capacitance and sufficient breakdown voltage of the insulating layer with an appropriate thickness significantly improved p-type performance. However, a reduced n-type performance was observed owing to the increased electron trap density caused by fluorine proportional to the insulator thickness. Hence, precise control of the insulator thickness is crucial for achieving low-voltage operation with enhanced s-SWNT-FET performance.

Effects of Prior Metformin Use on Stroke Outcomes in Diabetes Patients with Acute Ischemic Stroke Receiving Endovascular Treatment.

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET- groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12-0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14-0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0-2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting.

CMOS-Integrated Ternary Content Addressable Memory using Nanocavity CBRAMs for High Sensing Margin.

The development of data-intensive computing methods imposes a significant load on the hardware, requiring progress toward a memory-centric paradigm. Within this context, ternary content-addressable memory (TCAM) can become an essential platform for high-speed in-memory matching applications of large data vectors. Compared to traditional static random-access memory (SRAM) designs, TCAM technology using non-volatile resistive memories (RRAMs) in two-transistor-two-resistor (2T2R) configurations presents a cost-efficient alternative. However, the limited sensing margin between the match and mismatch states in RRAM structures hinders the potential of using memory-based TCAMs for large-scale architectures. Therefore, this study proposes a practical device engineering method to improve the switching response of conductive-bridge memories (CBRAMs) integrated with existing complementary metal-oxide-semiconductor (CMOS) transistor technology. Importantly, this work demonstrates a significant improvement in memory window reaching 1.87 × 107 by incorporating nanocavity arrays and modifying electrode geometry. Consequently, TCAM cells using nanocavity-enhanced CBRAM devices can exhibit a considerable increase in resistance ratio up to 6.17 × 105, thereby closely approximating the sensing metrics observed in SRAM-based TCAMs. The improved sensing capability facilitates the parallel querying of extensive data sets. TCAM array simulations using experimentally verified device models indicate a substantial sensing margin of 65× enabling a parallel search of 2048 bits.

Experimental analysis and prediction of radionuclide solubility using machine learning models: Effects of organic complexing agents.

Radioactive wastes contain organic complexing agents that can form complexes with radionuclides and enhance the solubility of these radionuclides, increasing the mobility of radionuclides over great distances from a radioactive waste repository. In this study, four radionuclides (cobalt, strontium, iodine, and uranium) and three organic complexing agents (ethylenediaminetetraacetic acid, nitrilotriacetic acid, and iso-saccharic acid) were selected, and the solubility of these radionuclides was assessed under realistic environmental conditions such as different pHs (7, 9, 11, and 13), temperatures (10 °C, 20 °C, and 40 °C), and organic complexing agent concentrations (10-5-10-2 M). A total of 720 datasets were generated from solubility batch experiments. Four supervised machine learning models such as the Gaussian process regression (GPR), ensemble-boosted trees, artificial neural networks, and support vector machine were developed for predicting the radionuclide solubility. Each ML model was optimized using Bayesian optimization algorithm. The GPR evolved as a robust model that provided accurate predictions within the underlying solubility patterns by capturing the intricate relationships of the independent parameters of the dataset. At an uncertainty level of 95%, both the experimental results and GPR simulated estimations were closely correlated, confirming the suitability of the GPR model for future explorations.

Enhanced N-type Semiconducting Performance of Asymmetric Monochlorinated Isoindigo-based Semiregioregular Polymers under Dynamic Forces.

The asymmetric monochlorination strategy not only effectively addresses the steric issues in conventional dichlorination but also enables the development of promising acceptor units and semiregioregular polymers. Herein, monochlorinated isoindigo (1CIID) is successfully designed and synthesized by selectively introducing single chlorine (Cl) atoms. Furthermore, the 1CIID copolymerizes with two donor counterparts, centrosymmetric 2,2'-bithiophene (2T) and axisymmetric 4,7-di(thiophen-2-yl)benzo[1,2,5]thiadiazole (DTBT), forming two polymers, P1CIID-2T and P1CIID-DTBT. These polymers exhibit notable differences in backbone linearity and dipole moments, influenced by the symmetry of their donor counterparts. In particular, P1CIID-2T, which contains a centrosymmetric 2T unit, demonstrates a linear backbone and a significant dipole moment of 10.20 D. These properties contribute to the favorable film morphology of P1CIID-2T, characterized by highly ordered crystallinity in the presence of fifth-order (500) X-ray diffraction peaks. Notably, P1CIID-2T exhibits a significant improvement in molecular alignment under dynamic force, resulting in over 8-fold improvement in the performance of organic field-effect transistor (OFET) devices, with superior electron mobility up to 1.22 cm2 V-1 s-1. This study represents the first synthesis of asymmetric monochlorinated isoindigo-based conjugated polymers, highlighting the potential of asymmetric monochlorination for developing n-type semiconducting polymers. Moreover, our findings provide valuable insights into the relationship between the molecular structure and properties.

