Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke.

BACKGROUND: Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied. METHODS: In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days. RESULTS: A total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03). CONCLUSIONS: Among patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).

Ultralow-Friction at Cryogenic Temperature Induced by Hydrogen Correlated Quantum Effect.

Temperature is one of the governing factors affecting friction of solids. Undesired high friction state has been generally reported at cryogenic temperatures due to the prohibition of thermally activated processes, following conventional Arrhenius equation. This has brought huge difficulties to lubrication at extremely low temperatures in industry. Here, the study uncovers a hydrogen-correlated sub-Arrhenius friction behavior in hydrogenated amorphous carbon (a-C:H) film at cryogenic temperatures, and a stable ultralow-friction over a wide temperature range (103-348 K) is achieved. This is attributed to hydrogen-transfer-induced mild structural ordering transformation, confirmed by machine-learning-based molecular dynamics simulations. The anomalous sub-Arrhenius temperature dependence of structural ordering transformation rate is well-described by a quantum mechanical tunneling (QMT) modified Arrhenius model, which is correlated with quantum delocalization of hydrogen in tribochemical reactions. This work reveals a hydrogen-correlated friction mechanism overcoming the Arrhenius temperature dependence and provides a new pathway for achieving ultralow friction under cryogenic conditions.

A Pilot Study to Assess the Suitability of Riboflavin as A Surrogate Marker of Breast Cancer Resistance Protein (BCRP) in Healthy Participants.

We recently showed that riboflavin is a selected substrate of BCRP over P-gp and demonstrated its prediction performance in preclinical DDI studies. The aim of this study was to investigate the suitability of riboflavin to assess BCRP inhibition in humans. First, we assessed the substrate potential of riboflavin towards other major drug transporters using established transfected cell systems. Riboflavin is a substrate for OAT1, OAT3, and MATE2-K with uptake ratios ranging from 2.69 to 11.6 but riboflavin is not a substrate of OATP1B1, OATP1B3, OCT2, and MATE1. The effects of BMS-986371, a potent in vitro inhibitor of BCRP (IC 50 0.40 µM), on the pharmacokinetics of riboflavin, isobutyryl carnitine, and arginine were then examined in healthy male adults (N = 14 or 16) following oral administration of methotrexate (MTX) (7.5 mg) and enteric coated (EC) sulfasalazine (SSZ) (1,000 mg) alone or in combination with BMS-986371 (150 mg). Oral administration of BMS-986371 increased the AUCs of rosuvastatin and immediate-release (IR) SSZ to 1.38- and 1.51-fold , respectively, and significantly increased AUC(0-4h), AUC(0-24h), and C max of riboflavin by 1.25-, 1.14-, and 1.11-fold (P-values of 0.003, 0.009, and 0.025, respectively) compared to the MTX/SSZ EC alone group. In contrast, BMS-986371 did not significantly influence the AUC(0-24h) and C max values of isobutyryl carnitine and arginine (0.96- to 1.07-fold, respectively; P > 0.05). Overall, these data indicate that plasma riboflavin is a promising biomarker of BCRP that may offer a possibility to assess drug candidate as a BCRP modulator in early drug development. Significance Statement Endogenous compounds that serve as biomarkers for clinical inhibition of BCRP are not currently available. This study provides the initial evidence that riboflavin is a promising BCRP biomarker in humans. For the first time, the value of leveraging the substrate of BCRP with acceptable prediction performance in clinical studies is shown. Additional clinical investigations with known BCRP inhibitors are needed to fully validate and showcase the utility of this biomarker.

Smokers with Elevated Glycated Albumin Could Not Benefit from Dual Antiplatelet Therapy after Minor Stroke or Transient Ischemic Attack.

