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Frontiers in Immunology 2024Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently,... (Review)
Review
Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) is the only disease-modifying treatment with the potential to re-establish clinical tolerance towards the corresponding allergen(s). However, conventional AIT has certain drawbacks, including long treatment durations, the risk of inducing allergic side effects, and the fact that allergens by themselves have a rather low immunogenicity. To improve AIT, adjuvants can be a powerful tool not only to increase the immunogenicity of co-applied allergens but also to induce the desired immune activation, such as promoting allergen-specific Th1- or regulatory responses. This review summarizes the knowledge on adjuvants currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants that have been studied in recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan) and TLR-ligands (flagellin and CpG-ODN). The investigated adjuvants show distinct properties, such as prolonging allergen release at the injection site, inducing allergen-specific IgG production while also reducing IgE levels, as well as promoting differentiation and activation of different immune cells. In the future, better understanding of the immunological mechanisms underlying the effects of these adjuvants in clinical settings may help us to improve AIT.
Topics: Humans; Desensitization, Immunologic; Hypersensitivity; Adjuvants, Immunologic; Allergens; Aluminum Hydroxide; Adjuvants, Pharmaceutic
PubMed: 38464539
DOI: 10.3389/fimmu.2024.1348305 -
Acta Biomaterialia Apr 2024Guinea fowl eggshells have an unusual structural arrangement that is different from that of most birds, consisting of two distinct layers with different microstructures....
Guinea fowl eggshells have an unusual structural arrangement that is different from that of most birds, consisting of two distinct layers with different microstructures. This bilayered organization, and distinct microstructural characteristics, provides it with exceptional mechanical properties. The inner layer, constituting about one third of the eggshell thickness, contains columnar calcite crystal units arranged vertically as in most bird shells. However, the thicker outer layer has a more complex microstructural arrangement formed by a switch to smaller calcite domains with diffuse/interlocking boundaries, partly resembling the interfaces seen in mollusk shell nacre. The switching process that leads to this remarkable second-layer microstructure is unknown. Our results indicate that the microstructural switching is triggered by changes in the inter- and intracrystalline organic matrix. During production of the outer microcrystalline layer in the later stages of eggshell formation, the interactions of organic matter with mineral induce an accumulation of defects that increase crystal mosaicity, instill anisotropic lattice distortions in the calcite structure, interrupt epitaxial growth, reduce crystallite size, and induce nucleation events which increase crystal misorientation. These structural changes, together with the transition between the layers and each layer having different microstructures, enhance the overall mechanical strength of the Guinea fowl eggshell. Additionally, our findings provide new insights into how biogenic calcite growth may be regulated to impart unique functional properties. STATEMENT OF SIGNIFICANCE: Avian eggshells are mineralized to protect the embryo and to provide calcium for embryonic chick skeletal development. Their thickness, structure and mechanical properties have evolved to resist external forces throughout brooding, yet ultimately allow them to crack open during chick hatching. One particular eggshell, that of the Guinea fowl, has structural features very different from other galliform birds - it is bilayered, with an inner columnar mineral structure (like in most birds), but it also has an outer layer with a complex microstructure which contributes to its superior mechanical properties. This work provides novel and new fundamental information about the processes and mechanisms that control and change crystal growth during the switch to microcrystalline domains when the second outer layer forms.
Topics: Animals; Egg Shell; Chickens; Calcium Carbonate; Minerals
PubMed: 38460930
DOI: 10.1016/j.actbio.2024.03.001 -
The Science of the Total Environment May 2024This study proposed and examined a new process flowsheet for treating neutral mine drainage (NMD) from an open-pit gold mine. The process consisted of three sequential...
