Efficacy and safety of Brolucizumab for neovascular age-related macular degeneration: a systematic review and meta-analysis.

Background: To evaluate the efficacy and safety of Brolucizumab for neovascular age-related macular degeneration (n-AMD) through a systematic review and meta-analysis. Materials and Methods: Cochrane, PubMed, Embase, and Web of Science databases were comprehensively searched for relevant studies. Stata and RevMan5.4 were applied for meta-analysis and risk of bias assessment. Data on the best-corrected visual acuity (BCVA), central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), participants with ≥1 serious adverse events, and participants with ≥1 adverse events were analyzed. Results: Six studies were finally included. Meta-analysis showed statistical differences in BCVA [SMD = -0.65, 95% CI [-0.17 to -0.23], P < 0.05], the presence of IRF and/or SRF [RR = 0.67, 95% CI [0.56-0.79], P < 0.05], and the safety of participants with ≥1 serious adverse events [RR = 0.57, 95% CI [0.39-0.84], P < 0.05] between the experimental group and the control group. However, no statistical differences were observed in CSFT [SMD = -1.16, 95% CI [-2.79 to 0.47], P > 0.05] or the safety of participants with ≥1 adverse events [RR = 1.07, 95% CI [0.97-1.17], P > 0.05]. Conclusions: Compared to other anti-VEGF drugs such as Aflibercept and Ranibizumab, intravitreal injection of 6 mg Brolucizumab is more effective and safer for n-AMD, especially in the presence of IRF and/or SRF, and for participants with ≥1 serious adverse events.

Evaluation of retinal structural and functional changes after silicone oil removal in patients with rhegmatogenous retinal detachment: a retrospective study.

BACKGROUND: To evaluate retinal structural and functional changes after silicone oil (SO) removal in eyes with macula-off rhegmatogenous retinal detachment (RRD). METHODS: Best-corrected visual acuity (BCVA) testing, microperimetry, and optical coherence tomography angiography were performed in 48 eyes with macula-off RRD before and 3 months after SO removal. The values of healthy contralateral eyes were used as control data. Correlations between retinal vessel density (VD), retinal nerve fiber layer thickness (RNFLT), the interval between retinal detachment and surgery, the duration of SO tamponade, the follow-up time after SO removal, and visual function were analyzed. RESULTS: Significant increases in 2˚ fixation rate (FR), 4˚ FR, 2˚ mean retinal sensitivity (MRS), 6˚ MRS, parafoveal superficial capillary plexus VD and RNFLT were observed after SO removal (all P < 0.05). The increase of 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade and the follow-up time after SO removal respectively (all P < 0.05). The last 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade, the interval between retinal detachment and surgery, and the follow-up time after SO removal (all P < 0.01). The last FR in RRD eyes was close to that of contralateral eyes (P > 0.05). CONCLUSION: Retinal structure and function improved to different degrees after SO removal. Fixation stability and retinal sensitivity increased more than BCVA postoperatively. Retinal sensitivity, which was affected by the interval between retinal detachment and surgery and the duration of SO tamponade, gradually recovered after SO removal.

How are N-methylcarbamates encapsulated by ß-cyclodextrin: insight into the binding mechanism.

Guest molecules containing chromophore groups encapsulated by ß-cyclodextrin (ß-CD) generate circular dichroism (CD) signals, which enables a preliminary prediction of their binding modes. However, the accurate determination of the representative binding conformation (RC) remains a challenging task due to the complex conformational space of these host-guest systems. Here, we combine a molecular dynamics/quantum mechanics/continuum solvent model (MD/QM/CSM) with induced circular dichroism (ICD) data (N. L. Pacioni, A. B. Pierini and A. V. Veglia, Spectrochim. Acta A Mol. Biomol. Spectrosc., 2013, 103, 319-324.) to explore the binding mechanism of ß-CD with four N-methylcarbamate molecules: promecarb (PC), bendiocarb (BC), carbaryl (CY) and carbofuran (CF). In aqueous solution, their stability decreases as: PC > BC > CY > CF. Comparing the ECD spectra computed from TD-DFT with the ICD data can help eliminate many common binding configurations and identify the RC. The host-guest binding affinities (BAs) estimated using a ONIOM2(B971:PM6)/SMD model reproduce the measured binding trend, reveal the competition between the non-covalent interaction and solvent effect and explain the large difference in their binding modes. We also examine the fluctuations in the computed BA using similar structures.

