Dairy-inspired coatings for bone implants from whey protein isolate-derived self-assembled fibrils

To improve integration of a biomaterial with surrounding tissue, its surface properties may be modified by adsorption of biomacromolecules, e.g. fibrils. Whey protein isolate (WPI), a dairy industry by-product, supports osteoblastic cell growth. WPI’s main component, β-lactoglobulin, forms fibrils in acidic solutions. In this study, aiming to develop coatings for biomaterials for bone contact, substrates were coated with WPI fibrils obtained at pH 2 or 3.5. Importantly, WPI fibrils coatings withstood autoclave sterilization and appeared to promote human bone marrow stromal cells (hBMSC) spreading and differentiation. In the future, WPI fibrils coatings could facilitate immobilization of biomolecules with growth stimulating or antimicrobial propertie

Enhanced Bioactivity of Tailor-Made Glycolipid Enriched Manuka Honey

Glycolipids can be synthetized in deep eutectic solvents (DESs) as they possess low water content allowing a reversed lipase activity and thus enables ester formation. Based on this principle, honey can also serve as a media for glycolipid synthesis. Indeed, this supersaturated sugar solution is comparable in terms of physicochemical properties to the sugar-based DESs. Honey-based products being commercially available for therapeutic applications, it appears interesting to enhance its bioactivity. In the current work, we investigate if enriching medical grade honey with in situ enzymatically-synthetized glycolipids can improve the antimicrobial property of the mixture. The tested mixtures are composed of Manuka honey that is enriched with octanoate, decanoate, laurate, and myristate sugar esters, respectively dubbed GOH, GDH, GLH, and GMH. To characterize the bioactivity of those mixtures, first a qualitative screening using an agar well diffusion assay has been performed with methicillin-resistant Staphylococcus aureus, Bacillus subtilis, Candida bombicola, Escherichia coli, and Pseudomonas putida which confirmed considerably enhanced susceptibility of these micro-organisms to the different glycolipid enriched honey mixtures. Then, a designed biosensor E. coli strain that displays a stress reporter system consisting of three stress-specific inducible, red, green, and blue fluorescent proteins which respectively translate to physiological stress, genotoxicity, and cytotoxicity was used. Bioactivity was, therefore, characterized, and a six-fold enhancement of the physiological stress that was caused by GOH compared to regular Manuka honey at a 1.6% (v/v) concentration was observed. An antibacterial agar well diffusion assay with E. coli was performed as well and demonstrated an improved inhibitory potential with GOH upon 20% (v/v) concentration

Economic aspects of delivering primary care services: an evidence synthesis to inform policy and research priorities

Policy Points The 2018 Declaration of Astana reemphasized the importance of primary health care and its role in achieving universal health coverage. While there is a large amount of literature on the economic aspects of delivering primary care services, there is a need for more comprehensive overviews of this evidence. In this article, we offer such an overview. Evidence suggests that there are several strategies involving coverage, financing, service delivery, and governance arrangements which can, if implemented, have positive economic impacts on the delivery of primary care services. These include arrangements such as worker task-shifting and telemedicine. The implementation of any such arrangements, based on positive economic evidence, should carefully account for potential impacts on overall health care access and quality. There are many opportunities for further research, with notable gaps in evidence on the impacts of increasing primary care funding or the overall supply of primary care services. Context: The 2018 Declaration of Astana reemphasized the importance of primary health care and its role in achieving universal health coverage. To strengthen primary health care, policymakers need guidance on how to allocate resources in a manner that maximizes its economic benefits. Methods: We collated and synthesized published systematic reviews of evidence on the economic aspects of different models of delivering primary care services. Building on previous efforts, we adapted existing taxonomies of primary care components to classify our results according to four categories: coverage, financing, service delivery, and governance. Findings: We identified and classified 109 reviews that met our inclusion criteria according to our taxonomy of primary care components: coverage, financing, service delivery, and governance arrangements. A significant body of evidence suggests that several specific primary care arrangements, such as health workers' task shifting and telemedicine, can have positive economic impacts (such as lower overall health care costs). Notably absent were reviews on the impact of increasing primary care funding or the overall supply of primary care services. Conclusions: There is a great opportunity for further research to systematically examine the broader economic impacts of investing in primary care services. Despite progress over the last decade, significant evidence gaps on the economic implications of different models of primary care services remain, which could help inform the basis of future research efforts

Spectroscopic studies reveal details of substrate-induced conformational changes distant from the active site in isopenicillin N synthase

Isopenicillin N synthase (IPNS) catalyzes formation of the β-lactam and thiazolidine rings of isopenicillin N from its linear tripeptide l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) substrate in an iron- and dioxygen (O2)-dependent four-electron oxidation without precedent in current synthetic chemistry. Recent X-ray free-electron laser studies including time-resolved serial femtosecond crystallography show that binding of O2 to the IPNS–Fe(II)–ACV complex induces unexpected conformational changes in α-helices on the surface of IPNS, in particular in α3 and α10. However, how substrate binding leads to conformational changes away from the active site is unknown. Here, using detailed 19F NMR and electron paramagnetic resonance experiments with labeled IPNS variants, we investigated motions in α3 and α10 induced by binding of ferrous iron, ACV, and the O2 analog nitric oxide, using the less mobile α6 for comparison. 19F NMR studies were carried out on singly and doubly labeled α3, α6, and α10 variants at different temperatures. In addition, double electron–electron resonance electron paramagnetic resonance analysis was carried out on doubly spin-labeled variants. The combined spectroscopic and crystallographic results reveal that substantial conformational changes in regions of IPNS including α3 and α10 are induced by binding of ACV and nitric oxide. Since IPNS is a member of the structural superfamily of 2-oxoglutarate-dependent oxygenases and related enzymes, related conformational changes may be of general importance in nonheme oxygenase catalysis

Filaggrin gene defects are associated with eczema, wheeze, and nasal disease during infancy:Prospective study

This prospective cohort study describes associations between the presence of filaggrin gene mutations and eczema, rhinitis and wheeze from as early as age six months, raising new questions regarding underlying mechanisms and timing of interventions

Persistent Reductions in OCS Use in Patients With Severe, OCS-Dependent Asthma Treated With Dupilumab : LIBERTY ASTHMA TRAVERSE Study

Acknowledgments and funding sources Data first presented at the 118th International Conference of the American Thoracic Society (ATS 2022); San Francisco, CA, USA; May 13–18, 2022. Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02528214 (VENTURE)/NCT02134028 (TRAVERSE). Medical writing/editorial assistance was provided by Anthony Aggidis, PhD, of Excerpta Medica, and was funded by Sanofi and Regeneron Pharmaceuticals, Inc., according to the Good Publication Practice guideline. Alternate presenters: Anne Atenhan and Mayank Thakur.Peer reviewe

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. This post hoc analysis assesses the impact of OCS dose at baseline (≤10 o

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

FUNDING Regeneron Pharmaceuticals NCT0213402; NCT02528214 Sanofi NCT0213402; NCT02528214Peer reviewedPublisher PD

Dupilumab reduces OCS use and improves lung function in patients with severe OCS-dependent asthma

Peer reviewedPostprin