[Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis].

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Self-Assembled Nanoparticles from Xie-Bai-San Decoction: Isolation, Characterization and Enhancing Oral Bioavailability.

Background: Natural nanoparticles have been found to exist in traditional Chinese medicine (TCM) decoctions. However, whether natural nanoparticles can influence the oral bioavailability of active compounds has not been elucidated. Using Xie-Bai-San decoction (XBSD) as an example, the purpose of this study was to isolate, characterize and elucidate the mechanism of the nanoparticles (N-XBSD) in XBSD, and further to explore whether the bioavailability of the main active compounds could be enhanced by N-XBSD. Methods: N-XBSD were isolated from XBSD, and investigated its characterization and study of its formation mechanism, and evaluation of its ability to enhance bioavailability of active compounds. Results: The N-XBSD was successfully isolated with the average particle size of 104.53 nm, PDI of 0.27 and zeta potential of -5.14 mV. Meanwhile, all the eight active compounds were most presented in N-XBSD. Kukoamine B could self-assemble with mulberroside A or liquiritin to form nanoparticles, respectively. And the FT-IR and HRMS results indicated the possible binding of the ammonium group of kukoamine B with the phenolic hydroxyl group of mulberroside A or liquiritin, respectively. The established UPLC-MS/MS method was accurate and reliable and met the quantitative requirements. The pharmacokinetic behaviors of the N-XBSD and decoction were similar in rats. Most notably, compared to that of free drugs, the Cmax, AUC0-∞, AUC0-t, T1/2 and MRT0-∞ values of index compounds were the higher in N-XBSD, with a slower plasma clearance rate in rats. Conclusion: The major active compounds of XBSD were mainly distributed in N-XBSD, and N-XBSD was formed through self-assembly among active compounds. N-XBSD could obviously promote the bioavailability of active compounds, indicating natural nanoparticles of decoctions play an important role in therapeutic effects.

High-level production of Rhodiola rosea characteristic component rosavin from D-glucose and L-arabinose in engineered Escherichia coli.

Rosavin is the characteristic component of Rhodiola rosea L., an important medicinal plant used widely in the world that has been reported to possess multiple biological activities. However, the endangered status of wild Rhodiola has limited the supply of rosavin. In this work, we successfully engineered an Escherichia coli strain to efficiently produce rosavin as an alternative production method. Firstly, cinnamate: CoA ligase from Hypericum calycinum, cinnamoyl-CoA reductase from Lolium perenne, and uridine diphosphate (UDP)-glycosyltransferase (UGT) from Bacillus subtilis (Bs-YjiC) were selected to improve the titer of rosin in E. coli. Subsequently, four UGTs from the UGT91R subfamily were identified to catalyze the formation of rosavin from rosin, with SlUGT91R1 from Solanum lycopersicum showing the highest activity level. Secondly, production of rosavin was achieved for the first time in E. coli by incorporating the SlUGT91R1 and UDP-arabinose pathway, including UDP-glucose dehydrogenase, UDP-xylose synthase, and UDP-xylose 4-epimerase, into the rosin-producing stain, and the titer reached 430.5 ± 91.4 mg/L. Thirdly, a two-step pathway derived from L-arabinose, composed of L-arabinokinase and UDP-sugar pyrophosphorylase, was developed in E. coli to further optimize the supply of the precursor UDP-arabinose. Furthermore, 1203.7 ± 32.1 mg/L of rosavin was produced from D-glucose and L-arabinose using shake-flask fermentation. Finally, the production of rosavin reached 7539.1 ± 228.7 mg/L by fed-batch fermentation in a 5-L bioreactor. Thus, the microbe-based production of rosavin shows great potential for commercialization. This work provides an effective strategy for the biosynthesis of other valuable natural products with arabinose-containing units from D-glucose and L-arabinose.

Effects of ferric derisomaltose on postoperative anaemia in adult spinal deformity surgery: a study protocol for a randomised controlled trial.

