Reasonable Request Research Articles

Investigating undiagnosed Fabry disease in young adults with ischemic stroke: A multicenter cohort study.

The global prevalence of ischemic stroke in young adults is increasing, leading to a significant social impact. Fabry disease is a recognized cause of ischemic stroke in young patients, and although disease-modifying treatments are available, further evidence is needed to confirm their effectiveness in reducing the incidence of ischemic strokes. This study aimed to identify undiagnosed Fabry disease in young adult patients with ischemic stroke in a Taiwanese cohort. This multicenter, prospective cohort study enrolled patients aged 20-55 years who had experienced an ischemic stroke or transient ischemic attack (TIA) within 10 days, from 1 January 2016 to 31 December 2020. Screening for Fabry disease was performed using a dry blood test to measure α-galactosidase activity in male patients and blood globotriaosylsphingosine (lyso-Gb3) levels in female patients. For patients with positive screen results, genetic diagnosis of Fabry disease was pursued through Sanger sequencing of the GLA gene, covering all exons and a segment of intron 4. A total of 977 patients (659 male, 68%) were enrolled from seven hospitals across Taiwan. Four patients (0.4%, all male) had positive screening results, and two patients (0.2%) were genetically diagnosed with Fabry disease. Case 1 had the GLA c.658C>T mutation and experienced ischemic stroke in the bilateral occipital regions. Case 2 had the GLA c.640-801G>A mutation and experienced an ischemic stroke in the left superficial watershed area. The prevalence of undiagnosed Fabry disease in this cohort of Taiwanese young adults with ischemic stroke or TIA was 0.3% among the young male population. Understanding the prevalence of undiagnosed Fabry disease in young adults with ischemic stroke could help shape future Fabry disease screening policies. The collected data will be available upon reasonable request from the corresponding author.

Efficiency and Simulation of Thailand's Chiang Mai University Model for COVID-19 Mass Vaccination Hub (CMU-MVH Model).

Mass vaccination is crucial for achieving herd immunity and controlling pandemics. Simulation models predict vaccination outcomes. This study evaluates efficiency and designs a tailored vaccination plan for Thailand. Data was derived from a COVID-19 Mass Vaccination Hub (MVH) in Chiang Mai, Thailand. It was taken between June 2021 and December 2021. The discreet event simulation model is developed in Arena Simulation Enterprise Suite version 14.0. The operational efficiency of Chiang Mai University Mass Vaccination Hub (CMU-MVH) was 1,073 vaccinations per 8 hours with 38 service staff. The average processing times (APT) were 2.5 minutes for the registration station, 12.2 minutes for the assessment station, 8.3 minutes for vaccination, and 28.2 minutes for observation. With 100% staff availability and staff utilization ranging from 0.5 to 0.7, the CMU-MVH could handle 180 to 230 vaccinees per hour or 1,227 to 1,527 vaccinees per day. Reduced staff availability leads to an increase in average processing time, especially when staff availability is lower or equal to 60%. The CMU-MVH could handle approximately a thousand vaccinations within 8 working hours. This capability could assist policymakers in developing more effective strategies and planning for future mass vaccinations. The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Clinical characteristics, in-hospital management, and outcomes among patients hospitalized for acute ischemic stroke in rural versus urban hospitals in China: A nationwide hospital-based study.

