Aim: Although a lower level of non-high-density lipoprotein cholesterol (HDL-C) was reported to be inversely associated with spontaneous intracranial hemorrhage (ICH), no enough evidence has verified ...whether lipid profiles modify hemorrhagic transformation and functional outcomes in patients with acute ischemic treated with thrombolysis.Methods: This multicenter cohort study included 2373 patients with acute ischemic stroke treated with intravenous thrombolysis between December 2004 and December 2016. Of these, 1845 patients were categorized into either the hyperlipidemia or non-hyperlipidemia group. Symptomatic ICH (SICH) rates within 24-36 h of thrombolytic onset and functional outcomes at 30 and 90 days were longitudinally surveyed. Models of predicting hemorrhagic transformation were used to validate our findings.Results: For enrolled 1845 patients, SICH rates were ≥2-fold reduced for the hyperlipidemia group by the NINDS (adjusted RR: 0.488 0.281–0.846, p=0.0106), the ECASS II (adjusted RR: 0.318 0.130-0.776, p=0.0119), and SITS-MOST standards (adjusted RR: 0.214 0.048-0.957, p=0.0437). The favorable functional rates between the two groups were not significantly different. Lower levels of LDL-C were showed in robust association with SICH. With a cut-off LDL-C value of ＜130 mg/dL, new models are more robust and significant in predicting hemorrhagic transformation within 24-36 h.Conclusions: This study supports the strong association between reduced LDL-C and increased SICH, but not for functional outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. LDL-C level of ＜130 mg/dL is supposed to a candidate marker for predicting SICH within 24-36 h.
To compare surgical outcomes between 27 and 25-gauge vitrectomy in proliferative diabetic retinopathy (PDR) with tractional retinal detachment (TRD).
This retrospective study was conducted to compare ...the intraoperative status, operation time, use of instruments, endotamponade substance, wound suture number, and iatrogenic break, between 27 and 25-gauge vitrectomy in 43 eyes afflicted by PDR with TRD. The post-surgical results, best-corrected visual acuity, intraocular pressure, recurrent vitreous haemorrhage, and re-operation rate were regularly followed up for 6 months.
Patients in the 25 and the 27-gauge groups did not differ significantly in terms of pre-surgical conditions, such as age, gender, pre-existing glaucoma, best-corrected visual acuity (BCVA) and the severity of their TRD. The mean operation time was 56.7 minutes in the 27-gauge group and 63.7 minutes in the 25-gauge group (p = 0.94). There is significantly less use of micro forceps in the 27-gauge group (p = 0.004). No difference between micro scissors and chandelier usage were noted; neither was their difference in iatrogenic retinal breaks. Significantly fewer wound sutures were noted in the 27-gauge group (p < 0.001). The post-operative results revealed no significant difference in ocular hypertension, hypotony, BCVA improvement, recurrent vitreous haemorrhage and re-operation rate.
The 27-gauge vitrectomy system offers comparable surgical outcomes in PDR with TRD. The 27-gauge vitrectomy system is suitable for complicated retinal surgery.
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is a powerful low density lipoprotein cholesterol (LDL-C)-lowering therapy, but this drug is expensive. This study aimed to ...describe the real-world treatment conditions in patients initiating PCSK9 inhibitor in Taiwan.Methods: This was a multicenter, retrospective, and observational study. The clinical characteristics, baseline lipid-lowering therapy, and changes in the lipid profile of patients receiving PCSK9 inhibitor treatment were obtained from 11 major teaching hospitals in Taiwan.Results: A total of 296 patients (age 57±13 years, male 73%) who received PCSK9 inhibitor treatments (73.3% alirocumab and 26.7% evolocumab) from 2017 to 2021 were included. Among the patients, 62.8% had history of coronary artery disease, and 27.7% had myocardial infarction. High intensity statin (HIS) monotherapy or HIS＋ezetimibe treatment was used in 32.5% when initiating PCSK9 inhibitor treatment. Among alirocumab users, 21.2% received 75 mg every 3 to 4 weeks, whereas among evolocumab users, 8.9% received 140 mg every 3 to 4 weeks. Almost all the non-standard-dosing PCSK9 inhibitors were paid by the patients themselves but were not reimbursed by the Taiwan National Health Insurance. Overall, the LDL-C levels at baseline and 12 weeks after treatment were 147.4±67.4 and 69.7±58.2 mg/dL (p＜0.01), corresponding to a 49.6%±31.8% LDL-C reduction.Conclusions: In the real-world practice in Taiwan, the LDL-C reduction efficacy of PCSK9 inhibitors was slightly lower than that reported in the clinical trials. The use of non-standard-dosing PCSK9 inhibitors was not uncommon in Taiwan.
In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of ...adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer's disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.
Enterohemorrhagic Escherichia coli (EHEC) induces changes to the intestinal cell cytoskeleton and formation of attaching and effacing lesions, characterized by the effacement of microvilli and then ...formation of actin pedestals to which the bacteria are tightly attached. Here, we use a Caenorhabditis elegans model of EHEC infection to show that microvillar effacement is mediated by a signalling pathway including mitotic cyclin-dependent kinase 1 (CDK1) and diaphanous-related formin 1 (CYK1). Similar observations are also made using EHEC-infected human intestinal cells in vitro. Our results support the use of C. elegans as a host model for studying attaching and effacing lesions in vivo, and reveal that the CDK1-formin signal axis is necessary for EHEC-induced microvillar effacement.