INTRODUCTION: Postoperative anaemia is prevalent in adult spinal deformity (ASD) surgery in association with unfavourable outcomes. Ferric derisomaltose, a novel iron supplement, offers a promising solution in rapidly treating postoperative anaemia. However, the clinical evidence of its effect on patients receiving spinal surgery remains inadequate. This randomised controlled trial aims to evaluate the safety and efficacy of ferric derisomaltose on postoperative anaemia in ASD patients. METHODS AND ANALYSIS: This single-centre, phase 4, randomised controlled trial will be conducted at Department of Orthopaedics at Peking Union Medical College Hospital and aims to recruit adult patients who received ASD surgery with postoperative anaemia. Eligible participants will be randomly assigned to receive ferric derisomaltose infusion or oral ferrous succinate. The primary outcome is the change in haemoglobin concentrations from postoperative days 1-14. Secondary outcomes include changes in iron parameters, reticulocyte parameters, postoperative complications, allogeneic red blood cell infusion rates, length of hospital stay, functional assessment and quality-of-life evaluation. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of Peking Union Medical College Hospital and registered at ClinicalTrials.gov. Informed consent will be obtained from all participants prior to enrolment and the study will be conducted in accordance with the principles of the Declaration of Helsinki. The results of this study are expected to be disseminated through peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT05714007.

Rosavin: Research Advances in Extraction and Synthesis, Pharmacological Activities and Therapeutic Effects on Diseases of the Characteristic Active Ingredients of Rhodiola rosea L.

Rhodiola rosea L. (RRL) is a popular plant in traditional medicine, and Rosavin, a characteristic ingredient of RRL, is considered one of the most important active ingredients in it. In recent years, with deepening research on its pharmacological actions, the clinical application value and demand for Rosavin have been steadily increasing. Various routes for the extraction and all-chemical or biological synthesis of Rosavin have been gradually developed for the large-scale production and broad application of Rosavin. Pharmacological studies have demonstrated that Rosavin has a variety of biological activities, including antioxidant, lipid-lowering, analgesic, antiradiation, antitumor and immunomodulation effects. Rosavin showed significant therapeutic effects on a range of chronic diseases, including neurological, digestive, respiratory and bone-related disorders during in vitro and vivo experiments, demonstrating the great potential of Rosavin as a therapeutic drug for diseases. This paper gives a comprehensive and insightful overview of Rosavin, focusing on its extraction and synthesis, pharmacological activities, progress in disease-treatment research and formulation studies, providing a reference for the production and preparation, further clinical research and applications of Rosavin in the future.

Irritable bowel syndrome and endometriosis: diagnosis, similarities, and nutritional management.

Irritable bowel syndrome (IBS) and endometriosis pose significant challenges to affected individuals. IBS, which is a functional gastrointestinal disorder, affects 5-10% of the population, while endometriosis affects 1 in 10 of those assigned female at birth. Despite distinct origins, symptom often overlap, which may lead to misdiagnosis. Diagnosing IBS and endometriosis requires a comprehensive approach. Nutritional management for IBS emphasises self-help strategies, nutritional changes and gut-brain axis modulation. The low FODMAP diet, which reduces the intake of foods containing specific types of carbohydrate, can be effective but requires the support of trained health professionals. For the management of endometriosis, a Mediterranean-style diet rich in antioxidants shows promise. Gastrointestinal symptoms are common with endometriosis and an individualised approach is recommended. Furthermore, vitamin D status assessment is advised. Collaboration between health professionals and dietitians is vital for tailored interventions, to enhance the wellbeing of individuals with IBS or endometriosis. A holistic approach holds promise in symptom management for both conditions.

Intravenous ferric carboxymaltose and ferric derisomaltose alter the intestinal microbiome in female iron-deficient anemic mice.

Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron stores, either by oral or intravenous (IV) supplementation. There is a complex bidirectional interplay between the gut microbiota, the host's iron status, and dietary iron availability. Dietary iron deficiency and supplementation can influence the gut microbiome; however, the effect of IV iron on the gut microbiome is unknown. We studied how commonly used IV iron preparations, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), affected the gut microbiome in female iron-deficient anemic mice. At the phylum level, vehicle-treated mice showed an expansion in Verrucomicrobia, mostly because of the increased abundance of Akkermansia muciniphila, along with contraction in Firmicutes, resulting in a lower Firmicutes/Bacteroidetes ratio (indicator of dysbiosis). Treatment with either FCM or FDI restored the microbiome such that Firmicutes and Bacteroidetes were the dominant phyla. Interestingly, the phyla Proteobacteria and several members of Bacteroidetes (e.g., Alistipes) were expanded in mice treated with FCM compared with those treated with FDI. In contrast, several Clostridia class members were expanded in mice treated with FDI compared with FCM (e.g., Dorea spp., Eubacterium). Our data demonstrate that IV iron increases gut microbiome diversity independently of the iron preparation used; however, differences exist between FCM and FDI treatments. In conclusion, replenishing iron stores with IV iron preparations in clinical conditions, such as inflammatory bowel disease or chronic kidney disease, could affect gut microbiome composition and consequently contribute to an altered disease outcome.

Systematic Analysis of Galactinol Synthase and Raffinose Synthase Gene Families in Potato and Their Expression Patterns in Development and Abiotic Stress Responses.

Raffinose family oligosaccharides (RFOs) are very important for plant growth, development, and abiotic stress tolerance. Galactinol synthase (GolS) and raffinose synthase (RFS) are critical enzymes involved in RFO biosynthesis. However, the whole-genome identification and stress responses of their coding genes in potato remain unexplored. In this study, four StGolS and nine StRFS genes were identified and classified into three and five subgroups, respectively. Remarkably, a total of two StGolS and four StRFS genes in potato were identified to form collinear pairs with those in both Arabidopsis and tomato, respectively. Subsequent analysis revealed that StGolS4 exhibited significantly high expression levels in transport-related tissues, PEG-6000, and ABA treatments, with remarkable upregulation under salt stress. Additionally, StRFS5 showed similar responses to StGolS4, but StRFS4 and StRFS8 gene expression increased significantly under salt treatment and decreased in PEG-6000 and ABA treatments. Overall, these results lay a foundation for further research on the functional characteristics and molecular mechanisms of these two gene families in response to ABA, salt, and drought stresses, and provide a theoretical foundation and new gene resources for the abiotic-stress-tolerant breeding of potato.

Celiac Disease: An Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guideline.

Celiac disease is an autoimmune disorder in which the immune system of genetically susceptible individuals elicits a reaction to gluten causing small intestine damage. If left undiagnosed and untreated, the resulting nutrition malabsorption can lead to anemia, bone disease, growth faltering, or other consequences. The condition is lifelong and lacks a cure; the only treatment is lifelong adherence to a gluten-free diet (GFD). This diet is challenging to follow and adversely influences quality of life; however, it is essential to ensure intestinal recovery and prevent future negative health consequences. The Academy of Nutrition and Dietetics convened an expert panel complemented by a celiac disease patient advocate to evaluate evidence for six topics, including medical nutrition therapy; the GFD; oat consumption; micronutrients; pro-/prebiotics; and the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet. This publication outlines the Academy of Nutrition and Dietetics Evidence Analysis Library methods used to complete the systematic review and guideline development, and summarizes the recommendations and supporting evidence. The guidelines affirm that all individuals with celiac disease should follow a GFD (1C, Imperative) that may include gluten-free oats in adults (2D, Conditional). Children should follow a nutritionally adequate GFD that supports healthy growth and development (Consensus, Imperative) and does not unnecessarily restrict gluten-free oats (Consensus, Conditional). The guidelines indicate nutritional care should include routine nutritional assessment (Consensus, Imperative) and medical nutrition therapy (Consensus, Imperative). At this time, the guidelines do not support a recommendation for the addition of the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (2C, Conditional); prebiotic or probiotic supplementation (2D, Conditional); or micronutrient supplementation (in the absence of nutritional deficiency) (Consensus, Conditional). The 2021 Celiac Disease Evidence-Based Nutrition Guideline will assist registered dietitian nutritionists in providing appropriate evidence-based medical nutrition therapy to support people with celiac disease in achieving and maintaining nutritional health and avoiding adverse celiac disease consequences throughout their lives.