Secular Trends in Outcomes and Impact of Novel Oral Anticoagulants in Atrial Fibrillation-Related Acute Ischemic Stroke.

BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.

Evaluation of a Photo Captioning Cognitive Empathy Intervention for Dementia Caregivers.

OBJECTIVES: The goal of this study was to develop and evaluate an intervention aimed at increasing cognitive empathy, improving mental health, and reducing inflammation in dementia caregivers, and to examine the relevant neural and psychological mechanisms. METHODS: Twenty dementia caregivers completed an intervention that involved taking 3-5 daily photographs of their person living with dementia (PLWD) over a period of 10 days and captioning those photos with descriptive text capturing the inner voice of the PLWD. Both before and after the intervention, participants completed questionnaires, provided a blood sample for measures of inflammation, and completed a neuroimaging session to measure their neural response to viewing photographs of their PLWD and others. RESULTS: 87% of enrolled caregivers completed the intervention. Caregivers experienced pre- to post-intervention increases in cognitive empathy (i.e. Perspective-Taking) and decreases in both burden and anxiety. These changes were paralleled by an increased neural response to photographs of their PLWD within brain regions implicated in cognitive empathy. CONCLUSION: These findings warrant a larger replication study that includes a control condition and follows participants to establish the duration of the intervention effects. CLINICAL IMPLICATIONS: Cognitive empathy interventions may improve caregiver mental health and are worthy of further investigation.

Features of optical coherence tomography angiography in age-related macular degeneration with residual fluid after three loading doses of aflibercept.

BACKGROUND: To identify the macular neovascularization (MNV) features in exudative age-related macular degeneration (AMD) patients who exhibited residual fluid after receiving three loading doses of aflibercept. METHODS: Patients were classified into two groups: Group 1, which did not exhibit intraretinal fluid (IRF) and subretinal fluid (SRF), and Group 2, which did exhibit IRF and/or SRF. Optical coherence tomography angiography (OCTA) features were assessed and compared between the groups. RESULTS: A total of 101 eyes were enrolled; 65 for Group 1 and 36 for Group 2. No significant differences were found in baseline MNV size (2.94 ± 2.51 µm2 vs. 2.22 ± 2.26 µm2, P = 0.178) or vessel density (47.1 ± 15.4 % vs. 41.3 ± 10.5%, P = 0.052) between Groups 1 and 2. There were significant differences in the presence of loops (52.3% vs. 75%, P = 0.026) and peripheral arcades (29.2% vs. 55.6%, P < 0.001) at baseline between the two groups. In Group 1, there was a significant reduction in the presence of branching (P < 0.001) and loops (P = 0.016) after treatment. In Group 2, only the presence of branching decreased significantly (P < 0.001) after treatment. Multivariable analysis revealed that the presence of a peripheral arcade (B = 4.77, P = 0.001) was significantly associated with residual fluid. CONCLUSIONS: Although responding to treatment, the presence of loops and peripheral arcades in exudative AMD patients may contribute to residual fluid following the three loading doses of aflibercept. The peripheral arcade, in particular, may play a more significant role in the presence of residual fluid.

Retinal neurodegeneration in diabetic retinopathy with systemic hypertension.

PURPOSE: To identify the impact of hypertension (HTN) on inner retinal layer thickness in patients with diabetic retinopathy (DR). METHODS: In this retrospective cross-sectional study, participants were divided into three groups: type 2 diabetes patients without DR (DM group), patients with DR (DR group), and patients with both DR and HTN (DR+HTN group). The peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses, measured using optical coherence tomography, were compared among the groups. RESULTS: A total of 470 eyes were enrolled: 224 eyes in the DM group, 131 eyes in the DR group, and 115 eyes in the DR+HTN group. The mean RNFL thicknesses were 95.0 ± 7.7, 92.5 ± 10.1, and 89.2 ± 11.2 µm, and the mean GC-IPL thicknesses were 84.0 ± 5.7, 82.0 ± 7.6, and 79.2 ± 8.1 µm in each group, respectively (all P < 0.001). In the DR+HTN group, the DR stage showed a significant association with pRNFL (B = - 5.38, P = 0.014) and GC-IPL (B = - 5.18, P = 0.001) thicknesses in multivariate analyses. Subgroup analyses revealed that pRNFL (P = 0.007) and GC-IPL (P = 0.005) thicknesses decreased significantly as DR progressed only in the DR+HTN group. CONCLUSIONS: Patients with both DR and HTN exhibited much thinner pRNFL and GC-IPL, compared with patients with DR only. These results may have been related to the amplified diabetic retinal neurodegeneration and synergistic impact of ischemia in DR patients with concurrent HTN. Additionally, the progression of DR resulted in more severe inner retinal damage when combined with HTN.