Efforts to improve rural stroke care have intensified in China. However, high-quality comprehensive data on the differences in care and outcomes between rural and urban hospitals are limited. We analyzed data on patients with acute ischemic stroke hospitalized in the China Stroke Center Alliance hospitals from 2015 to 2022. The in-hospital management measures assessed included nine acute and five discharge management measures. Outcomes evaluated included death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACE), disability at discharge, and in-hospital complications. We enrolled 1,583,271 patients with acute ischemic stroke from 1930 hospitals, comprising 1086 (56.3%) rural sites with 735,452 patients and 844 (43.7%) urban sites with 847,891 patients. Patients in rural hospitals demonstrate suboptimal management measures compared to those in urban hospitals, including lower rates of intravenous recombinant tissue plasminogen activator within 4.5 h (26.0% vs 28.3%; difference: -2.3% (-2.5% to -2.0%)), endovascular treatment (0.6% vs 1.9%; difference: -1.3% (-1.3% to -1.2%)), vessel assessment (88.5% vs 92.0%; difference: -3.5% (95% confidence interval (CI): -3.6% to -3.4%)), and anticoagulants for atrial fibrillation at discharge (42.9% vs 47.7%; difference: -4.8% (95% CI: -5.4% to -4.2%)). Overall, the rural-urban disparity in in-hospital outcomes was small. Rural patients had a slightly higher rate of in-hospital death/DAMA (9.0% vs 8.0%; adjusted odds ratio (OR): 1.22 (95% CI: 1.20-1.23); adjusted risk difference (aRD): 1.3% (95% CI: 1.2%-1.4%)) and a slightly lower rate of complications (10.9% vs 13.0%; aOR: 0.83 (95% CI: 0.82-0.84); aRD: -1.3% (95% CI: -1.3% to -1.3%)). No notable rural-urban differences were observed in MACE and disability at discharge. Patients in rural hospitals demonstrated suboptimal management measures and had higher rates of in-hospital death/DAMA compared to those in urban hospitals. Prioritizing the allocation of health resources to rural hospitals is essential to improve healthcare quality and outcomes. The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Home and workforce reintegration one year after thrombectomy in acute stroke patients.

Endovascular thrombectomy (EVT) combined with intravenous thrombolysis is the current standard treatment for acute large-vessel occlusion stroke. Beyond clear clinical benefits in the acute and post-acute phases, comprehensive evaluations of long-term outcomes, including home and workforce reintegration, remain limited. This study aimed to assess home and workforce reintegration 1 year post-EVT in a cohort of acute stroke patients and explore their association with health-related quality of life (HRQoL). We conducted a prospective observational study of 404 patients undergoing EVT at a tertiary university medical center between October 2019 and December 2021. Patients' functional outcomes were evaluated using the modified Rankin Scale (mRS), and HRQoL was assessed via the European Quality of Life Five Dimension Scale (EQ-5D). Data on occupational and living status were collected through standardized telephone interviews at 3- and 12-months post-treatment. Of 357 patients with 12-month follow-up data, 33.6% had a favorable outcome (mRS 0-2). Among stroke survivors, the rate of home reintegration without nursing care was 42.1%, and workforce reintegration among previously employed patients was 43.3% at 12 months. Both outcomes were significantly associated with improved HRQoL. Lower neurological deficits and younger age were predictive of successful home and workforce reintegration. One year post-EVT, approximately 40%-50% of acute stroke patients successfully reintegrate into home and work settings. These findings underscore the need for ongoing support tailored to improving long-term reintegration and quality of life for stroke survivors. The data supporting the findings of the study are available from the corresponding author upon reasonable request and in accordance to European data privacy obligations.

Indwelling Urological Device Biofilm Composition and Characteristics in the Presence and Absence of Infection

ObjectiveTo characterize microbial biofilms associated with different device types used in the urological field including ureteral stents, sacral neuromodulation (SNM) devices, penile prostheses, and artificial urinary sphincters (AUS). Materials and MethodsData from four studies, each reporting biofilm composition of a particular device type, were pooled and included for inter-device analysis. Studies recruited adults scheduled for ureteral stent, SNM, IPP, or AUS removal/revision. Device (n=115) biofilms and controls were analyzed with multi-omics approaches, and compositions were compared across device types and clinical factors. ResultsMicrobiota present on each device type was distinct from that of perineal, rectal, or urine flora (p<0.01). Biofilm microbial counts (p<0.001) and diversity (p=0.024) differed by device type. Ureteral stents had greater microbial counts than other device types (p<0.001). Staphylococcus, Pseudomonas, Lactobacillus, Ureaplasma were commonly detected across devices. Device biofilms harbored a greater proportion of Proteobacteria phylum, and the rectal, perineal, and urine flora harbored a greater proportion of Firmicutes. Unique microbe-metabolite interaction networks were identified in presence and absence of infection. Antibiotic resistance genes including sul2 (sulfonamide resistance) and rpoB (rifampin resistance) were detected in biofilms across device types. Biofilm reconstitution in vitro differed by device type from which strains were isolated. ConclusionsUreteral stents, sacral neuromodulation devices, penile prostheses, and artificial urinary sphincters harbored unique microbial and metabolite profiles that differed from those of skin, urine, and rectal flora. The findings of this study set the groundwork for investigation of novel strategies to reduce device-associated infection risk within and outside urology. Data availability statementData are available from corresponding author upon reasonable request.