Update on treatment of abdominal pain in irritable bowel syndrome: A narrative review.

The objectives of this narrative review are to update readers on the current state-of-the-art regarding diverse approaches for the treatment of pain, global symptoms, or adequate relief in irritable bowel syndrome (IBS). The article appraises medications, dietary interventions including low fermentable oligosaccharides, disaccharides, and monosaccharides and polyols (FODMAP) diet, fecal microbial transplantation (FMT), electrical approaches, and behavioral therapies including cognitive behavioral therapy (CBT), gut-directed hypnotherapy (GDH), mindfulness, and open-label placebo. Current evidence demonstrates only modest benefit in global IBS symptoms and pain relief. A future approach that identifies pathophysiological mechanisms of IBS through validated biomarkers has the potential to individualize treatment of patients rather than sequential therapeutic trial and error approaches.

Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from Swim Bladder: Isolation, Structural Analysis, and Anticoagulant Activity.

Glycosaminoglycans (GAGs) with unique structures from marine animals show intriguing pharmacological activities and negligible biological risks, providing more options for us to explore safer agents. The swim bladder is a tonic food and folk medicine, and its GAGs show good anticoagulant activity. In this study, two GAGs, CMG-1.0 and GMG-1.0, were extracted and isolated from the swim bladder of Cynoscion microlepidotus and Gadus morhua. The physicochemical properties, precise structural characteristics, and anticoagulant activities of these GAGs were determined for the first time. The analysis results of the CMG-1.0 and GMG-1.0 showed that they were chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains with molecular weights of 109.3 kDa and 123.1 kDa, respectively. They were mainly composed of the repeating disaccharide unit of -{IdoA-α1,3-GalNAc4S-ß1,4-}- (DS-A). The DS-B disaccharide unit of -{IdoA2S-α1,3-GalNAc4S-ß1,4-}- also existed in both CMG-1.0 and GMG-1.0. CMG-1.0 had a higher proportion of CS-O disaccharide unit -{-GlcA-ß1,3-GalNAc-ß1,4-}- but a lower proportion of CS-E disaccharide unit -{-GlcA-ß1,3-GalNAc4S6S-ß1,4-}- than GMG-1.0. The disaccharide compositions of the GAGs varied in a species-specific manner. Anticoagulant activity assay revealed that both CMG-1.0 and GMG-1.0 had potent anticoagulant activity, which can significantly prolong activated partial thromboplastin time. GMG-1.0 also can prolong the thrombin time. CMG-1.0 showed no intrinsic tenase inhibition activity, while GMG-1.0 can obviously inhibit intrinsic tenase with EC50 of 58 nM. Their significantly different anticoagulant activities may be due to their different disaccharide structural units and proportions. These findings suggested that swim bladder by-products of fish processing of these two marine organisms may be used as a source of anticoagulants.

Deaminative-cleaved S. monotuberculatus fucosylated glycosaminoglycan: Structural elucidation and anticoagulant activity.

Stichopus monotuberculatus is a tropical sea cucumber species and used as a folk medicine and tonic food. In this study, a fucosylated glycosaminoglycan (SmFG), the depolymerized SmFG (dSmFG) and its oligosaccharide fractions were prepared. The SmFG and its depolymerized products were comprised of a chondroitin-sulfate-E backbone, and various sulfated fucose side chains, including an unusual disaccharide side chain connected to the C-3 position of D-glucuronic acid (GlcA) or GlcA-ol. A peeling reaction occurred during the deaminative depolymerization process. The dSmFG and its fractions showed strong anticoagulant activity by selectively inhibiting intrinsic tenase complex, and had no anti-factor IIa, Xa and VIIa activity. The anticoagulant activity reduced with the decrease of molecular weight, and the unusual branch and novel reducing end may enhance the anticoagulant activity. These findings can provide significant information for development and utilization of depolymerized products from SmFG in food and pharmaceutical industries.