This study proposed and examined a new process flowsheet for treating neutral mine drainage (NMD) from an open-pit gold mine. The process consisted of three sequential stages: (1) in situ hydrotalcite (HT) precipitation; (2) low-cost carbon substrate driven microbial sulfate reduction; and (3) ferrosol reactive barrier for removing biogenic dissolved hydrogen sulfide (HS). For concept validation, laboratory-scale columns were established and operated for a 140-days period with key process performance parameters regularly measured. At the end, solids recovered from various depths of the ferrosol column were analysed for elemental composition and mineral phases. Prokaryotic microbial communities in various process locations were characterised using 16S rRNA gene sequencing. Results showed that the Stage 1 HT-treatment substantially removed a range of elements (As, B, Ba, Ca, F, Zn, Si, and U) in the NMD, but not nitrate or sulfate. The Stage 2 sulfate reducing bioreactor (SRB) packed with 70 % (v/v) Eucalyptus woodchip, 1 % (w/v) ground (<1 mm) dried Typha biomass, and 10 % (w/v) NMD-pond sediment facilitated complete nitrate removal and stable sulfate removal of ca. 50 % (50 g-SO m d), with an average HS generation rate of 10 g-HS md. The HS-removal performance of the Stage 3 ferrosol column was compared with a synthetic amorphous Fe-oxyhydroxide-amended sand control column. Although both columns facilitated excellent (95-100 %) HS removal, the control column only enabled a further ca. 10 % sulfate reduction, giving an overall sulfate removal of 56 %. In contrast, the ferrosol enabled an extra 99.9 % sulfate reduction in the SRB effluent, leading to a near complete sulfate removal. Overall, the process successfully eliminated a range of metal/metalloid contaminants, nitrate, sulfate (2500 mg-SO L in the NMD to <10 mg-SO L in the final effluent) and HS (>95 % removal). Further optimisation is required to minimise release of ferrous iron from the ferrosol barrier into the final effluent.
Topics: Hydrogen Sulfide; RNA, Ribosomal, 16S; Nitrates; Sulfates; Bioreactors; Aluminum Hydroxide; Magnesium Hydroxide
PubMed: 38460684
DOI: 10.1016/j.scitotenv.2024.171537 -
Current Biology : CB Mar 2024Restoration is increasingly seen as a necessary tool to reverse ecological decline across terrestrial and marine ecosystems. Considering the unprecedented loss of coral...
Restoration is increasingly seen as a necessary tool to reverse ecological decline across terrestrial and marine ecosystems. Considering the unprecedented loss of coral cover and associated reef ecosystem services, active coral restoration is gaining traction in local management strategies and has recently seen major increases in scale. However, the extent to which coral restoration may restore key reef functions is poorly understood. Carbonate budgets, defined as the balance between calcium carbonate production and erosion, influence a reef's ability to provide important geo-ecological functions including structural complexity, reef framework production, and vertical accretion. Here we present the first assessment of reef carbonate budget trajectories at restoration sites. The study was conducted at one of the world's largest coral restoration programs, which transplants healthy coral fragments onto hexagonal metal frames to consolidate degraded rubble fields. Within 4 years, fast coral growth supports a rapid recovery of coral cover (from 17% ± 2% to 56% ± 4%), substrate rugosity (from 1.3 ± 0.1 to 1.7 ± 0.1) and carbonate production (from 7.2 ± 1.6 to 20.7 ± 2.2 kg m yr). Four years after coral transplantation, net carbonate budgets have tripled and are indistinguishable from healthy control sites (19.1 ± 3.1 and 18.7 ± 2.2 kg m yr, respectively). However, taxa-level contributions to carbonate production differ between restored and healthy reefs due to the preferential use of branching corals for transplantation. While longer observation times are necessary to observe any self-organization ability of restored reefs (natural recruitment, resilience to thermal stress), we demonstrate the potential of large-scale, well-managed coral restoration projects to recover important ecosystem functions within only 4 years.
Topics: Animals; Anthozoa; Ecosystem; Coral Reefs; Carbonates; Calcium Carbonate
PubMed: 38460511
DOI: 10.1016/j.cub.2024.02.009 -
Scientific Reports Mar 2024Aluminum in its Al form is a metal that inhibits plant growth, especially in acidic soils (pH < 5.5). Rapid and accurate quantitative detection of Al in agricultural...