Transition from Acute to Chronic Low Back Pain in a Community-Based Cohort

The transition from acute to chronic low back pain (LBP) in community settings is not well understood. The purpose of this study was to assess the feasibility of recruitment and estimate the transition and continuation of chronic LBP. We also explored characteristics associated with this transition to chronic LBP. We enrolled n=131 participants, of which n=118 (90%) completed 3-month outcomes and n=111 (85%) completed 6-month outcomes. Acute LBP was defined by a duration of <4 weeks and a 30-day LBP-free period before the current acute episode. Chronic LBP was defined as pain most or every day over the past 3 months. The transition from acute to chronic LBP at 3 months was 32.2% (38/118), and at 6 months, 80.6% (25/31) of participants who transitioned at 3 months continued to have chronic LBP at 6 months. Participants with more frequent acute LBP and at an intensity of 30/100 were more likely to transition to chronic LBP (Risk Ratio (RR)=3.13, 95% Confidence Interval (CI) 1.84, 5.30) and continue to have chronic LBP at 6-months (RR=3.10, 95% CI 1.48, 6.08). Higher risk on the STarT Back Screening Tool was associated with the transition to chronic LBP at 3 months (RR=1.73, 95% CI 1.28, 2.35) and continuation of chronic LBP at 6 months (RR=1.26, 95% CI 1.10, 1.45). The recruitment of acute LBP was feasible in a community setting. Acute LBP is a common condition in the community and frequently transitions to chronic LBP, suggesting the potential for substantial burden in the community. PerspectiveThis article presents the feasibility of conducting a community-based study to describe the transition, continuation, and psychosocial predictors of acute to chronic low back pain. These findings could help identify community participants at high risk of incident and continued chronic low back pain. Data AvailabilityThe data that support the findings of this study are available from the corresponding author, [AG], upon reasonable request.

A lifetime economic model of mortality and secondary care use for patients discharged from hospital following acute stroke.

The long-term health-economic consequences of acute stroke are typically extrapolated from short-term outcomes observed in different studies, using models based on assumptions about longer-term morbidity and mortality. Inconsistency in these assumptions and the methods of extrapolation can create difficulties when comparing estimates of life-time cost-effectiveness of stroke care interventions. To develop a long-term model consisting of a set of equations to estimate the life-time effects of stroke care interventions to promote consistency in extrapolation of short-term outcomes. Data about further admissions and mortality was provided for acute stroke patients discharged between 2013 and 2014 from a large English service. This was combined with data from UK life tables to create a set of parametric equations in a model that use age, sex, and modified Rankin Scores to predict the life-time risk of mortality and secondary care resource utilisation including ED attendances, non-elective admissions, and elective admissions. A cohort of 1,509 (male 51%; mean age 74) stroke patients had median follow-up of seven years and represented 7,111 post-discharge patient years. A logistic model estimated mortality within twelve months of discharge and a Gompertz model was used over the remainder of the lifetime. Hospital attendances were modelled using a Weibull distribution. Non-elective and elective bed days were both modelled using a log-logistic distribution. Mortality risk increased with age, dependency, and male sex. Although the overall pattern was similar for resource utilisation, there were different variations according to dependency and gender for ED attendances and non-elective/elective admissions. For example, 65-year-old women with a discharge mRS of 1 would gain an extra 6.75 life years compared to 65-year-old women with a discharge mRS of 3. Over their lifetime, 65-year-old women with a discharge mRS of 1 would experience 0.09 less ED attendances, 2.12 less non-elective bed days and 1.28 additional elective bed days than 65-year-old women with a discharge mRS of 3. Using long-term follow-up publicly available data from a large clinical cohort, this new model promotes standardised extrapolation of key outcomes over the life course, and potentially can improve the real-world accuracy and comparison of long-term cost-effectiveness estimates for stroke care interventions. Data is available upon reasonable request from third parties.

Early penumbral FLAIR changes predict tissue fate in patients with large vessel occlusions.