Accumulation of Galactinol and ABA Is Involved in Exogenous EBR-Induced Drought Tolerance in Tea Plants.

Drought stress severely limits growth and causes losses in the yield of tea plants. Exogenous application of 24-epibrassinolide (EBR) positively regulates drought responses in various plants. However, whether EBR could contribute to drought resistance in tea plants and the underlying mechanisms has not been investigated. Here, we found that EBR application is beneficial for the drought tolerance of tea plants. The transcriptome results revealed that EBR could contribute to tea plant drought resistance by promoting galactinol and abscisic acid (ABA) biosynthesis gene expression. The content of galactinol was elevated by EBR and EBR-responsive CsDof1.1 positively regulated the expression of the galactinol synthase genes CsGolS2-1 and CsGolS2-2 to contribute to the accumulation of galactinol by directly binding to their promoters. Moreover, exogenous EBR was found to elevate the expression of genes related to ABA signal transduction and stomatal closure regulation, which resulted in the promotion of stomatal closure. In addition, EBR-responsive CsMYC2-2 is involved in ABA accumulation by binding to the promoters CsNCED1 and CsNCED2 to activate their expression. In summary, findings in this study provide knowledge into the transcriptional regulatory mechanism of EBR-induced drought resistance in tea plants.

Boar semen cryopreserved with trehalose-containing liposomes: disaccharide determination and rheological behaviour.

This study aimed to detect intracellular trehalose in boar sperm that were cryopreserved with liposomes and conduct an analysis of its effects on some characteristics of thawed sperm, including rheological properties. First, soybean lecithin cholesterol-based liposomes were produced and characterized in the presence of 300 mM trehalose. Next, semen samples were frozen in two freezing media: a control medium with 300 mM trehalose and an experimental medium supplemented with 300 mM trehalose and 10% liposomes, both of which were thawed and then studied to ascertain their integrity, motility, rheological response, and trehalose quantities by testing two methods of spermatic lysis via high-performance liquid chromatography with an evaporative light-scattering detector (HPLC-ELSD). The results found spherical liposomes measuring 357 nm that were relatively stable in an aqueous medium and had an entrapment efficiency of 73%. An analysis of the cryopreserved ejaculates showed that their viability and motility did not significantly differ between groups (P > 0.05). The viscous response of the samples was influenced by the extracellular medium rather than by the freezing-thawing process, which resulted in a loss of interaction between the cells and cryoprotectants. Finally, intracellular trehalose levels were determined using HPLC-ELSD, with no differences observed (P > 0.05) when comparing both sperm lysis methods. The use of liposomes with trehalose appears to be a promising option for boar semen cryopreservation, with a marked effect on rheological properties. The proposed HPLC-ELSD method was effective for measuring trehalose in cryopreserved cell samples.

Effect of intraoperative intravenous ferric derisomaltose supplementation on reduction of postoperative anemia and transfusion in chronic kidney disease patients after total knee replacement.

