Subconjunctival delivery of p75NTR antagonists reduces the inflammatory, vascular, and neurodegenerative pathologies of diabetic retinopathy

The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections. METHODS. We compared the pharmacokinetics of a single 40 lg subconjunctival (SCJ) depot to the reported effective 5 lg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death. RESULTS. The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure. CONCLUSIONS. Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.Fil: Galan, Alba. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Barcelona, Pablo Federico. Mc Gill University. Lady Davis Research Intitute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nedev, Hinyu. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Sarunic, Marinko V.. University Fraser Simon; CanadáFil: Jian, Yifan. University Fraser Simon; CanadáFil: Saragovi, H. Uri. Mc Gill University. Lady Davis Research Intitute; Canad

Pneumonia Detection on Chest X-ray using Radiomic Features and Contrastive Learning

Chest X-ray becomes one of the most common medical diagnoses due to its noninvasiveness. The number of chest X-ray images has skyrocketed, but reading chest X-rays still have been manually performed by radiologists, which creates huge burnouts and delays. Traditionally, radiomics, as a subfield of radiology that can extract a large number of quantitative features from medical images, demonstrates its potential to facilitate medical imaging diagnosis before the deep learning era. With the rise of deep learning, the explainability of deep neural networks on chest X-ray diagnosis remains opaque. In this study, we proposed a novel framework that leverages radiomics features and contrastive learning to detect pneumonia in chest X-ray. Experiments on the RSNA Pneumonia Detection Challenge dataset show that our model achieves superior results to several state-of-the-art models (> 10% in F1-score) and increases the model's interpretability.Comment: Accepted for ISBI 202

Measuring psi(3770) -> Kshort Klong as a test of the S- and D-wave mixing of charmonia

Adding to the long standing "rho-pi puzzle" in psi(3686) and J/psi decays, recently BES reported the branching ratio of psi(3686) -> Kshort Klong which is enhanced relative to the pQCD " 12% rule" expectation from the branching ratio of J/psi -> Kshort Klong. If the enhancement is due to the mixing of the S- and D-wave charmonium states as in the rho-pi case, the newly measured branching ratio of psi(3686) -> Kshort Klong gives a constraint on the psi(3770) -> Kshort Klong. It serves as a good test for the scenario of the S- and D-wave mixing in the psi(3686) and psi(3770).Comment: 4 pages, 1 figur

Tensile behaviour of pitting corroded steel bars:Laboratory investigation and probabilistic-based analysis

Localised corrosion in steel bars has been a long-standing issue in the durability of reinforced concrete structures, but a comprehensive scheme for the analysis of pitting corroded steel bars, especially with respect to the deformation capacity, is not currently available. In this study, the morphological characteristics of 27 pitting steel bars were captured using a 3D scanner. The measured data were used to establish the probability distribution model of the cross-sectional areas of the corroded bars. Uniaxial tensile tests were conducted, and the evolving deformation field of the corroded bars was recorded through Digital Image Correlation (DIC). Based on the 3D reconstructed model and DIC results, an analytical method for evaluating the mechanical properties of pitting steel bars was developed and validated. The results show that the two-component Gaussian mixture distribution model outperforms conventional unimodal distribution models. Comparison of the analytical results with experimental data demonstrates that the proposed procedure is capable of predicting not only the ultimate strength but also the gauge length-dependent ultimate strain of corroded bars. Additionally, there exists a strengthening effect in the ultimate stress at the critical sections and this effect should not be ignored for accurate predictions.</p

Impact of Outpatient vs Inpatient ABSSSI Treatment on Outcomes: A Retrospective Observational Analysis of Medical Charts Across US Emergency Departments

Background The objective of this study was to characterize treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) and describe the association between hospital admission and emergency department (ED) visits or readmissions within 30 days after initial episode of care (IEC). Methods This was a retrospective, observational, cohort study of adults with ABSSSI who presented to an ED between July 1, 2012, and June 30, 2013. Patient, health care facility, and treatment characteristics, including unplanned ED visits or readmissions, were obtained through manual chart review and abstraction. Adjusted logistic regression analysis examined likelihood of all-cause unplanned ED visits or readmissions between admitted and nonadmitted patients. Results Records from 1527 ED visits for ABSSSI from 40 centers were reviewed (admitted, n = 578 [38%]; nonadmitted, n = 949 [62%]). Admitted patients were typically older (mean age, 52.2 years vs 43.0 years), more likely to be morbidly obese (body mass index \u3e 40 kg/m2; 17.3% vs 9.1%), and had more comorbidities (Charlson Comorbidity Index ≥ 4; 24.4% vs 6.8%) compared with those not admitted. In the primary analysis, adjusted logistic regression, controlling for comorbidities and severity of illness, demonstrated that there was a similar likelihood of all-cause unplanned ED visits or readmissions between admitted and nonadmitted patients (odds ratio, 1.03; 95% confidence interval, 0.74–1.43; P = .87). Conclusions ABSSSI treatment pathways leveraging outpatient treatment vs hospital admission support similar likelihood of unplanned 30-day ED visits or readmissions, an important clinical outcome and quality metric at US hospitals. Further research regarding the decision criteria around hospital admission to avoid potentially unnecessary hospitalizations is warranted