In patients with an acute ischemic stroke, the penumbra is defined as ischemic tissue that remains salvageable when reperfusion occurs. However, the expected clinical recovery congruent with penumbral salvage, is not always observed. We aimed to determine if the Magnetic Resonance Imaging (MRI) defined penumbra includes irreversible neuronal loss that impedes expected clinical recovery after reperfusion. In the prospective French Acute Multimodal Imaging Study to Select Patients for Mechanical Thrombectomy (FRAME) and an observational cohort of patients with large vessel occlusions undergoing endovascular treatment, we quantified penumbral integrity by FLAIR changes. We studied the influence of recanalization status on the evolution of penumbral FLAIR changes and studied penumbral FLAIR changes as predictor of tissue fate and functional outcome on the 90 days modified Rankin Scale (mRS). Recanalization status did not modify the evolution of rFLAIR signal intensity (SI) over time in the total cohort, but was associated with lower SI in the FRAME subset (b=-0.06, p for interaction=0.04). Median rFLAIR SI was higher at baseline in the subsequently infarcted penumbra compared to the salvaged (ratio=1.07, standard deviation [SD] 0.07 vs 1.03, SD 0.06 p<0.0001, n=150). The severity and extent of rFLAIR SI changes did not predict 90 day functional outcome in univariate (p=0.09) and multivariate logistic regression (p=0.4). Recanalization status did not influence the evolution of penumbral FLAIR changes. FLAIR SI changes in the baseline penumbra were associated with tissue fate, but not functional outcome. The data supporting the study are available upon reasonable request; following a signed data access agreement.

The treatment effect across ASPECTS in acute ischemic stroke: Analysis from the AcT trial.

Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication. We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase and Alteplase. Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0-1, mRS 0-2, and ordinal mRS at 90 days. Safety outcomes included 24-h symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed-effects logistic regression was used to assess the association of ASPECTS (continuous and categorical (0-4 vs 5-7 vs 8-10)) with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity. Of the 1577 patients in the trial, 901 patients (56.3%; median age 75 years (IQR 65-84), 50.8% females, median National Institute of Health Stroke Scale (NIHSS) 14 (IQR 17-19)) with anterior circulation stroke were included. mRS 0-1 at 90 days was achieved in 1/14 (0.3%), 43/160 (14.7%), and 252/726 (85.1%) in the ASPECTS 0-4, 5-7, and 8-10 groups respectively. Every one-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0-1 and mRS 0-2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in endovascular thrombectomy (EVT)-treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0-1 (P-interaction 0.75). There was no significant interaction by thrombolytic type with any other outcomes. Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase. Data shall made available on reasonable request from the PI (BMM).

Temporal trends and practice variation in early repair of the ruptured aneurysm among patients with aneurysmal subarachnoid hemorrhage in the United States, 2012-2019.

Early repair of the ruptured cerebral aneurysm (RRCA), preferably within 24 h of onset, is endorsed by clinical guideline as the preferred management strategy for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, a comprehensive picture of this guideline-recommended usage in contemporary clinical practice is not available. This study aimed to characterize trends over time and practice variation in the implementation of an early RRCA strategy among patients with aSAH in a large, national representative data. Using data from the 2012-2019 National Inpatient Sample, we measured trends in the proportion of early RRCA, defined as within day 1 of admission, overall, and by demographic and geographical subgroups. In addition, we created multilevel regression models to quantify hospital-level variation in the early RRCA rates. We identified 82,615 aSAH hospitalizations (mean age = 56.1 years; 68.9% women) undergoing RRCA and, among these, 84.0% (95% confidence interval (CI) = 83.4-84.7%) receiving early RRCA. The proportion of early RRCA increased steadily from 82.5% in 2012 to 85.8% in 2019 (p for trend <0.001). The proportion of patients receiving early RRCA across geographic regions ranged from 78.7% to 87.9%, with a median (interquartile range (IQR)) of 84.2% (83.0-86.1%). In contrast, the delivery of early RRCA varied widely among hospitals, with a median (IQR) rate of 86.1% (75.0-100.0%) and a range from 0% to 100.0%. The median odds ratio for the early use of RRCA treatment was 1.24 (95% CI = 1.21-1.27) in 2019, indicating 24% increased odds of implementing early RRCA if moving from a lower-use to a higher-use hospital. Most patients in the United States with aSAH received early RRCA treatment and exhibited an upward trend over the recent 8-year period. However, substantial variation in access to early RRCA was observed across population subgroups, particularly at the hospital level. Future efforts are necessary to identify further sources of this variation and to develop initiatives that could represent an opportunity to optimize guideline-based quality of care in aSAH management. The data are available from the corresponding author upon reasonable request following completion of onboarding and verification procedures as specified by the HCUP.

