Modeling the Effects of Hyaluronic Acid Degradation on the Regulation of Human Astrocyte Phenotype Using Multicomponent Interpenetrating Polymer Networks (mIPNs)

Hyaluronic acid (HA) is a highly abundant component in the extracellular matrix (ECM) and a fundamental element to the architecture and the physiology of the central nervous system (CNS). Often, HA degradation occurs when an overreactive inflammatory response, derived from tissue trauma or neurodegenerative diseases such as Alzheimer’s, causes the ECM in the CNS to be remodeled. Herein, we studied the effects of HA content as a key regulator of human astrocyte (HAf) reactivity using multicomponent interpenetrating polymer networks (mIPNs) comprised of Collagen I, HA and poly(ethylene glycol) diacrylate. The selected platform facilities the modulation of HA levels independently of matrix rigidity. Total astrocytic processes length, number of endpoints, the expression of the quiescent markers: Aldehyde Dehydrogenase 1 Family Member L1 (ALDH1L1) and Glutamate Aspartate Transporter (GLAST); the reactive markers: Glial Fibrillary Acidic Protein (GFAP) and S100 Calcium-Binding Protein β (S100β); and the inflammatory markers: Inducible Nitric Oxide Synthase (iNOS), Interleukin 1β (IL-1β) and Tumor Necrosis Factor Alpha (TNFα), were assessed. Cumulatively, our results demonstrated that the decrease in HA concentration elicited a reduction in the total length of astrocytic processes and an increase in the expression of HAf reactive and inflammatory markers

Collagen Based Multicomponent Interpenetrating Networks as Promising Scaffolds for 3D Culture of Human Neural Stem Cells, Human Astrocytes, and Human Microglia

This work describes for the first time the fabrication and characterization of multicomponent interpenetrating networks composed of collagen I, hyaluronic acid, and poly(ethylene glycol) diacrylate for the 3D culture of human neural stem cells, astrocytes, and microglia. The chemical composition of the scaffolds can be modulated while maintaining values of complex moduli within the range of the mechanical performance of brain tissue (∼6.9 kPa) and having cell viability exceeding 84%. The developed scaffolds are a promising new family of biomaterials that can potentially serve as 3D in vitro models for studying the physiology and physiopathology of the central nervous system

The Incidence and Incubation Period of False Positive Cultures in Shoulder Surgery

Background Postoperative shoulder infection (PSI) is a significant complication requiring timely identification and treatment. Indolent infections such as those involving Cutibacterium acnes (C. acnes, recently reclassified from Propionibacterium acnes 1) provide a diagnostic dilemma as they present differently without the acute symptoms associated with most postoperative bone and joint infections. Furthermore, C. acnes is thought to be a common contaminant isolated from intraoperative cultures. With no consensus algorithm, long hold cultures play a major role in guiding management decisions in potential PSI. Our study seeks to determine the incidence of positive cultures in both open and arthroscopic procedures in non-infected patients as well as clarify whether or not an increase in the incubation time frame leads to an increased rate of culture growth. Method ology: One hundred patients were prospectively enrolled into either an open and arthroscopic procedure group. Patients with abnormal inflammatory labs, history of previous shoulder surgery, or corticosteroid injection within six months of surgery were excluded from the study. Three cultures were obtained for each patient (1superficial tissue culture, 2- tissue culture, and 3- “sterile” control swab). Cultures were held for 28 days and checked on regular intervals. All patients were followed clinically for 6 months to ensure no signs of postoperative infection. Results Ultimately ninety-five patients were included in the final analysis. The false-positive rate in open shoulder surgery was 17.02% and arthroscopic shoulder surgery was 10.4%. The incidence of positive C. acnes cultures was 6.4% in the open group while C. acnes was not isolated in the arthroscopic group. All positive bacterial cultures were reported within seven days of collection. One culture was positive for “mold” at 26 days. Conclusion A relatively high false-positive culture rate occurred in both open and arthroscopic shoulder surgery. C. acnes was the most commonly identified bacteria in cultures in the open surgery group. Knowledge of one’s own institutional false-positive culture rate could be important in avoiding potentially inappropriate treatment. Additionally, we found that holding cultures longer than 14 days did not lead to an increased rate of false positive culture results

Air Data Boom System Development for the Max Launch Abort System (MLAS) Flight Experiment

In 2007, the NASA Exploration Systems Mission Directorate (ESMD) chartered the NASA Engineering Safety Center (NESC) to demonstrate an alternate launch abort concept as risk mitigation for the Orion project's baseline "tower" design. On July 8, 2009, a full scale and passively, aerodynamically stabilized MLAS launch abort demonstrator was successfully launched from Wallops Flight Facility following nearly two years of development work on the launch abort concept: from a napkin sketch to a flight demonstration of the full-scale flight test vehicle. The MLAS flight test vehicle was instrumented with a suite of aerodynamic sensors. The purpose was to obtain sufficient data to demonstrate that the vehicle demonstrated the behavior predicted by Computational Fluid Dynamics (CFD) analysis and wind tunnel testing. This paper describes development of the Air Data Boom (ADB) component of the aerodynamic sensor suite

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council