INTRODUCTION: The aim of this study was to investigate the impact of smoking on dual antiplatelet therapy in patients with minor stroke or transient ischemic attack (TIA) under different glycated albumin (GA) levels. METHODS: We analyzed data from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A subgroup of 3,044 patients with baseline GA levels was included and categorized by smoking status and GA levels. The primary efficacy outcome was a new stroke within 90 days. The safety outcome was any bleeding event at 90 days. The interaction of smoking status with antiplatelet therapy was calculated by Cox proportional hazards regression model. RESULTS: In patients with GA levels ≤15.5%, the proportion of smokers was 37.7% (719/1,908), while in patients with GA levels >15.5%, it was 51.6% (586/1,136). During the 3-month follow-up period, 299 (9.9%) patients had a new stroke occurrence. In patients with elevated GA levels, both smokers and nonsmokers could not benefit from dual antiplatelet therapy (smokers, adjusted hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.42-1.17; nonsmokers, adjusted HR 0.82, 95% CI: 0.57-1.18). In patients with normal GA levels, dual antiplatelet therapy reduced the risk of stroke recurrence in smokers by 72% (adjusted HR 0.28, 95% CI: 0.14-0.56) and in nonsmokers by 53% (adjusted HR 0.47, 95% CI: 0.26-0.86). However, whether the GA level was elevated or normal, there was no significant interaction between smoking status and antiplatelet therapy. CONCLUSIONS: Smokers with elevated GA levels could not benefit from dual antiplatelet therapy after minor stroke or TIA.

Seed pretreatment with brassinosteroids stimulates sunflower immunity against parasitic weed (Orobanche cumana) infection.

Broomrape (Orobanche cumana) negatively affects sunflower, causing severe yield losses, and thus, there is a need to control O. cumana infestation. Brassinosteroids (BRs) play key roles in plant growth and provide resilience to weed infection. This study aims to evaluate the mechanisms by which BRs ameliorate O. cumana infection in sunflower (Helianthus annuus). Seeds were pretreated with BRs (1, 10, and 100 nM) and O. cumana inoculation for 4 weeks under soil conditions. O. cumana infection significantly reduced plant growth traits, photosynthesis, endogenous BRs and regulated the plant defence (POX, GST), BRs signalling (BAK1, BSK1 to BSK4) and synthesis (BRI1, BR6OX2) genes. O. cumana also elevated the levels of malondialdehyde (MDA), hydroxyl radical (OH-), hydrogen peroxide (H2O2) and superoxide (O2 •-) in leaves/roots by 77/112, 63/103, 56/97 and 54/89%, as well as caused ultrastructural cellular damages in both leaves and roots. In response, plants activated a few enzymes, superoxide dismutase (SOD), peroxidase (POD) and reduced glutathione but were unable to stimulate the activity of ascorbate peroxidase (APX) and catalase (CAT) enzymes. The addition of BRs (especially at 10 nM) notably recovered the ultrastructural cellular damages, lowered the production of oxidative stress, activated the key enzymatic antioxidants and induced the phenolic and lignin contents. The downregulation in the particular genes by BRs is attributed to the increased resilience of sunflower via a susceptible reaction. In a nutshell, BRs notably enhanced the sunflower resistance to O. cumana infection by escalating the plant immunity responses, inducing systemic acquired resistance, reducing oxidative or cellular damages, and modulating the expression of BR synthesis or signalling genes.

Subthreshold micropulse laser therapy for early postoperative macular thickening following surgical removal of epiretinal membrane.

BACKGROUND: This study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal. METHODS: This was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed. RESULTS: An improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 µm vs. -45.0 ± 46.9 µm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 µm vs. -19.7 ± 16.3 µm, P = 0.547) or 3-month (-36.9 ± 26.9 µm vs. -34.0 ± 20.1 µm, P = 0.678) follow-up. CONCLUSIONS: SMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery. TRIAL REGISTRATION: The study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).

Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case.

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

The effects of different doses of lanthanum-modified bentonite in combination with a submerged macrophyte (Vallisneria denseserrulata) on phosphorus inactivation and macrophyte growth: A mesocosm study.