Focusing on tumor and it’s microenvironmental immune members for head and neck cancer patients

ObjectiveImmune-related gene expression levels in the tumor microenvironment (TM) of head and neck squamous cell carcinoma (HNSCC) patients was compared. Materials and methodsThe CD163, CD274, CD86, FUT4, FOXP3, and ITGAX levels of HNSCC patients in their tumor tissues (n =76) and surrounding tissues adjacent to the tumor (n =76) were determined using quantitative real-time PCR (qRT-PCR). Changes in these genes were also evaluated by associating with demographical data of the patients. ResultsCD163, CD274, FUT4, and FOXP3 gene expression levels were significantly higher in tumor tissue than in surrounding tissue. FUT4 fold change was statistically higher in patients with lymph node involvement. CD86 expression was statistically lower in smokers of 50 boxes per year or more. CD163, CD274, and FUT4 expressions were increased in response to the presence of extranodal extension (ENE). ConclusionsThese preliminary results demonstrate the alterations in expression levels of immunologic markers are associated with the clinical presentations of HNSCC. Availability of data and materialsThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Bending performance of lightweight aggregate concrete beam subjected to reinforcement corrosion: Experimental and numerical study

The application of lightweight aggregate concrete (LWAC) benefits the structural behavior of long-span and high-rise buildings. However, the corrosion-related durability issue of bending elements made of LWAC has remained unresolved for decades, and the bending performance of corroded LWAC beam, including load-bearing capacity, stiffness, cracking, and etc., has not yet been clearly defined due to limited knowledge in the available literature. This study aims to investigate the bending performance of LWAC beams subjected to reinforcement corrosion, and the test results provide valuable data for addressing the research gap relevant to the topic and contribute fundamental knowledge to the promotion of structural LWAC elements. Seven reinforced LWAC beams were tested to examine the cracking behavior, characteristic loads and deflections, deformation ability, and distribution of cross section strain at various moments. The modelling method considering the effect of rebar corrosion for LWAC beam was proposed. It was concluded that the corrosion of longitudinal rebar led to decreased cracking, yielding, and ultimate moment of LWAC beam, while the corrosion of stirrups increased the cracking moment and had little effects on the yielding and ultimate moments. The ductility of the tested specimens initially decreased and then increased with the raising corrosion level of the longitudinal rebar, which was attributed to the variation in bond performance between the rebar and LWAC. All tested beams exhibited a yielding deflection smaller than 1/235 of the span length. The strain distribution of the mid-span cross-section exhibited a nonlinear feature with increasing mass loss of the corroded longitudinal steel rebar. The proposed modelling procedure considering the corrosion effect showed good agreement with the test results, and a preliminary analysis of the bending performance of LWAC beams with different steel reinforcement corrosion ratios was completed. Data Availability StatementAll data, models, or code that support the findings of this study are available from the corresponding author upon reasonable request.

Use of pressure muscle index to guide pressure support ventilation setting: a study protocol and statistical plan for a prospective randomised controlled proof-of-concept trial

IntroductionAlthough pressure support ventilation is one of the most commonly used assisted ventilation modes in intensive care units, there is still a lack of precise strategies for setting pressure support....