Aluminum in its Al form is a metal that inhibits plant growth, especially in acidic soils (pH < 5.5). Rapid and accurate quantitative detection of Al in agricultural soils is critical for the timely implementation of remediation strategies. However, detecting metal ions requires time-consuming preparation of samples, using expensive instrumentation and non-portable spectroscopic techniques. As an alternative, electrochemical sensors offer a cost-effective and minimally invasive approach for in situ quantification of metal ions. Here, we developed and validated an electrochemical sensor based on bismuth-modified laser-induced graphene (LIG) electrodes for Al quantitative detection in a range relevant to agriculture (1-300 ppm). Our results show a linear Al detection range of 1.07-300 ppm with a variation coefficient of 5.3%, even in the presence of other metal ions (Pb, Cd, and Cu). The sensor offers a limit of detection (LOD) of 0.34 ppm and a limit of quantification (LOQ) of 1.07 ppm. We compared its accuracy for soil samples with pH < 4.8 to within 89-98% of spectroscopic methods (ICP-OES) and potentiometric titration. This technology's portability, easy to use, and cost-effectiveness make it a promising candidate for in situ quantification and remediation of Al in agricultural soils and other complex matrices.
Topics: Soil; Graphite; Aluminum; Bismuth; Ions; Lasers; Electrochemical Techniques
PubMed: 38459204
DOI: 10.1038/s41598-024-56212-0 -
Medicine Mar 2024Vonoprazan, a novel acid suppressant and the first potassium-competitive acid blocker, has the potential to enhance the eradication rate of Helicobacter pylori due to...
Comparison of vonoprazan-based dual therapy with vonoprazan-based bismuth quadruple therapy for treatment-naive patients with Helicobacter pylori infection: A propensity score matching analysis.
Vonoprazan, a novel acid suppressant and the first potassium-competitive acid blocker, has the potential to enhance the eradication rate of Helicobacter pylori due to its robust acid-suppressing capacity. This study aimed to compare the efficacy of vonoprazan-based dual therapy (vonoprazan-amoxicillin, VA) with vonoprazan-based bismuth quadruple therapy (VBQT) as a first-line treatment for H pylori infection. This retrospective single-center non-inferiority study was conducted in China. Treatment-naive H pylori-positive patients aged 18 to 80 received one of the 2 treatment regimens at our center. The VA group received vonoprazan 20 mg twice daily and amoxicillin 1000 mg 3 times daily for 14 days, whereas the VBQT group received vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. The eradication rate was evaluated 4 to 6 weeks after treatment using the carbon-13/14 urea breath test. Propensity score matching was used to analyze eradication rates, adverse events (AEs), and patient compliance between the 2 groups. Initially, 501 patients were included, and after propensity score analysis, 156 patients were selected for the study. Intention-to-treat analysis showed eradication rates of 87.2% (95% CI, 79.8-94.6%) for the VA group and 79.5% (95% CI, 70.5-88.4%) for the VBQT group (P = .195). Per-protocol analysis demonstrated rates of 94.4% (95% CI, 89.2-99.7%) for the VA group and 96.8% (95% CI, 92.4-100%) for the VBQT group (P = .507). Non-inferiority was confirmed between the 2 groups, with P values < .025. The VA group showed a lower rate of AEs (10.3% vs 17.9%, P = .250) compared to the VBQT group. There were no significant differences in patient compliance between the 2 groups. In treatment-naive patients with H pylori infection, both the 14-day VA and VBQT regimens demonstrated comparable efficacy, with excellent eradication rates. Moreover, due to reduced antibiotic usage, lower rate of AEs, and lower costs, VA dual therapy should be prioritized.
Topics: Humans; Helicobacter Infections; Bismuth; Helicobacter pylori; Retrospective Studies; Propensity Score; Proton Pump Inhibitors; Drug Therapy, Combination; Anti-Bacterial Agents; Amoxicillin; Clarithromycin; Treatment Outcome; Pyrroles; Sulfonamides
PubMed: 38457567
DOI: 10.1097/MD.0000000000037476 -
Science Advances Mar 2024The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and...
