Placebo Effect and Its Determinants in Ocular Hypotensive Therapy: Meta-analysis and Multiple Meta-regression Analysis.

TOPIC: The placebo effect and its potential determinants in ocular hypotensive therapy. CLINICAL RELEVANCE: The placebo effect has been studied and documented within a wide clinical context. It remains unclear whether placebo is effective in glaucoma treatment or, if so, which factors are determinative of effect size (ES). METHODS: Randomized controlled trials (RCTs) of topical ocular hypotensive therapy for patients with open-angle glaucoma or ocular hypertension, conducted through June 2, 2022, were included. First, a perceived placebo effect was measured as the overall intraocular pressure (IOP) change from the baseline. It was evaluated in terms of the ES (mean difference between the baseline and the end point) and then was compared with the ES, as obtained from the untreated control participant to obtain a true placebo effect. The primary outcome was ES based on 4 weeks of treatment. Meta-analysis-based statistical pooling was performed where appropriate, and 95% confidence intervals (CIs) were used for comparison. Potential placebo effect determinants were scrutinized using a multiple meta-regression model (PROSPERO identifier, CRD42022348098). RESULTS: A total of 40 RCTs (7829 eyes) with 33 placebo groups (2055 eyes) along with 7 untreated groups (1184 eyes) were included. Among placebo-controlled trials, placebo was determined to be effective in lowering IOP (ES, -1.30 mmHg; 95% CI, -1.75 to -0.84 mmHg). Using NMA, the ES for placebo was -2.27 mmHg (95% CI, -3.52 to -1.01 mmHg) greater than ES for untreated control participants.. According to the multiple meta-regression model, the active treatment ES was a significant factor to predict the amount of placebo effect. Placebo additionally lowered IOP by -0.45 mmHg per -1 mmHg of active treatment effect. Add-on study design and larger sample size also were associated with greater amount of placebo effect. No publication bias was evident in either a funnel plot or the Begg and Mazumdar adjusted rank correlation test results (P = 0.24). DISCUSSION: This meta-analysis indicated that placebo is effective in lowering IOP and is superior to the effect observed for the untreated control participants. However, caution is required in interpreting the results because of the small number of untreated controlled trials and potential bias from the lack of direct comparison between the placebo and untreated arms. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Robust Indoor Localization Methods Using Random Forest-Based Filter against MAC Spoofing Attack.

With the development of wireless networks and mobile devices, interest on indoor localization systems (ILSs) has increased. In particular, Wi-Fi-based ILSs are widely used because of the good prediction accuracy without additional hardware. However, as the prediction accuracy decreases in environments with natural noise, some studies were conducted to remove it. So far, two representative methods, i.e., the filtering-based method and deep learning-based method, have shown a significant effect in removing natural noise. However, the prediction accuracy of these methods severely decreased under artificial noise caused by adversaries. In this paper, we introduce a new media access control (MAC) spoofing attack scenario injecting artificial noise, where the prediction accuracy of Wi-Fi-based indoor localization system significantly decreases. We also propose a new deep learning-based indoor localization method using random forest(RF)-filter to provide the good prediction accuracy under the new MAC spoofing attack scenario. From the experimental results, we show that the proposed indoor localization method provides much higher prediction accuracy than the previous methods in environments with artificial noise.

Incidence, Burden, and Predictors of 11-Month Readmission in Patients Undergoing Bariatric Surgery.

BACKGROUND: Bariatric surgery (BSx) is one of the most common surgical procedures performed in the USA. Nonetheless, data regarding 11-month period after BSx remain limited. METHODS: A retrospective cohort study using the 2016 National Readmission Database. Adult patients admitted for BSx in January were included. The follow-up period was 11 months (February-December). The primary outcome was all-cause 11-month readmission. Secondary outcomes were index admission (IA) and readmission in-hospital mortality rate and healthcare resource use associated with readmission. Multivariate regression was performed to identify independent risk factors for readmission. RESULTS: A total of 13,278 IA were included. The 11-month readmission rate was 11.1%. The mortality rate of readmission was 1.4% and 0.1% for IA (P < 0.01). The most common cause of readmission was hematemesis. Independent predictors were Charlson comorbidity index (CCI) score ≥ 3 (adjusted hazard ratio [aHR] 1.34; P = 0.05), increasing length of stay (aHR 1.01; P < 0.01), transfer to rehabilitation facilities (aHR 5.02; P < 0.01), undergoing laparoscopic Roux-en-Y gastric bypass (aHR 1.71; P = 0.02), adjustable gastric band (aHR 14.09; P < 0.01), alcohol use disorder (2.10; P = 0.01), and cannabis use disorder (aHR 3.37; P = 0.01). Private insurance as primary payer (aHR 0.65; P < 0.01) and BMI 45-49 kg/m2 (aHR 0.72; P < 0.01) were associated with less odds of readmission. The cumulative total hospitalization charges of readmission were $69.9 million. CONCLUSIONS: The 11-month readmission rate after BSx is 11.1%. Targeting modifiable predictors of readmission may help reduce the burden of readmissions on our healthcare system.