Comparative study on pharmacokinetics of extract from Bufonis venenum and its liposomes

Bufadienolides and indolealkylamines, the primary active components in Bufonis venenum, have rapid clearance from the body with a short half-life, leading to low bioavailability. Moreover, Bufadienolides and indolealkylamines are associated with serious adverse effects. In order to reduce the toxicities, minimize the adverse effects and simultaneously load lipophilic bufadienolides and hydrophilic indolealkylamines with satisfactory drug loading and encapsulation rate, we prepared Bufonis venenum extract-liposomes (BVE-LP). To compare the pharmacokinetic differences between Bufonis venenum extract (BVE) and its liposomes, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay was established to simultaneously detect the 12 chemical components in rat plasma. Results of pharmacokinetic study in SD rats showed that the highest exposure based on the area under the plasma concentration-time curve (AUC0-t) was obtained by 5-hydroxytryptamine with a mean value of 267.097 μg/L*h in BVE-LP group, which was 72.36 % higher as compared to that obtained in Bufonis venenum extract (BVE) group with a mean value of AUC0-t of 154.966 μg/L*h. The exposure (AUC0-t) of desacetylcinobufotalin, desacetylcinobufagin, arenobufagin and telocinobufagin in BVE-LP group was 111.89 %, 94.13 %, 134.08 %, and 92.94 % higher when compared to that in BVE group. With the employment of liposomes, there was an obvious decrease in the clearance of bufotenidine, desacetylcinobufotalin, gamabufotalin, arenobufagin, and telocinobufagin. The terminal half life (t1/2) of desacetylcinobufotalin, gamabufotalin, arenobufagin, and telocinobufagin in BVE-LP group was increased by 185.96 %, 292.64 %, 196.78 % and 131.29 % when compared to that in BVE group. All the results above indicated that a slower elimination rate and more exposure of some bufadienolides and indolealkylamines was obtained by BVE-LP when compared to BVE group, which verified BVE-LP could provide a therapeutic option for effective delivery of Bufonis venenum in clinical. Data availabilityThe data will be shared on reasonable request to the corresponding author.

Vertical non-uniform distribution of soil salinity enhances nitrogen utilization efficiency and influences δ15N distribution in tomato plants

Soil salinity typically exhibits non-uniform distribution in the natural environment. However, how vertically non-uniform distribution of soil salinity in the root zone (VNDSR) regulated plant nitrogen metabolism is still largely elusive. This study aimed to investigate the impact of VNDSR on leaf Malondialdehyde (MDA) content, upper and lower root activity, leaf Na+/Ca2+ and Na+/K+, various tomato organs’ nitrogen concentration (%) and natural abundance of nitrogen isotopes (δ15N,‰), and nitrogen utilization efficiency of tomato plants. Four treatments were established, including the upper layer of the root zone having soil salinity levels of 1 ‰, 1 ‰, 2 ‰, and 3 ‰, while the corresponding lower layer of the root zone had soil salinity levels of 1 ‰, 5 ‰, 4 ‰, and 3 ‰, respectively, denoted as T1:1, T1:5, T2:4, and T3:3. The results showed that under the same average soil salinity conditions and compared to the treatment with uniform soil salinity distribution in the root zone (T3:3), the VNDSR treatment (T1:5) significantly reduced leaf MDA content (p < 0.01), Na+/Ca2+ (p < 0.01) and Na+/K+ (p < 0.01), and stem δ15N values (p < 0.05). Moreover, the VNDSR treatment (T1:5) significantly increased the ratio of upper and lower root biomass-weighted root activity (p < 0.01), tomato fruit yield (p < 0.01), and nitrogen partial factor productivity (PFP, gg−1, p < 0.01) compared to uniform salt distribution treatment (T3:3). There were significant positive correlations (p < 0.05) between leaf δ15N values and Nitrogen Absorption Ratio (NAR, %, p < 0.05) and PFP (p < 0.05), indicating that under VNDSR, δ15N values can serve as an indicator that comprehensively reflects the information of plant nitrogen utilization efficiency. In conclusion, the VNDSR could mitigate the damage of salt stress to tomatoes, enhance plant nitrogen uptake and utilization efficiency, and promote the growth and development of tomatoes. Data AvailabilityThe datasets generated or analyzed during the current study are available from the corresponding author on reasonable request.