A self-learning cognitive architecture exploiting causality from rewards.

Inspired by the human vision system and learning, we propose a novel cognitive architecture that understands the content of raw videos in terms of objects without using labels. The architecture achieves four objectives: (1) Decomposing raw frames in objects by exploiting foveal vision and memory. (2) Describing the world by projecting objects on an internal canvas. (3) Extracting relevant objects from the canvas by analyzing the causal relation between objects and rewards. (4) Exploiting the information of relevant objects to facilitate the reinforcement learning (RL) process. In order to speed up learning, and better identify objects that produce rewards, the architecture implements learning by causality from the perspective of Wiener and Granger using object trajectories stored in working memory and the time series of external rewards. A novel non-parametric estimator of directed information using Renyi's entropy is designed and tested. Experiments on three environments show that our architecture extracts most of relevant objects. It can be thought of as 'understanding' the world in an object-oriented way. As a consequence, our architecture outperforms state-of-the-art deep reinforcement learning in terms of training speed and transfer learning.

Enhanced mechanical properties and biocompatibility on BC/HAp composite through calcium gluconate fortified bacterial.

Bacterial cellulose/hydroxyapatite (BC/HAp) composite is an outstanding candidate for bone tissue engineering. The conventional biomimetic mineralization method takes a long time with unsatisfactory mechanical properties and biocompatibility. Herein, we modified the BC by changing the carbon source to calcium gluconate during the biosynthesis process of BC by bacteria, providing nucleation sites for further mineralization in simulated body fluid. Results show spherical porous HAp in the size of 100-200 nm was fully filled in the three-dimensional network structure of BC nanofibers uniformly within five days of mineralization. Molecular dynamics simulation shows that the aggregation of cellulose units in aqueous solution can enhance the adsorption of calcium ions. By this means, we significantly improved the mechanical properties and biocompatibility of the BC/HAp composite, as well as simplified the preparation process, compared to conventional method, which, therefore, suggests, it could be further studied for biomedical applications such as bone tissue engineering.

Peripapillary changes after vitrectomy and silicone oil tamponade for rhegmatogenous retinal detachment.

PURPOSE: To evaluate the peripapillary changes after vitrectomy and silicone oil (SO) tamponade in eyes with rhegmatogenous retinal detachment (RRD). METHODS: In this study, 25-gauge vitrectomy with SO tamponade was performed in 22 eyes with RRD. The radial peripapillary capillary (RPC) vessel density (VD) and retinal nerve fiber layer thickness (RNFLT) were assessed by optical coherence tomography angiography at 2, 4, 8, and 12 weeks postoperatively. The values of healthy fellow eyes were used as controls. RESULTS: The global RPC VDs were significantly lower in the eyes with RRD than in fellow healthy eyes at 2 weeks (P < 0.001), and increased at 4 weeks, then decreased over time after surgery (F = 1.046, P = 0.377). The RPC VDs in the superior-hemifield were lower than those in the inferior-hemifield at 12 weeks postoperatively (t = -2.844, P = 0.010). The global RNFLTs decreased gradually after vitrectomy in the eyes with RRD (F = 1.312, P = 0.276). The RNFLTs in the superior-hemifield were thinner than those in the inferior-hemifield at 12 weeks postoperatively (t = -2.222, P = 0.037). The global, superior, and inferior RNFLTs were correlated with corresponding RPC VDs in the eyes with RRD at all time-points postoperatively (P < 0.05). CONCLUSION: RRD resulted in the decrease of RPC VDs. The RPC VDs recovered in the early postoperative period but were still lower than the normal level. Long-term application of SO tamponade resulted in the reduction of peripapillary VDs secondary to loss of RNFLTs.

In silico analysis of novel dipeptidyl peptidase-IV inhibitory peptides released from Macadamia integrifolia antimicrobial protein 2 (MiAMP2) and the possible pathways involved in diabetes protection.