Total knee replacement (TKR) is associated with a large amount of bleeding; therefore, the prevalence of postoperative anemia is high. In particular, patients with chronic kidney disease (CKD) are more vulnerable to postoperative anemia than are healthy individuals. Accordingly, the effect of intraoperative intravenous ferric derisomaltose (FDI) supplementation on postoperative anemia and blood transfusion volume reduction in patients with CKD was studied. Patients who underwent unilateral TKR between January 2019 and December 2020 were retrospectively reviewed. In analyzing the data, the patients fell into the CKD group (n = 85) and the non-CKD group (n = 106). Each group was divided into a group using FDI and a non-FDI group, and classified into 4 groups. The postoperative hemoglobin level for each postoperative day (POD) was determined as the primary outcome. In addition, the patient transfusion rate, volume of transfusion, and length of hospital stay were set as secondary study outcomes during the period from surgery to discharge. There was no statistically significant difference in hemoglobin levels on PODs 0, 1, 2, 7, and 14 in the CKD group. In the CKD group, the transfusion volume of the FDI group was 0.58 ± 0.91 units per person, which was statistically significantly lower than 1.28 ± 1.28 units of the non-FDI group (P = .01). In the CKD group, the transfusion rate of the FDI group was 30.2%, which was statistically significantly lower than that of the non-FDI group, which was 56.3% (P = .02). This study showed that intravenous FDI supplementation after TKR in CKD patients did not reduce postoperative anemia but was an effective and safe treatment to reduce transfusion volume and transfusion rate. There was no statistically significant difference in hemoglobin levels on POD 0, 1, 2, 7, and 14 in the non-CKD group. In the non-CKD group, the transfusion volume of the FDI group was 0.46 ± 0.88 units per person, which was lower than the 0.56 ± 0.91 units of the non-FDI group, but it was not statistically significant (P = .59). In the non-CKD group, the transfusion rate of the FDI group was 23.0%, which was lower than that of the non-FDI group, which was 31.3%, but it was not statistically significant (P = .37).

Efficacy of high-dose intravenous iron in middle-aged to elderly iron-deficient patients.

Iron deficiency (ID) impacts about fifty percent of elderly patients with many symptoms present before iron deficiency anaemia . If left untreated, ID may increase morbidity and mortality. Oral iron is often not tolerated or the absorption is suboptimal. We describe our initial experiences of using high-dose intravenous ferric derisomaltose (Monofer®) infusions of 500 and 1000mg for iron deficiency and iron deficiency anaemia respectively in the outpatient setting. Rapid correction of laboratory parameters and improvement in common symptoms (such as fatigue) were observed. Intravenous iron may be an option for symptomatic iron deficient patients unsuitable for oral iron.

High-Dose Intravenous Iron with Either Ferric Carboxymaltose or Ferric Derisomaltose: A Benefit-Risk Assessment.

The intravenous iron formulations ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) offer the possibility of administering a large amount of iron in one infusion. This results in faster correction of anemia and the formulations being better tolerated than oral iron formulations. This triad of logistic advantages, improved patient convenience, and fast correction of anemia explains the fact that intravenous iron formulations nowadays are frequently prescribed worldwide in the treatment of iron deficiency anemia. However, these formulations may result in hypophosphatemia by inducing a strong increase in active fibroblast growth factor-23 (FGF-23), a hormone that stimulates renal phosphate excretion. This effect is much more pronounced with FCM than with FDI, and therefore the risk of developing hypophosphatemia is remarkably higher with FCM than with FDI. Repeated use of FCM may result in severe osteomalacia, which is characterized by bone pain, Looser zones (pseudofractures), and low-trauma fractures. Intravenous iron preparations are also associated with other adverse effects, of which hypersensitivity reactions are the most important and are usually the result of a non-allergic complement activation on nanoparticles of free labile iron-Complement Activation-Related Pseudo-Allergy (CARPA). The risk on these hypersensitivity reactions can be reduced by choosing a slow infusion rate. Severe hypersensitivity reactions were reported in < 1% of prospective trials and the incidence seems comparable between the two formulations. A practical guideline has been developed based on baseline serum phosphate concentrations and predisposing risk factors, derived from published cases and risk factor analyses from trials, in order to establish the safe use of these formulations.

Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine.

Various chemical adjuvants are available to augment immune responses to non-replicative, subunit vaccines. Optimized adjuvant selection can ensure that vaccine-induced immune responses protect against the diversity of pathogen-associated infection routes, mechanisms of infectious spread, and pathways of immune evasion. In this study, we compare the immune response of mice to a subunit vaccine of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) spike protein, stabilized in its prefusion conformation by a proprietary molecular clamp (MERS SClamp) alone or formulated with one of six adjuvants: either (i) aluminium hydroxide, (ii) SWE, a squalene-in-water emulsion, (iii) SQ, a squalene-in-water emulsion containing QS21 saponin, (iv) SMQ, a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D-6-acyl Phosphorylated HexaAcyl Disaccharide (3D6AP); (v) LQ, neutral liposomes containing cholesterol, 1.2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and QS21, (vi) or LMQ, neutral liposomes containing cholesterol, DOPC, QS21, and 3D6AP. All adjuvanted formulations induced elevated antibody titers which where greatest for QS21-containing formulations. These had elevated neutralization capacity and induced higher frequencies of IFNƔ and IL-2-producing CD4+ and CD8+ T cells. Additionally, LMQ-containing formulations skewed the antibody response towards IgG2b/c isotypes, allowing for antibody-dependent cellular cytotoxicity. This study highlights the utility of side-by-side adjuvant comparisons in vaccine development.