The combination of chemical phosphorus (P) inactivation and submerged macrophyte transplantation has been widely used in lake restoration as it yields stronger effects than when applying either method alone. However, the dose effect of chemical materials on P inactivation when used in combination with submerged macrophytes and the influences of the chemicals used on the submerged macrophytes growth remain largely unknown. In this study, we investigated P inactivation in both the water column and the sediment, and the responses of submerged macrophytes to Lanthanum modified bentonite (LMB) in an outdoor mesocosm experiment where Vallisneria denseserrulata were transplanted into all mesocosms and LMB was added at four dosage levels, respectively: control (LMB-free), low dosage (570 g m-2), middle dosage (1140 g m-2), and high dosage (2280 g m-2). The results showed that the combination of LMB dosage and V. denseserrulata reduced TP in the water column by 32%-38% compared to V. denseserrulata alone, while no significant difference was observed among the three LMB treatments. Porewater soluble reactive P, two-dimensional diffusive gradient in thin films (DGT)-labile P concentrations, and P transformation in the 0-1 cm sediment layer exhibited similar trends along the LMB dosage gradient. Besides, LMB inhibited plant growth and reduced the uptake of mineral elements (i.e., calcium, manganese, iron, and magnesium) in a dosage-dependent manner with LMB. LMB may reduce plant growth by creating a P deficiency risk for new ramets and by interfering with the uptake of mineral elements. Considering both the dose effect of LMB on P inactivation and negative effect on macrophyte growth, we suggest a "small dosage, frequent application" method for LMB application to be used in lake restoration aiming to recover submerged macrophytes and clear water conditions.

Evaluation of combined epiretinal membrane removal with intravitreal triamcinolone injection utilizing ectopic inner foveal layer staging scheme.

OBJECTIVE: To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme. METHODS: Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups. RESULTS: After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10). CONCLUSION: Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM.

Prevalence and Risk Factors of Cerebral Small Vessel Disease from a Population-Based Cohort in China.

INTRODUCTION: Cerebral small vessel disease (CSVD) is a significant burden of morbidity and mortality among elderly people around the world. Epidemiological data with complete CSVD evaluations and a large sample size in the general population are still limited. METHODS: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study were included in this study from 2017 to 2019. All participants underwent 3 Tesla brain magnetic resonance images to assess CSVD imaging markers. Demographic and risk factor data were collected. The general and age-specific prevalence of lacune, confluent white matter hyperintensity (WMH), moderate-severe enlarged perivascular spaces (EPVS), cerebral microbleed (CMB), and total CSVD score (an ordinal scale from 0 to 4, counting the presence of four imaging markers of CSVD) was evaluated. Associations between vascular risk factors and these markers were analyzed by multivariable logistic regression. RESULTS: A total of 3,063 participants were enrolled. The mean age was 61.2 years and 46.5% were men. The most prevalent CSVD marker was confluent WMH (16.7%), followed by CMB (10.2%), moderate-severe EPVS in the basal ganglia (BG-EPVS) (9.8%), and lacune (5.6%). 30.5% of the participants have at least one of the four markers (total CSVD score ≥1 points). The prevalence of CSVD markers increases as age increases. Age and hypertension were independent risk factors for four CSVD markers and the total CSVD score. CONCLUSIONS: In this Chinese cohort with community-based adults aged 50-75 years, our findings showed a prevalence of 30.5% for CSVD. The most prevalent CSVD marker was confluent WMH, followed by CMB, moderate-severe BG-EPVS, and lacune. The risk factors for CSVD must be strictly screened and controlled in adults living in the community.

Association of intracranial atherosclerosis with cerebral small vessel disease in a community-based population.