Water ingress is one of the major environmental stresses to cause the degradation of device performance in organic photovoltaic (OPVs) and is one of the major barriers impeding their ...commercialization. This work demonstrates that combining the use of a nanoparticle titanium dioxide (np‐TiO2) electron transporting layer (ETL) and an all‐polymer bulk heterojunction (BHJ) photoactive layer can endow the derived OPV with a much better water resistivity than the commonly employed zinc oxide (ZnO) ETL or polymer:small molecule BHJ blends. Polymer donors/acceptors are first shown to possess better water‐immersion than the small molecule counterparts. Hence, the all‐polymer blend exhibits the lowest absorbance losses after water immersion among the studied BHJ systems. Furthermore, the result reveals that tailoring the structure of the TiO2 ETL from planar to nanoparticles effectively strengthens the adhesion at the ETL/BHJ interface to prevent physical delamination. Finally, the np‐TiO2/all‐polymer blend (half‐cell) is demonstrated to have superior stability under water immersion, i.e., unchanged morphology and charge carrier transfer, as well as no efficiency changes in the complete cells. This work demonstrates the great potential of the all‐polymer blends and np‐TiO2 ETL for improving the durability of unencapsulated OPVs under high humidity environments and even water immersion.
The underwater stability of organic photovoltaics is successfully enhanced through a systematic water‐insensitive engineering of organic photoactive layers and electron‐transporting layers. The all‐polymer blend film exhibits the lowest absorbance losses after water immersion among studied bulk‐heterojunction systems. Substituting ZnO with TiO2 can achieve a more stable morphology after water immersion, and tailoring the nanostructure of TiO2 from planar to nanoparticle can better strengthen its adhesion with the all‐polymer blend to prevent physical delamination.
Background Insufficient evidence is available for patients with acute ischemic stroke with atrial fibrillation (AF) to determine the efficacy and safety of different dosages of intravenous ...thrombolysis treatment. This study examined clinical outcomes in Chinese patients with stroke with and without AF after intravenous thrombolysis treatment with different intravenous thrombolysis doses. Methods and Results This multicenter, prospective cohort study recruited 2351 patients with acute ischemic stroke (1371 with AF and 980 without AF) treated with intravenous thrombolysis using alteplase. The Totaled Health Risks in Vascular Events score is a validated risk-scoring tool used for assessing patients with acute ischemic stroke with and without AF. We evaluated favorable functional outcome at day 90 and symptomatic intracranial hemorrhage within 24 to 36 hours and outcomes of the patients receiving different doses of alteplase. Compared with the non-AF group, the AF group exhibited a 2- to 3-fold increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (relative risk RR, 2.10 95% CI, 1.35-3.26). Favorable functional outcome at 90 days and symptomatic intracranial hemorrhage rates according to the European Cooperative Acute Stroke Study II and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study standards did not significantly differ between the AF and non-AF groups. In addition, the low-dose alteplase subgroup exhibited an increased risk of symptomatic intracranial hemorrhage according to the National Institute of Neurological Disorders and Stroke standard (RR, 2.84 95% CI, 1.63-4.96). A validation study confirmed these findings after adjustment for scores determined using different stroke risk-scoring tools. Conclusions Different alteplase dosages did not affect functional status at 90 days in the AF and non-AF groups. Thus, the adoption of low-dose alteplase simply because of AF is not recommended.
Objective
To evaluate human glymphatics and meningeal lymphatics noninvasively.
Methods
This prospective study implemented 3‐dimensional (3D) isotropic contrast‐enhanced T2 fluid‐attenuated inversion ...recovery (CE‐T2‐FLAIR) imaging with a 3T magnetic resonance machine to study cerebral glymphatics and meningeal lymphatics in patients with reversible cerebral vasoconstriction syndrome (RCVS) with (n = 92) or without (n = 90) blood–brain barrier (BBB) disruption and a diseased control group with cluster headache (n = 35). The contrast agent gadobutrol (0.2mmol/kg 0.2ml/kg) was administered intravenously in all study subjects.
Results
In total, 217 patients (182 RCVS, 35 cluster headache) were analyzed and separated into 2 groups based on the presence or absence of visible gadolinium (Gd) leakage. Para‐arterial tracer enrichment was clearly depicted in those with overt BBB disruption, while paravenous and parasinus meningeal contrast enrichment was evident in both groups. Paravenous and parasinus contrast enrichment remained in RCVS patients in the remission stage and in cluster headache patients, suggesting that these meningeal lymphatic channels were universal anatomical structures rather than being phase‐ or condition‐specific. Additionally, we demonstrated nodular leptomeningeal enhancement in 32.3% of participants, which might represent potential lymphatic reservoirs. Four selected RCVS patients who received consecutive contrasted 3D isotropic FLAIR imaging after gadobutrol administration showed that the Gd persisted for at least 54 minutes and was completely cleared within 18 hours.
Interpretation
This large‐scale in vivo study successfully demonstrated the putative human para‐arterial glymphatic transports and meningeal lymphatics by clear depiction of para‐arterial, parasinus, and paravenous meningeal contrast enrichment using high‐resolution 3D isotropic CE‐T2‐FLAIR imaging noninvasively; this technique may serve as a basis for further studies to delineate clinical relevance of glymphatic clearance. ANN NEUROL 2021;89:111–124
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