Expression profiles of miRNAs in the lung tissue of piglets infected with Glaesserella parasuis and the roles of ssc-miR-135 and ssc-miR-155–3p in the regulation of inflammation

MicroRNAs (miRNAs) have been shown to play an important regulatory role in the process of pathogenic infection. However, the miRNAs that regulate the pathogenic process of G. parasuis and their functions are still unknown. Here, high-throughput sequencing was used to quantify the expression of miRNA in piglet lung tissue after G. parasuis XX0306 strain infection. A total of 25 differentially expressed microRNAs (DEmiRNAs) were identified. GO and KEGG pathway enrichment analysis showed that many of the functions of genes that may be regulated by DEmiRNA are related to inflammatory response and immune regulation. Further studies found that ssc-miR-135 may promote the expression of inflammatory factors through NF-κB signaling pathway. Whereas, ssc-miR-155–3p inhibited the inflammatory response induced by G. parasuis, and its regulatory mechanism remains to be further investigated. This study provides a valuable reference for revealing the regulatory effects of miRNAs on the pathogenesis of G. parasuis. Data AvailabilityThe datasets generated during the current study are not publicly available due to this study is currently in the ongoing research stage, and some of the data cannot be made public sooner yet, but are available from the corresponding author on reasonable request.

A double-masked, sham-controlled trial of rose bengal photodynamic therapy for the treatment of fungal and acanthameoba keratitis: Rose Bengal Electromagnetic Activation with Green Light for Infection Reduction (REAGIR) Study.

Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro Rose Bengal Photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates.22,23 In one published series RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthameoba keratitis not responsive to medical therapy. This international, randomized, sham and placebo controlled 2-arm clinical trial, randomizes patients with smear positive fungal and acanthameoba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) Topical antimicrobial plus sham RB-PDT or 2) Topical antimicrobial plus RB-PDT. We anticipate that RB-PDT will improve best spectacle corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via clinicaltrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. NCT, NCT05110001, Registered November 5, 2021. https://www.clinicaltrials.gov/study/NCT05110001.

Insulin resistance and white matter microstructural abnormalities in nondiabetic adult: A population-based study.

Insulin resistance (IR) is of growing concern yet its association with white matter integrity remains controversial. We aimed to investigate the association between IR and white matter integrity in nondiabetic adults. This cross-sectional analysis was conducted based on the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study. A total of 1709 nondiabetic community-dwelling adults with available diffusion-weighted imaging based on brain magnetic resonance imaging and completed oral glucose tolerance test were included. IR was measured noninvasively by insulin sensitivity indices (ISI), including ISIcomposite and ISI0,120, as well as homeostasis model assessment of insulin resistance (HOMA-IR). White matter microstructure abnormalities were identified by diffusion-weighted imaging along with tract-based spatial statistical analysis to compare diffusion metrics between groups. The multivariable linear regression models were applied to measure the association between white matter microstructure abnormalities and IR. A total of 1709 nondiabetic individuals with a mean age of 60.8 ± 6.4 years and 54.1% female were included. We found that IR was associated with a significant increase in mean diffusivity, axial diffusivity, and radial diffusivity extensively in cerebral white matter in regions such as the anterior corona radiata, superior corona radiata, anterior limb of internal capsule, external capsule, and body of corpus callosum. The pattern of associations was more marked for ISIcomposite and ISI0,120. However, the effect of IR on white matter integrity was attenuated after, in addition, adjustment for history of hypertension and cardiovascular disease and antihypertensive medication use. Our findings indicate a significant association between IR and white matter microstructural abnormalities in nondiabetic middle-aged community residents, while these associations were greatly influenced by the history of hypertension and cardiovascular disease, and antihypertensive medication use. Further investigation is needed to clarify the role of IR in white matter integrity, whereas prophylactic strategies of maintaining a low IR status may ameliorate disturbances in white matter integrity. The data that support the findings of this study are available from the corresponding authors upon reasonable request.

Endovascular treatment to improve outcomes for medium vessel occlusions: The ESCAPE-MeVO trial.