BACKGROUND AND PURPOSE: The purpose of this study was to explore the relationship between intracranial atherosclerosis and cerebral small vessel disease (CSVD). METHODS: Community-dwelling residents of Lishui, China in the PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study were involved. Intracranial atherosclerosis was grouped by the severity of intracranial artery plaques with stenosis and burden. Four imaging markers including lacunes, white matter hyperintensity (WMH), cerebral microbleeds (CMBs), and perivascular spaces (PVS) as well as the CSVD burden scores were assessed. Logistic regression or ordinal logistic regression models with odds ratio (OR) or common OR (cOR) were used to estimate the relationship between intracranial atherosclerosis and CSVD markers and burdens. RESULTS: The mean age was 61.20 ± 6.68 years, and 1424 (46.52%) were men among 3061 participants included at baseline. Intracranial atherosclerotic burden was associated with the severity of the lacunes (OR = 4.18, 95% confidence interval [CI] = 1.83-9.58), modified WMH burden (cOR = 1.94, 95% CI = 1.01-3.71), presence of CMBs (OR = 2.28, 95% CI = 1.05-4.94), and CMB burden (OR = 2.23, 95% CI = 1.03-4.80). However, it was not associated with the WMH burden and PVS. Intracranial atherosclerotic burden was associated with CSVD burden (Wardlaw: cOR = 2.73, 95% CI = 1.48-5.05; Rothwell: cOR = 2.70, 95% CI = 1.47-4.95). The association between intracranial atherosclerosis and CSVD was obvious in participants with both anterior and posterior circulation artery stenosis. CONCLUSIONS: Based on a Chinese community population, there may be an association between intracranial atherosclerosis and CSVD, but its mechanism in relation to vascular risk factors still needs to be clarified.

Aminotransferase Level and the Effects of Dual Antiplatelet in Minor Stroke or Transient Ischemic Attack: A post hoc Analysis of a Randomized Control Trial.

INTRODUCTION: This study was intended to evaluate whether the safety and efficacy of dual antiplatelet treatment in patients with minor ischemic stroke (MIS) or transient ischemic attack (TIA) could be modified by the aminotransferase level. Also, we sought to assess the interaction between aminotransferase level and CYP2C19 loss-of-function status on the efficacy of dual antiplatelet therapy. METHODS: This study is a post hoc analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) study, a double-blinded randomized control trial. We included 5,133 patients with a complete workup of baseline alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The primary outcome is stroke or TIA recurrence within 90 days. Cox proportional hazard models were used in the evaluation of the efficacy of antiplatelet treatment in patients with different aminotransferase levels and subgroups categorized by the aminotransferase level × CYP2C19 loss-of-function status. RESULTS: The median age of all the included patients was 62 years; 66.3% of the patients were male. More recurrent stroke or TIA occurred in patients with elevated ALT and AST levels within 90 days compared to patients with normal ALT and AST levels (14.5 vs. 11.2%, p = 0.029). Dual antiplatelet treatment with aspirin and clopidogrel reduced recurrence compared with aspirin alone in patients with both normal (adjusted hazard ratio [HR], 95% confidence interval [CI]: 0.72 [0.60-0.86], p < 0.001) and elevated (adjusted HR [95% CI]: 0. 57 [0. 35-0. 92], p = 0. 020) ALT and AST levels (p = 0.64 for interaction). No significant difference in treatment efficacy on 90-day all-cause death or bleeding events was found. CONCLUSIONS: Dual antiplatelet treatment was safe for minor stroke or high-risk TIA patients with mildly elevated aminotransferase. Mild elevation of ALT or AST did not undermine the protective efficacy of the dual antiplatelet regimen in reducing recurrent stroke or TIA within 90 days after MIS or TIA. The interaction between the CYP2C19 loss-of-function allele carrier status and aminotransferase level on the efficacy of dual antiplatelet treatment was not observed.

Sexual Compulsivity Mediates the Association Between Childhood Sexual Abuse and Condom Use Resistance Among Men Who Have Sex with Men and Women.