Modified Bedside Index for severity in acute pancreatitis (BISAP) score validation in the national inpatient sample database.

PURPOSE: The aim of this study was to build and validate modified score to be used in the healthcare cost and utilization project databases for further classification of acute pancreatitis (AP). MATERIALS AND METHODS: The National Inpatient Sample database for the years 2016-2019 was queried for all primary adult discharge diagnoses of AP. An mBISAP score system was created utilizing the ICD-10CM codes for pleural effusion, encephalopathy, acute kidney injury, systemic inflammatory response, and age >60. Each was assigned a 1-point score. A multivariable regression analysis was built to test for mortality. Sensitivity and specificity analyses were performed for mortality. RESULTS: A total of 1,160,869 primary discharges for AP were identified between 2016 and 2019. The pooled mortality rate was: 0.1%, 0.5%, 2.9%, 12.7%, 30.9% and 17.8% (P â€‹< â€‹0.01), respectively for scores 0 to 5. Multivariable regression analysis showed increasing odds of mortality with each one-point increment: mBISAP score of 1 (adjusted odds ratio [aOR] 6.67; 95% confidence interval [CI] 4.69-9.48), score of 2 (aOR 37.87; 95% CI 26.05- 55.03), score of 3 (aOR 189.38; 95% CI 127.47-281.38), score of 4 (aOR 535.38; 95% CI 331.74-864.02), score of 5 (aOR 184.38; 95% CI 53.91-630.60). Using a cut-off of ≥3, sensitivity and specificity analyses reported 27.0% and 97.7%, respectively, with an area under the curve (AUC) of 0.811. CONCLUSION: In this 4-year retrospective study of a US representative database, an mBISAP score was constructed showing increasing odds of mortality with each 1-point increase and a specificity of 97.7% for a cut-off of ≥3.

Photopolymerization-Based Synthesis of Uniform Magnetic Hydrogels and Colorimetric Glucose Detection.

Magnetic hydrogels have been commonly used in biomedical applications. As magnetite nanoparticles (MNPs) exhibit peroxidase enzyme-like activity, magnetic hydrogels have been actively used as signal transducers for biomedical assays. Droplet microfluidics, which uses photoinitiated polymerization, is a preferred method for the synthesis of magnetic hydrogels. However, light absorption by MNPs makes it difficult to obtain fully polymerized and homogeneous magnetic hydrogels through photoinitiated polymerization. Several methods have been reported to address this issue, but few studies have focused on investigating the light absorption properties of photoinitiators. In this study, we developed a simple method for the synthesis of poly(ethylene glycol) (PEG)-based uniform magnetic hydrogels that exploits the high ultraviolet absorption of a photoinitiator. Additionally, we investigated this effect on shape deformation and structural uniformity of the synthesized magnetic hydrogels. Two different photoinitiators, Darocur 1173 and lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP), with significantly different UV absorption properties were evaluated based on the synthesis of magnetic hydrogels. The magnetic characteristics of the PEG-stabilized MNPs in hydrogels were investigated with a vibrating sample magnetometer. Finally, the colorimetric detection of hydrogen peroxide and glucose was conducted based on the enzyme-like property of MNPs and repeated several times to observe the catalytic activity of the magnetic hydrogels.

Direct Evidence of Ion-Migration-Induced Degradation of Ultrabright Perovskite Light-Emitting Diodes.

Low operational lifetime is a critical issue in perovskite light-emitting diodes. The forward-bias currents for light emission accelerate device degradation, which needs to be identified and understood to be able to improve the device stability. Here, we systematically analyze the degradation mechanism of perovskite light-emitting diodes (PeLEDs) fabricated with a sequential deposition method that produce a compact and pinhole-free perovskite film. The device exhibits an efficient green electroluminescence (peak wavelength at 533 nm and full width at half-maximum of 22 nm) with a maximum luminance of more than 67 000 cd/m2. The lifetime, however, is quite short; under the constant current bias for an initial luminance of 1000 cd/m2, the decay time to reach half of the initial luminance is approximately 13 min. Dark spots are created and enlarged as a result of perovskite film deterioration and ion migration. By investigating morphological changes in the perovskite films and the amount of ion accumulation under the Al electrode for the unoperated, T50 (luminance decay to 50% of the initial value), and T10 (luminance decay to 10% of the initial value) devices, we propose a degradation mechanism for PeLEDs. The ion migration from the perovskite layer experienced electrochemical interactions with the Al electrode, causing device degradation.