Network analysis of neuropsychiatric, cognitive, and functional complications of stroke: implications for novel treatment targets.

AIM: Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aimed to identify interactions of poststroke complications using network analysis in diverse stroke samples. METHODS: Data from 2185 patients were sourced from member studies of STROKOG (Stroke and Cognition Consortium), an international collaboration of stroke studies. Networks were generated for each cohort, whereby nodes represented neuropsychiatric symptoms, cognitive deficits, and disabilities on activities of daily living. Edges characterized associations between them. Centrality measures were used to identify hub items. RESULTS: Across cohorts, a single network of interrelated poststroke complications emerged. Networks exhibited dissociable depression, apathy, fatigue, cognitive impairment, and functional disability modules. Worry was the most central symptom across cohorts, irrespective of the depression scale used. Items relating to activities of daily living were also highly central nodes. Follow-up analysis in two studies revealed that individuals who worried had more densely connected networks than those free of worry (CASPER [Cognition and Affect after Stroke: Prospective Evaluation of Risks] study: S = 9.72, P = 0.038; SSS [Sydney Stroke Study]: S = 13.56, P = 0.069). CONCLUSION: Neuropsychiatric symptoms are highly interconnected with cognitive deficits and functional disabilities resulting from stroke. Given their central position and high level of connectedness, worry and activities of daily living have the potential to drive multimorbidity and mutual reinforcement between domains of poststroke complications. Targeting these factors early after stroke may have benefits that extend to other complications, leading to better stroke outcomes.

The MYST Family Histone Acetyltransferase SasC Governs Diverse Biological Processes in Aspergillus fumigatus.

The conserved MYST proteins form the largest family of histone acetyltransferases (HATs) that acetylate lysines within the N-terminal tails of histone, enabling active gene transcription. Here, we have investigated the biological and regulatory functions of the MYST family HAT SasC in the opportunistic human pathogenic fungus Aspergillus fumigatus using a series of genetic, biochemical, pathogenic, and transcriptomic analyses. The deletion (Δ) of sasC results in a drastically reduced colony growth, asexual development, spore germination, response to stresses, and the fungal virulence. Genome-wide expression analyses have revealed that the ΔsasC mutant showed 2402 significant differentially expressed genes: 1147 upregulated and 1255 downregulated. The representative upregulated gene resulting from ΔsasC is hacA, predicted to encode a bZIP transcription factor, whereas the UV-endonuclease UVE-1 was significantly downregulated by ΔsasC. Furthermore, our Western blot analyses suggest that SasC likely catalyzes the acetylation of H3K9, K3K14, and H3K29 in A. fumigatus. In conclusion, SasC is associated with diverse biological processes and can be a potential target for controlling pathogenic fungi.

Changes in peripapillary microvasculature in patients with type 2 diabetes patients: effect of systemic hypertension.

To determine the effect of hypertension (HTN) on the peripapillary microvasculature in type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR). The patients were classified into three groups: the control group (group 1), T2DM group (group 2), and both T2DM and HTN group (group 3). Peripapillary vessel density (VD) was compared using analysis of covariance and linear regression analysis was performed to identify the factors affecting the peripapillary VD. A total of 286 eyes were enrolled: 124 in group 1, 111 in group 2, and 51 in group 3. The peripapillary VDs for the full area were 18.3 ± 0.6, 17.8 ± 1.0, and 17.3 ± 1.2 mm-1 in group 1, group 2, and group 3, respectively, which were significantly different after adjustment for age and best-corrected visual acuity (P < 0.001). In post hoc analyses, group 1 versus group 2 (P < 0.001), group 1 versus group 3 (P < 0.001), and group 2 versus group 3 (P = 0.001) showed significant differences. In linear regression analysis, HTN (B = - 0.352, P = 0.043) and peripapillary retinal nerve fiber layer (pRNFL) thickness (B = 0.045, P < 0.001) were significantly associated with peripapillary VD in T2DM patients. Peripapillary VD in T2DM patients without clinical DR were lower compared to normal controls, and they were more decreased when HTN was comorbid. The combination of ischemic damage by high blood pressure and impairment of the neurovascular unit by hyperglycemia would result in more severe deterioration of peripapillary microvasculature, and this impairment could be also reflected by pRNFL thinning.