Despite the continued prevalence of HIV and condoms' proven effectiveness in HIV prevention, many young men continue to engage in condom use resistance (CUR). Research shows that sexual compulsivity and childhood sexual abuse (CSA) victimization are risk factors for CUR. Given that sexual activity between men is the most common method through which HIV is transmitted, and that men who have sex with men and women (MSMW) are up to five times as likely to contract or transmit HIV as men who have sex with women only (MSWO), understanding the CUR behaviors of MSMW is uniquely important. Young, single men who had had sex with a woman in the past year (N = 623) completed questionnaires assessing their previous sexual experiences with men and women, history of CSA, sexual compulsivity, and CUR to determine how MSMW classification may moderate the associations between these variables. Results revealed full, moderated mediation, such that CSA was significantly associated with sexual compulsivity among MSMW, but not MSWO. Furthermore, sexual compulsivity was subsequently associated with CUR, in a model accounting for 5.35% of CUR variance. Such findings suggest that exposure to CSA may render MSMW especially susceptible to maladaptive, sexually compulsive desires and behaviors. As a result, MSMW may be more likely to disregard the inherent risks associated with condomless sexual activity and engage in CUR. Thus, intervention programs seeking to reduce the transmission of HIV and other STIs should prioritize targeting MSMW who experienced CSA to reduce sexual compulsivity and increase condom use.

Predicting reintervention after thoracic endovascular aortic repair of Stanford type B aortic dissection using machine learning.

OBJECTIVES: To construct models for predicting reintervention after thoracic endovascular aortic repair (TEVAR) of Stanford type B aortic dissection (TBAD). METHODS: A total of 192 TBAD patients who underwent TEVAR were included; 68 (35.4%) had indications for reintervention. Clinical characteristics, aorta characteristics on pre- and postoperative computed tomography angiography, and aorta characteristics on immediate postoperative aortic digital subtraction angiography were collected. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify the risk factors for reintervention. Eight classifiers were used for modeling. The models were trained on 100 train-validation random splits with a ratio of 2:1. The performance was evaluated by the receiver operating characteristic curve. RESULTS: Seven predictors of reintervention were identified, including maximum false lumen diameter, aortic diameter measured at the level of approximately 15 mm distal to the left subclavian artery, aortic diameter measured at the level of the diaphragm, false lumen diameter measured at the level of the celiac artery, number of bare-metal and covered stents, number of bare-metal stents, and residual perfusion of the false lumen. Logistic regression (LR) yielded the highest performance, with an area under the curve of 0.802. A nomogram built for clinical use showed good calibration. The cutoff value for dividing patients into low- and high-risk subgroups was 0.413. Kaplan-Meier curves showed that the overall survival of high-risk patients was significantly shorter than that of low-risk patients (both p < 0.05). CONCLUSION: Our nomogram could predict the reintervention after TEVAR in patients with TBAD, which may facilitate patient selection and surveillance strategies. KEY POINTS: • Seven risk factors of reintervention after TEVAR of TBAD were identified for modeling. • Logistic regression performed best in predicting reintervention with an AUC of 0.802. • Patients with a high risk of reintervention had shorter OS than those with a low risk.

Genetically predicted childhood obesity and adult atrial fibrillation: A mendelian randomization study.

BACKGROUND AND AIMS: It is unclear whether the association of childhood obesity with adult atrial fibrillation observed in observational studies reflects causal effects. The aim of this study was to evaluate the association of childhood obesity with adult atrial fibrillation using genetic instruments. METHODS AND RESULTS: We used a two-sample Mendelian randomization (MR) design to evaluate the association between childhood obesity and adult atrial fibrillation. Two sets of genetic variants (15 single nucleotide polymorphisms [SNPs] for childhood body mass index [BMI] and 12 SNPs for dichotomous childhood obesity) were selected as instruments. Summary data on SNP-childhood obesity and SNP-atrial fibrillation associations were obtained from recently published genome-wide association studies. Effect estimates were evaluated using inverse-variance weighted (IVW) methods. Other MR analyses, including MR-Egger, simple and weighted median, weighted MBE and MR-PRESSO methods were performed in sensitivity analyses. The IVW models showed that both a genetically predicted one-standard deviation increase in childhood BMI (kg/m2) and higher log-odds of childhood obesity were associated with a substantial increase in the risk of atrial fibrillation (OR = 1.22, 95% CI: 1.11-1.34, P < 0.001; OR = 1.09, 95% CI: 1.04-1.14, P < 0.001). MR-Egger regression showed no evidence of genetic pleiotropy for childhood BMI (intercept = 0.000, 95% CI: -0.024 to 0.023), but for childhood obesity (intercept = -0.036, 95% CI: -0.057 to -0.015). Similar results were observed using leave-one-out and other MR methods in sensitivity analyses. CONCLUSIONS: This MR analysis found a consistent association between genetically predicted childhood obesity and an increased risk of adult atrial fibrillation. Further research is warranted to validate our findings.