The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic--glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.
Topics: Rats; Animals; Magnesium Oxide; Cartilage, Articular; Magnesium; Phosphatidylinositol 3-Kinases; Osteoarthritis; Nanoparticles
PubMed: 38457498
DOI: 10.1126/sciadv.adk6084 -
Scientific Reports Mar 2024The relationship between energy reserves of cold-water corals (CWCs) and their physiological performance remains largely unknown. In addition, it is poorly understood...
The relationship between energy reserves of cold-water corals (CWCs) and their physiological performance remains largely unknown. In addition, it is poorly understood how the energy allocation to different metabolic processes might change with projected decreasing food supply to the deep sea in the future. This study explores the temporal and spatial variations of total energy reserves (proteins, carbohydrates and lipids) of the CWC Desmophyllum dianthus and their correlation with its calcification rate. We took advantage of distinct horizontal and vertical physico-chemical gradients in Comau Fjord (Chile) and examined the changes in energy reserves over one year in an in situ reciprocal transplantation experiment (20 m vs. 300 m and fjord head vs. mouth). Total energy reserves correlated positively with calcification rates. The fast-growing deep corals had higher and less variable energy reserves, while the slower-growing shallow corals showed pronounced seasonal changes in energy reserves. Novel deep corals (transplanted from shallow) were able to quickly increase both their calcification rates and energy reserves to similar levels as native deep corals. Our study shows the importance of energy reserves in sustaining CWC growth in spite of aragonite undersaturated conditions (deep corals) in the present, and potentially also future ocean.
Topics: Animals; Anthozoa; Estuaries; Calcification, Physiologic; Water; Calcium Carbonate; Coral Reefs
PubMed: 38454106
DOI: 10.1038/s41598-024-56280-2 -
Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
Water Research May 2024Water quality management is a pressing global concern, and an increasingly complex issue due to climate and land-use change, legacy pollution, and the persistent release...
Water quality management is a pressing global concern, and an increasingly complex issue due to climate and land-use change, legacy pollution, and the persistent release of well-known and emerging contaminants from diffuse and point sources. The increasing availability of high-frequency monitoring data is leading existing, often heuristic approaches, to be judged inadequate. Water managers frequently rely on simple qualitative and/or quantitative approaches for decision-making, but a lack of tangible improvement in freshwater quality outcomes is demanding new and innovative approaches that rely more on physical process understanding, rather than precedent. In this study, we drew upon local geological, hydrogeological, and hydrological data to infer a high-level perceptual model of surface/groundwater interactions in a chalk stream in Dorset, UK. We used the perceptual model to interrogate spatial and temporal trends in historical water quality data and to construct reach-scale nutrient mass balances. Through novel representation with Sankey diagrams, the perceptual model highlighted the relative importance of different hydrological features. Surface/groundwater interactions were found to occur predominantly by spring flow. We demonstrate that river flow accretion was dominated by the Chalk aquifer despite only occupying ca. 15 % of the surface bedrock area, and that spring sources, whilst vital to dilute treated sewage inputs in baseflow conditions, were also major sources of legacy nitrate. Nutrient mass balances showed that sewage treatment works contributed ca. 13 % to soluble reactive phosphorus load, with groundwater accounting for ca. 48 %. Thus, a determinand often associated with point-source pollution was shown to be diffuse dominated in this river. The study demonstrated how a multi-disciplinary approach to water management, based on a comprehensive perceptual modelling approach, could identify hitherto unknown sources and relative contributors to freshwater pollution and allow flow and load apportionment studies to provide useful decision-support to manage nutrient pollution. The novel application of perceptual modelling tools, such as the Sankey diagram, allows different source attributions to be presented in an accessible manner, and can be readily transferred to other study areas.
Topics: Environmental Monitoring; Sewage; Water Quality; Rivers; Calcium Carbonate; Water Supply; Water Pollutants, Chemical
PubMed: 38452526
DOI: 10.1016/j.watres.2024.121406