The aim of the present study was to screen novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from Macadamia integrifolia antimicrobial protein 2 (MiAMP2) and evaluate the potential antidiabetic targets and involved signaling pathways using in silico approaches. In silico digestion of MiAMP2 with pepsin, trypsin and chymotrypsin was performed with ExPASy PeptideCutter and the generated peptides were subjected to BIOPEP-UWM, iDrug, INNOVAGEN and Autodock Vina for further analyses. Six novel peptides EQVR, EQVK, AESE, EEDNK, EECK, and EVEE were predicted to possess good DPP-IV inhibitory potentials, water solubility, and absorption, distribution, metabolism, excretion, and toxicity properties. Molecular dynamic simulation and molecular docking displayed that AESE was the most potent DPP-IV inhibitory peptide and can bind with the active sites of DPP-IV through hydrogen bonding and van der Waals forces. The potential antidiabetic targets of AESE were retrieved from SwissTargetPrediction and GeneCards databases. Protein-protein interaction analysis identified BIRC2, CASP3, MMP7 and BIRC3 to be the hub targets. Moreover, the KEGG pathway enrichment analysis showed that AESE prevented diabetes through the apoptosis and TNF signaling pathways. These results will provide new insights into utilization of MiAMP2 as functional food ingredients for the prevention and treatment of diabetes.

Risk factors of recurrent acute pancreatitis after conservative treatment in pediatric population: a single-center study.

Background: Although complete resolution and recovery occurs in most children with an initial attack of acute pancreatitis (AP), a subset of children may progress to recurrent AP (RAP). RAP has serious effects to the individual and the socioeconomic burden. The aim of this project was to identify the independent risk factors for pediatric RAP so as to provide evidence for its prevention, early diagnosis and treatment. Methods: A retrospective cohort study of children discharged from Tianjin Children's Hospital from June 2017 to January 2020 was performed. Demographic and clinical variables, treatment strategies, clinical course and outcomes were collected. Independent risk factors of RAP were identified using the logistic regression model. Results: Of the total 96 enrolled children, 30 (31.3%) developed RAP during the follow-up period. The majority (27/30, 90%) of the children with AP developed RAP within 6 months of their first AP attack. The presence of systemic inflammatory response syndrome (SIRS) [odds ratio (OR)=6.652, 95% confidence interval (CI) 1.989 to 22.247], fasting time (OR=1.267, 95% CI 1.104 to 1.583), whether meet all three AP diagnostic criteria (OR=7.438, 95% CI 1.346 to 41.103) and abnormal amylase/lipase value on the seventh day of hospitalization (OR=3.601, 95% CI 0.972 to 13.342) were independent risk factors of RAP in children. Conclusions: Most children who developed RAP had progressed within 6 months after their first episode of AP. RAP was more common in children who met all three AP diagnostic criteria at initial attack and in children with SIRS, long fasting time and abnormal amylase/lipase value on the seventh day of hospitalization.

Relevant factors for early liver transplantation after Kasai portoenterostomy.

BACKGROUND: To explore the relevant factors for early liver transplantation (LT) after Kasai portoenterostomy (KP). METHODS: Retrospective analysis was performed for 200 children with biliary atresia, who underwent LT with hepatic failure after KP. According to the interval between KP and LT, they were divided into three groups: G1 (≤6-month), G2 (6-month~ 2-year) and G3 (> 2-year). Gender, age of Kasai portoenterostomy, jaundice-clearance, cholangitis after KP and liver function indexes before LT were compared among the three groups. RESULTS: The proportion of patients with age of KP (≤90-day) in G1 was lower than that in G3 (P = 0.003). Jaundice-clearance occurred in 6 (7.6%), 26(28.6%) and 26 (86.7%) patients after KP in G1, G2 and G3 respectively (P < 0.001). There were statistical differences in the incidence of early cholangitis, late cholangitis and repeated cholangitis among the three groups (P = 0.035, < 0.001 and 0.022). The native liver survival (NLS) rate of children at operation age > 90-day was lower than that of children at operation age ≤ 90-day (P = 0.002). The NLS rate of the children with jaundice-clearance after KP was significantly better than that of the children without jaundice-clearance (P < 0.001). The NLS rate of the children with early cholangitis after operation was lower than that in children without early cholangitis (P = 0.026). The NLS rate of patients of G2 and G3 with cholangitis after KP was lower than that in children without cholangitis (P = 0.017). Multiple logistic regression analysis showed uncleared jaundice after KP was a risk factor for the NLS time in patients. CONCLUSION: The age of KP (> 90-day), jaundice-unclear and early cholangitis could reduce the NLS time after KP, which were related to early liver transplantation. Jaundice-unclear was a risk factor for early liver transplantation.