COMPARISON OF INTERNAL LIMITING MEMBRANE PEELING WITH THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR RHEGMATOGENOUS RETINAL DETACHMENT COEXISTING WITH MACULAR HOLE.

PURPOSE: To evaluate the anatomical and functional outcomes of internal limiting membrane (ILM) peeling and the inverted ILM flap technique for rhegmatogenous retinal detachment coexisting with macular hole. METHODS: This retrospective study evaluated the medical records of 79 eyes with concurrent rhegmatogenous retinal detachment and macular hole received vitrectomy and silicone oil tamponade, with ILM peeling on 56 eyes and the inverted ILM flap technique on 23 eyes. RESULTS: The Type 1 closure rate was greater in the inverted ILM flap group than the ILM peeling group (82.6% vs. 55.4%, P = 0.038). Lines of improvement were 7.8 ± 5.3 in the ILM peeling group and 8.9 ± 5.6 in the inverted ILM flap group. Postoperative epiretinal membrane and retinal reattachment rates were similar in two surgical groups (16.1% vs. 21.7%, P = 0.535 and 94.6% vs. 95.7%, P = 0.999, respectively). Type 1 closure was significantly correlated with the inverted ILM flap technique (OR = 5.568, P = 0.023). The inverted ILM flap technique showed no significant association with the final logarithm of the minimum angle of resolution best-corrected visual acuity in multivariate model analysis. CONCLUSION: The inverted ILM flap technique was more effective in restoring the macular structure in patients with rhegmatogenous retinal detachment and coexisting macular hole, but the functional outcomes of the two strategies were comparable.

Anatomical and visual outcomes of fovea-sparing internal limiting membrane peeling with or without inverted flap technique for myopic foveoschisis.

BACKGROUND: Vitrectomy and peeling of the internal limiting membrane (ILM) was an effective therapeutic approach for myopic foveoschisis with progressive visual loss. This study investigated the anatomical and visual outcomes of fovea-sparing ILM peeling with or without the inverted flap technique for patients with symptomatic myopic foveoschisis (MF). METHODS: We retrospectively reviewed the clinical data of patients with MF. Vitrectomy with fovea-sparing ILM peeling and air tamponade was performed in all patients. The primary outcome measures included best-corrected visual acuity (BCVA), mean macular thickness (MMT), and central foveal thickness (CFT). Depending on whether an inverted ILM flap technique was utilized, further subgroup comparisons between the inverted flap group and the non-inverted flap group were conducted. RESULTS: Twenty-six eyes of 22 patients were included. Fifteen eyes were underwent fovea-sparing ILM peeling without inverted ILM flap and 11 of the 26 eyes were treated with fovea-sparing ILM peeling and an inverted ILM flap technique. In the mean follow-up period of 10.74 ± 4.58 months, a significant improvement in BCVA was observed from 0.97 ± 0.45 logMAR to 0.58 ± 0.51 logMAR (P < 0.01), during which the BCVA of 20 eyes (76.92%) improved and remained stable in 5 eyes (19.23%). Moreover, a positive correlation was also found between the preoperative BCVA and the postoperative BCVA (r = 0.50, P = 0.01). At the last visit, the final MMT decreased from 492.69 ± 209.62 µm to 234.73 ± 86.09 µm, and the CFT reduced from 296.08 ± 209.22 µm to 138.31 ± 73.92 µm (all P < 0.01). A subgroup analysis found no significant differences in BCVA, MMT, or CFT between the inverted and non-inverted flap groups (all P > 0.05). CONCLUSION: Fovea-sparing ILM peeling with or without inverted flap technique resulted in favorable visual and anatomical outcomes for the treatment of MF. An important factor affecting the postoperative visual outcome was the preoperative visual acuity. Our study found no significant difference between the presence and absence of the inverted ILM flap.