Clinical outcomes in acute ischemic stroke due to medium vessel occlusion (MeVO) are often poor when treated with best medical management. Data from non-randomized studies suggest that endovascular treatment (EVT) may improve outcomes in MeVO stroke, but randomized data on potential benefits and risks are hitherto lacking. Thus, there is insufficient evidence to guide EVT decision-making in MeVO stroke. The primary aim of the ESCAPE-MeVO trial is to demonstrate that acute, rapid EVT in patients with acute ischemic stroke due to MeVO results in better clinical outcomes compared to best medical management. Secondary outcomes are to demonstrate the safety of EVT, its impact on self-reported health-related quality of life, and cost-effectiveness. Based on previously published data, we estimate a sample size of 500 subjects to achieve a power of 85% with a two-sided alpha of 0.05. To account for potential loss to follow-up, 530 subjects will be recruited. ESCAPE-MeVO is a multicenter, prospective, randomized, open-label study with blinded endpoint evaluation (PROBE design), clinicaltrials.gov: NCT05151172. Subjects with acute ischemic stroke due to MeVO meeting the trial eligibility criteria will be allocated in a 1:1 ratio to best medical care plus EVT versus best medical care only. Patients will be screened only at comprehensive stroke centers to determine if they are eligible for the trial, regardless of whether they were previously treated at a primary care center. Key eligibility criteria are (1) acute ischemic stroke due to MeVO that is clinically and technically eligible for EVT, (2) last-known well within the last 12 h, (3) National Institutes of Health Stroke Scale > 5 or 3-5 with disabling deficit, (4) high likelihood of salvageable tissue on non-invasive neuroimaging. The primary outcome is the modified Rankin scale 90 days after randomization (shift analysis), whereby modified Rankin Score 5 and 6 will be collapsed into one category. Secondary outcomes include dichotomizations of the modified Rankin Score at 90 days, 24 h National Institutes of Health Stroke Score, difference between 24 h and baseline National Institutes of Health Stroke Score, mortality at 90 days, health-related quality of life (EQ-5D-5 L), Lawton scale of instrumental activities of daily living score, reperfusion quality (MeVO expanded Thrombolysis in Cerebral Infarction Score) and infarct volume at 24 h, and cost-effectiveness of endovascular recanalization. Safety outcomes include symptomatic and asymptomatic intracranial hemorrhage and procedural complications. The ESCAPE-MeVO trial will demonstrate the effect of endovascular thrombectomy in addition to best medical management vis-à-vis best medical management in patients with acute ischemic stroke due to MeVO and provide data for evidence-based treatment decision-making in acute MeVO stroke. The raw data discussed in this mansucript will be made available by the corresponding author upon reasonable request.

Predictors of Futile Recanalization in Ischemic Stroke Patients with low baseline NIHSS.

There is yet no randomized controlled evidence that mechanical thrombectomy (MT) is superior to best medical treatment in patients with large vessel occlusion but minor stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] <6). Prior studies of patients with admission NIHSS scores >6 observed unfavorable functional outcomes despite successful recanalization, commonly termed as futile recanalization (FR), in up to 50% of cases. The aim of this study is to determine the prevalence of FR in patients with minor stroke and identify associated patient-specific risk factors. Our multicenter cohort study screened all patients prospectively enrolled in the German Stroke Registry Endovascular Treatment from 2015 to 2021 (n=13082). Included were patients who underwent MT for anterior circulation vessel occlusion with a baseline NIHSS score of <6 and successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3). FR was defined by a modified Rankin Scale (mRS) score of 2-6 at 90 days. Multivariable logistic regression analysis was conducted to explore factors associated with FR. A total of 674 patients met the inclusion criteria. FR occurred in 268 (40%) patients. Multivariable logistic regression analysis indicates that higher age (adjusted odds ratio: 1.04 [95% confidence interval: 1.02-1.06]), pre-stroke mRS 1 (aOR: 2.70 [1.51-4.84]), transfer from admission hospital to comprehensive stroke center (aOR: 1.67 [1.08-2.56]), longer time from symptom onset/last seen well to admission (aOR: 1.02 [1.00-1.04]), MT under general anesthesia (aOR: 1.78 [1.13-2.82]), higher NIHSS after 24 hours (aOR: 1.09 [1.05-1.14]), and symptomatic intracranial hemorrhage (aOR: 16.88 [2.03-140.14]) increased the odds of FR. There was no significant difference in primary outcome between achieving mTICI 2b or 3. Unfavorable functional outcomes despite successful vessel recanalization were frequent in acute ischemic stroke patients with low NIHSS scores on admission. We provide patient-specific risk factors that indicate an increased risk of FR and should be considered when treating patients with minor stroke. The data that support the findings of our study are available on reasonable request after approval of the GSR steering committee.