Endoplasmic reticulum-associated degradation potentiates the infectivity of influenza A virus by regulating the host redox state.

During influenza A virus (IAV) infection, significant effects of oxidative stress often emerge due to the disruption of the redox balance. Reactive oxygen species (ROS) generated during IAV infection have been known to exert various effects on both the virus and host tissue. However, the mechanisms underlying the accumulation of ROS and their physiological significance in IAV infection have been extensively studied but remain to be fully understood. Here, we show that the levels of Sp1, a key controller of Cu-Zn superoxide dismutase (SOD1) gene expression, and SOD1 are mainly dependent upon the activity of X-box-binding protein 1 (XBP1), which is a downstream factor of the endoplasmic reticulum (ER) transmembrane sensor inositol-requiring enzyme 1 (IRE1) during ER stress. In IRE1-deficient mouse embryo fibroblasts (MEFs) or A549 human lung cells treated with XBP1 siRNA, IAV-induced Sp1 loss was mitigated. However, overexpression of the spliced form of XBP1 in IRE1-deficient MEFs resulted in a further decrease in Sp1 levels, whereas the unspliced form showed no significant differences. Treatment with proteasome inhibitor MG132 markedly inhibited the IRE1/XBP1-mediated loss of Sp1 and SOD, suggesting the involvement of proteasome-dependent ER-associated degradation (ERAD). The increase in SOD1 levels with the expression of siRNA-targeting p97, a central component of the ubiquitin-proteasome system, supports the major role of the ERAD process in IAV-mediated SOD1 loss. In addition, ROS generation due to IAV infection was attenuated in cells lacking either IRE1 or JNK. These results reveal the important roles of both IRE1/XBP1-mediated ERAD and the JNK pathway in IAV infection. Interestingly, the increase in ROS due to IAV infection is correlated with the increase in the virus titer in vitro and in vivo. However, 4-phenylbutyrate (4-PBA), an inhibitor of ER stress signaling, weakened the effect of IAV infection on SOD1 loss in a dose-dependent manner. Furthermore, the treatment of mice with 4-PBA efficiently attenuated ROS generation and ER stress in lung tissue and eventually lowered the IAV titer. These results strongly suggest that the ERAD process plays a major role in IAV infection, thus making it a potential target for antiviral drug therapy.

Synthesis of mesoporous lanthanum hydroxide with enhanced adsorption performance for phosphate removal.

Phosphate is a ubiquitous pollutant in aquatic systems, and increasingly stringent post-treatment phosphate effluent standards necessitate increasingly efficient removal techniques. In this study, mesoporous lanthanum hydroxide (MLHO) was synthesized by a hard-template method using ordered mesoporous silica, and its potential as an adsorbent for high-efficiency phosphate removal in aqueous solutions was tested. The porosity characteristics of MLHOs were controlled by adjusting the template structure and synthesis conditions. MLHO adsorbents showed great potential for phosphate removal from solutions containing both high and low initial phosphate concentrations. The phosphate adsorption capacity of MLHO strongly depended on its surface area as this process was governed by monolayer adsorption. Moreover, the phosphate removal performance of MLHO was affected by its structural properties. MLHO showed a high adsorption capacity of 109.41 mg P g-1 at 28 °C (q m by the Langmuir isotherm model). Further, it showed ultrafast adsorption in a solution with low initial concentration of 2 mg P/L; within the first 10 min, 99.8% of phosphate was removed, and the phosphorus concentration remaining in the solution dramatically reduced to 4 µg P/L. These findings suggest that MLHO adsorbent is a good candidate for rapid and efficient low-concentration phosphate removal to meet the increasingly stringent discharge standards for wastewater treatment plants.

Enantioselective additions of diethylzinc and diphenylzinc to aldehydes using 2-dialkyl-aminomethyl-2'-hydroxy- 1,1'-binaphthyls.

[reaction: see text] A set of 2-dialkylaminomethyl-2'-hydroxy-1,1'-binaphthyls was prepared and used in the catalytic asymmetric additions of diethylzinc and diphenylzinc to various types of aldehydes. These binaphthyl-based axially chiral amino alcohols show high enantioselectivity in the addition of organozincs to aromatic and aliphatic aldehydes.

Highly enantioselective additions of diethylzinc to aldehydes using 2-triflamido-methyl-2'-hydroxy-1,1'- binaphthyl.

[reaction: see text] A new N-triflated amino alcohol-titanium catalyst was designed for the asymmetric ethylation of aldehydes. This binaphthyl-based sulfonamido alcohol ligand shows uniformly high yield and enantioselectivity in the diethylzinc additions of aromatic, aliphatic, and unsaturated aldehydes.