Diabetic retinopathy with extensively large area of capillary non-perfusion: characteristics and treatment outcomes.

BACKGROUND: Capillary non-perfusion is an important characteristic for diabetic retinopathy (DR) indicating microvascular damage and ischemia. Data on the description and treatment outcomes of DR with large area of non-perfusion are lacking to date. We aim to describe the characteristics and treatment outcomes in a series of patients with DR who presented extensively large area of capillary non-perfusion (LACNP). METHODS: Fundus fluorescein angiograms from medical charts in patients diagnosed with DR between Jan 2017 and Dec 2019 were retrospectively reviewed. Clinical data in eyes with LACNP including imaging and laboratory findings at the first presentation were analyzed. The LACNP was defined as over 70% area of capillary non-perfusion throughout the whole image retina. The mean follow-up duration was 12.4 ± 16.7 months. Follow-up data including extensive pan-retinal photocoagulation and surgical intervention and treatment outcomes were evaluated. RESULTS: A total of 43 eyes in 24 patients with LACNP were included, accounting for 3.3% of DR populations in the same period. The overall percentage of non-perfusion area was 79.1 ± 8.1%. All patients received proper control of diabetes and hypertension, and extensive pan-retinal laser photocoagulation. During the follow-up periods, 20 eyes (46.5%) developed severe neovascular complications, of which 15 eyes (34.9%) underwent vitrectomy and/or anti-glaucoma surgeries. Conservative therapies including glycemic control and supplemental laser photocoagulation were conducted in 23 eyes (53.5%) without neovascular complications. In the final follow-up, best corrected visual acuity improved or maintained stable in 19 eyes (44.2%) while deteriorated in 24 eyes (55.8%). CONCLUSIONS: The presence of LACNP is the hallmark of advanced DR and often indicates a poor visual outcome, although aggressive treatments may slow DR progression and maintain central vision for some time.

Detection of Airborne Nanoparticles through Enhanced Light Scattering Images.

A new method is proposed in this paper to detect airborne nanoparticles, detecting the light scattering caused by both the particle and the surrounding molecules, which can surpass the limitations of conventional laser optical methods while maintaining simplicity and cost-effectiveness. This method is derived from a mathematical analysis that describes the particle light scattering phenomenon more exactly by including the influence of light scattered from surrounding gas molecules. The analysis shows that it is often too much of a simplification to consider only light scattering from the detected nanoparticle, because light scattering from the surrounding gas molecules, whether visible or invisible to the sensor, is important for nanoparticle detection. An image detection approach utilizing the light scattering from surrounding air molecules is described for the detection of airborne nanoparticles. Tests using monodisperse nanoparticles confirm that airborne particles of around 50 nm in size can even be detected using a low-cost testing device. This shows further that even when using a simple image processing code, captured particle light scattering images can be converted digitally into instantaneous particle counts or concentrations. The factors limiting conventional pulse detection are further discussed. This new method utilizes a simple static light scattering (SLS) approach to enable the development of new devices with better detection capabilities, paving the way for the further development of nanoparticle detection technology.

Aspirin platelet reactivity on platelet function and clinical outcome in minor stroke or transient ischemic attack.

OBJECTIVE: Whether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial. MATERIALS AND METHODS: Patients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y12 assay for P2Y12 reaction units (PRU); HPR to P2Y12 was defined as >208 PRU (poor response to P2Y12). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days. RESULTS: Among 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y12 responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y12 responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20-4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%). CONCLUSIONS: In patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.