Intermittent Fasting Reduces Neuroinflammation and Cognitive Impairment in High-Fat Diet-Fed Mice by Downregulating Lipocalin-2 and Galectin-3.

Intermittent fasting (IF), an alternating pattern of dietary restriction, reduces obesity-induced insulin resistance and inflammation. However, the crosstalk between adipose tissue and the hippocampus in diabetic encephalopathy is not fully understood. Here, we investigated the protective effects of IF against neuroinflammation and cognitive impairment in high-fat diet(HFD)-fed mice. Histological analysis revealed that IF reduced crown-like structures and adipocyte apoptosis in the adipose tissue of HFD mice. In addition to circulating lipocalin-2 (LCN2) and galectin-3 (GAL3) levels, IF reduced HFD-induced increases in LCN2- and GAL3-positive macrophages in adipose tissue. IF also improved HFD-induced memory deficits by inhibiting blood-brain barrier breakdown and neuroinflammation. Furthermore, immunofluorescence showed that IF reduced HFD-induced astrocytic LCN2 and microglial GAL3 protein expression in the hippocampus of HFD mice. These findings indicate that HFD-induced adipocyte apoptosis and macrophage infiltration may play a critical role in glial activation and that IF reduces neuroinflammation and cognitive impairment by protecting against blood-brain barrier leakage.

Outsourcing facilities and their place in the U.S. drug supply chain.

The purpose of this commentary is to describe the ideal role of 503B outsourcing facilities in the U.S. drug supply chain. We also address the challenges that 503B outsourcing facilities are facing that limit their utilization and offer possible solutions. Section 503B outsourcing facilities are emerging contributors in compounding owing to their ability to compound large quantities of medication without requiring patient-specific prescriptions. As such, they play a valuable role in the U.S. drug supply chain. The use of outsourcing facilities to compound ready-to-use drug products is gaining traction in hospitals and other health care systems. Outsourcing facilities help hospitals that are facing time and cost constraints owing to the evolving regulatory landscape around compounding. Although outsourcing facilities are assets to the drug supply chain, there are several challenges to their use. The lack of a finalized 503B Bulks List has led to outsourcing facilities being overly cautious in compounding products using bulk drug substances. In addition, the time between Food and Drug Administration (FDA) inspections is undefined, and a lack of follow-up information regarding concerns identified during an inspection may result in uncertainties about the current state of the outsourcing facility. Health care providers, outsourcing facilities, and FDA need to work together to ensure that patients are provided the drugs they need in a safe and effective way.

Author Correction: Freeform micropatterning of living cells into cell culture medium using direct inkjet printing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Immobilization of planktonic algal spores by inkjet printing.

The algal cell immobilization is a commonly used technique for treatment of waste water, production of useful metabolites and management of stock culture. However, control over the size of immobilized droplets, the population of microbes, and production rate in current techniques need to be improved. Here, we use drop-on-demand inkjet printing to immobilize spores of the alga Ecklonia cava within alginate microparticles for the first time. Microparticles with immobilized spores were generated by printing alginate-spore suspensions into a calcium chloride solution. We demonstrate that the inkjet technique can control the number of spores in an ejected droplet in the range of 0.23 to 1.87 by varying spore densities in bioink. After the printing-based spore encapsulation, we observe initial sprouting and continuous growth of thallus until 45 days of culture. Our study suggest that inkjet printing has a great potential to immobilize algae, and that the ability to control the number of encapsulated spores and their microenvironments can facilitate research into microscopic interactions of encapsulated spores.

Inkjet-Spray Hybrid Printing for 3D Freeform Fabrication of Multilayered Hydrogel Structures.

Here, a new bioprinting process by combining drop-on-demand inkjet printing with a spray-coating technique, which enables the high-resolution, high-speed, and freeform fabrication of large-scale cell-laden hydrogel structures is reported. Hydrogel structures with various shapes and composed of different materials, including alginate, cellulose nanofiber, and fibrinogen, are fabricated using the inkjet-spray printing. To manufacture cell-friendly hydrogel structures with controllable stiffness, gelatine methacryloyl is saponified to stabilize jet formation and is subsequently mixed with sodium alginate to prepare blend inks. The hydrogels crosslinked from the blend inks are characterized by assessing physical properties including the microstructure and mechanical stiffness and cellular responses including the cell viability, metabolic activity, and functionality of human dermal fibroblasts within the hydrogel. Cell-laden hydrogel structures are generated on a large scale and collagen type I secretion and spreading of cells within the hydrogels are assessed. The results demonstrate that the inkjet-spray printing system will ensure the formation of a cell-laden hydrogel structure with high shape fidelity in a rapid and reliable manner. Ultimately, the proposed printing technique and the blend bioink to be used to fabricate 3D laminated large-scale tissue equivalents that potentially mimic the function of native tissues is expected.

The Cost of Self-Reported Penicillin Allergy: A Systematic Review.

BACKGROUND: Patients who report a penicillin (PCN) allergy receive suboptimal antibiotic therapy compared with patients not reporting an allergy. However, a majority of patients who report PCN allergy are not truly allergic on confirmatory testing. Ruling out PCN allergy by testing may improve clinical and economic outcomes for patients with reported allergies requiring antibiotic therapy. OBJECTIVE: The objective of this study was to summarize clinical and economic outcomes associated with PCN allergy and provide recommendations for future cost-effectiveness analyses for PCN allergy testing. METHODS: A literature search was conducted using SCOPUS, EMBASE, and PubMed, including all articles published any date through April 25, 2017 (PROSPERO Registration number 42017064112). A total of 1518 abstracts were found during the initial search with 96 duplicates, for a total of 1422 articles for screening. Thirty articles were included for qualitative synthesis and full data extraction. RESULTS: The majority of the studies included had an observational design focusing on inpatient admissions. The most frequently measured outcome in the context of PCN allergy was optimizing antibiotic therapy. Patients with PCN allergy were found to have direct drug costs during inpatient admission ranging from no difference to an additional $609/patient compared with patients without PCN allergy. Outpatient prescription costs were estimated from $14 to $193/patient higher for PCN allergic patients. Total inpatient costs were less for patients without PCN allergy with average savings from $1145 to $4254/patient. CONCLUSIONS: Evaluations of clinical and economic outcomes of PCN allergy are primarily observational and focus on inpatient populations. Long-term relationships between PCN allergy and clinical and economic outcomes are unknown.

Publisher Correction: Freeform micropatterning of living cells into cell culture medium using direct inkjet printing.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Freeform micropatterning of living cells into cell culture medium using direct inkjet printing.

Microfabrication methods have widely been used to control the local cellular environment on a micron scale. However, accurately mimicking the complexity of the in vivo tissue architecture while maintaining the freedom of form and design is still a challenge when co-culturing multiple types of cells on the same substrate. For the first time, we present a drop-on-demand inkjet printing method to directly pattern living cells into a cell-friendly liquid environment. High-resolution control of cell location is achieved by precisely optimizing printing parameters with high-speed imaging of cell jetting and impacting behaviors. We demonstrated the capabilities of the direct cell printing method by co-printing different cells into various designs, including complex gradient arrangements. Finally, we applied this technique to investigate the influence of the heterogeneity and geometry of the cell population on the infectivity of seasonal H1N1 influenza virus (PR8) by generating A549 and HeLa cells printed in checkboard patterns of different sizes in a medium-filled culture dish. Direct inkjet cell patterning can be a powerful and versatile tool for both fundamental biology and applied biotechnology.