Post-operative iron in cardiac surgery trial - a protocol for a randomised controlled trial.

INTRODUCTION: Anaemia is common after cardiac surgery and has a negative impact on rehabilitation and patient well-being. We aim to compare the efficacy of single, high-dose intravenous iron therapy versus oral iron supplementation to correct anaemia following open cardiac surgery. METHODS: We present a randomised, active-control superiority trial. Adult patients with moderate anaemia (haemoglobin 5.0-6.8 mmol/l) on the first post-operative day after first-time, non-emergent cardiac surgery are eligible. After stratification by gender, 110 patients are randomised 1:1 to either single, high-dose intravenous iron therapy (20 mg/kg ferric derisomaltose) or oral iron supplementation (100 mg ferrous sulphate orally twice daily). The primary outcome measure at the four-week follow-up is the proportion of participants who are neither anaemic (haemoglobin less-than 8.1 mmol/l in men and less-than 7.5 mmol/l in women) nor have received allogeneic red blood cells since randomisation. Secondary outcome measures include changes in haemoglobin and iron biomarkers, exercise capacity, patient-reported outcome measures and cost of care at the four-week follow-up. CONCLUSION: The results of the PICS trial may fundamentally alter future management of anaemia following cardiac surgery. FUNDING: The study is supported by Aarhus University Hospital, an unrestricted research grant by Pharmacosmos A/S (Holbæk, Denmark) and an independent grant from the Health Research Foundation of the Central Denmark Region (ISM). TRIAL REGISTRATION: EudraCT number: 2020-001389-12; Clinical Trials ID: NCT04608539.

Association between Tulathromycin Treatment for Bovine Respiratory Disease and Antimicrobial Resistance Profiles among Gut Commensals and Foodborne Bacterial Pathogens Isolated from Feces of Beef Steers.

ABSTRACT: This study was conducted to evaluate the association between a therapeutic dose of tulathromycin for bovine respiratory disease in beef steers and the antimicrobial and multidrug resistance profiles of the gastrointestinal tract commensals Escherichia coli and Enterococcus spp. and the foodborne pathogens Salmonella enterica and Campylobacter spp. isolated from fecal samples. Individual fecal samples were collected on days 0, 14, and 28 from 70 beef steers that were housed in a single pen and had been treated or not treated with tulathromycin. Samples were cultured for bacterial isolation, and isolates were tested for antimicrobial susceptibility with the broth microdilution method to determine the MICs of clinically relevant antimicrobials used in both human and veterinary medicine. Generalized linear mixed effects models were fitted to estimate the prevalence of the bacterial species and the prevalence of resistant isolates over time and between treated and nontreated cattle and of multidrug-resistant isolates. Model-adjusted mean prevalences of E. coli, Enterococcus spp., S. enterica, and Campylobacter spp. were 99.5, 85.9, 1.5, and 17.7%, respectively. The prevalence of erythromycin-resistant Enterococcus spp. was significantly higher on day 14 (59.7%) than on day 28 (22.2%). A higher prevalence of erythromycin-resistant Enterococcus spp. was found in samples from treated (59.3%) than in samples from nontreated (27.6%) animals. Multidrug resistance (three or more antimicrobial classes) was observed in 8.4% of E. coli isolates and 62.7% of Enterococcus isolates. The administration of tulathromycin was significantly associated with an increased prevalence of erythromycin-resistant Enterococcus spp. isolates.