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Nature Communications May 2024Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are...
Whole virus-based inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide have been critical to the COVID-19 pandemic response. Although these vaccines are protective against homologous coronavirus infection, the emergence of novel variants and the presence of large zoonotic reservoirs harboring novel heterologous coronaviruses provide significant opportunities for vaccine breakthrough, which raises the risk of adverse outcomes like vaccine-associated enhanced respiratory disease. Here, we use a female mouse model of coronavirus disease to evaluate inactivated vaccine performance against either homologous challenge with SARS-CoV-2 or heterologous challenge with a bat-derived coronavirus that represents a potential emerging disease threat. We show that inactivated SARS-CoV-2 vaccines adjuvanted with aluminum hydroxide can cause enhanced respiratory disease during heterologous infection, while use of an alternative adjuvant does not drive disease and promotes heterologous viral clearance. In this work, we highlight the impact of adjuvant selection on inactivated vaccine safety and efficacy against heterologous coronavirus infection.
Topics: Animals; COVID-19 Vaccines; Female; COVID-19; Mice; Vaccines, Inactivated; SARS-CoV-2; Aluminum Hydroxide; Disease Models, Animal; Adjuvants, Immunologic; Adjuvants, Vaccine; Antibodies, Viral; Mice, Inbred BALB C; Humans; Severe acute respiratory syndrome-related coronavirus
PubMed: 38702297
DOI: 10.1038/s41467-024-47450-x -
Medicine May 2024Compared with traditional root canal therapy (RCT), vital pulp therapy (VPT) is a personalized and minimally invasive method for the treatment of pulpitis caused by... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Compared with traditional root canal therapy (RCT), vital pulp therapy (VPT) is a personalized and minimally invasive method for the treatment of pulpitis caused by dental caries. However, there are still no clear guidelines for VPT because high-quality randomized clinical trials are scarce. This prospective cohort study evaluated the clinical efficacy of VPT with the light-curable calcium silicate-based material TheraCal LC (TH) and bioceramic material iRoot BP Plus (BP) in reversible and irreversible pulpitis permanent teeth with carious exposures.
METHODS
115 teeth with reversible or irreversible pulpitis caused by deep care were randomly divided into 2 groups. TheraCal LC and iRoot BP Plus were used for the pulp capping. Direct pulp capping (DPC), partial pulpotomy (PP) and full pulpotomy (FP) were performed based on observation of the exposed pulp. Postoperative discomforts were enquired and recorded via follow-up phone calls. Clinical and radiographic evaluations were performed 3, 6, and 12 months postoperatively.
RESULTS
The overall clinical success rate in the first year was 90.4% (47/52) in both groups. The TH group required less operating time, showed lower levels of pain, and had shorter pain duration post-operative (P < .001). According to the binary logistic regression model, preoperative pain duration was significantly correlated with the prognosis of VPT (P = .011).
CONCLUSION
VPT with TheraCal LC and iRoot BP Plus in pulpitis permanent carious teeth both achieved good clinical outcomes, and TheraCal LC can be easily operated for clinical use. Preoperative pain duration of the affected tooth might have a significant correlation with the prognosis of VPT.
Topics: Humans; Pulpitis; Calcium Compounds; Silicates; Female; Male; Pulpotomy; Adult; Prospective Studies; Dental Pulp Capping; Dental Caries; Young Adult; Treatment Outcome; Adolescent; Middle Aged; Drug Combinations; Calcium Hydroxide; Aluminum Compounds; Oxides
PubMed: 38701294
DOI: 10.1097/MD.0000000000038015 -
Micromachines Mar 2024Piezoelectric micromachined ultrasound transducers (PMUTs) have gained significant popularity in the field of ultrasound ranging and medical imaging owing to their small...
Piezoelectric micromachined ultrasound transducers (PMUTs) have gained significant popularity in the field of ultrasound ranging and medical imaging owing to their small size, low power consumption, and affordability. The scar-free "MIS" (micro-hole inter-etch and sealing) process, a novel bulk-silicon manufacturing technique, has been successfully developed for the fabrication of pressure sensors, flow sensors, and accelerometers. In this study, we utilize the MIS process to fabricate cavity diaphragm structures for PMUTs, resulting in the formation of a flat cavity diaphragm structure through anisotropic etching of (111) wafers in a 70 °C tetramethylammonium hydroxide (TMAH) solution. This study investigates the corrosion characteristics of the MIS technology on (111) silicon wafers, arranges micro-pores etched on bulk silicon around the desired cavity structure in a regular pattern, and takes into consideration the distance compensation for lateral corrosion, resulting in a fully connected cavity structure closely approximating an ortho-hexagonal shape. By utilizing a sputtering process to deposit metallic molybdenum as upper and lower electrodes, as well as piezoelectric materials above the cavity structure, we have successfully fabricated aluminum nitride (AlN) piezoelectric ultrasonic transducer arrays of various sizes and structures. The final hexagonal PMUT cells of various sizes that were fabricated achieved a maximum quality factor (Q) of 251 and a displacement sensitivity of 18.49 nm/V across a range of resonant frequencies from 6.28 MHz to 11.99 MHz. This fabrication design facilitates the achievement of IC-compatible and cost-effective mass production of PMUT array devices with high resonance frequencies.
PubMed: 38675293
DOI: 10.3390/mi15040482 -
Polymers Apr 2024Polymeric materials, renowned for their lightweight attributes and design adaptability, play a pivotal role in augmenting fuel efficiency and cost-effectiveness in...
Polymeric materials, renowned for their lightweight attributes and design adaptability, play a pivotal role in augmenting fuel efficiency and cost-effectiveness in railway vehicle development. The tailored formulation of compounds, specifically designed for additive manufacturing, holds significant promise in expanding the use of these materials. This study centers on poly(lactic acid) (PLA), a natural-based biodegradable polymeric material incorporating diverse halogen-free flame retardants (FRs). Our investigation scrutinizes the printability and fire performance of these formulations, aligning with the European railway standard EN 45545-2. The findings underscore that FR in the condensed phase, including ammonium polyphosphate (APP), expandable graphite (EG), and intumescent systems, exhibit superior fire performance. Notably, FR-inducing hydrolytic degradation, such as aluminum hydroxide (ATH) or EG, reduces polymer molecular weight, significantly impacting PLA's mechanical performance. Achieving a delicate balance between fire resistance and mechanical properties, formulations with APP as the flame retardant emerge as optimal. This research contributes to understanding the fire performance and printability of 3D-printed PLA compounds, offering vital insights for the rail industry's adoption of polymeric materials.
PubMed: 38674951
DOI: 10.3390/polym16081030 -
The Canadian Journal of Infectious... 2024The development of combinatorial adjuvants is a promising strategy to boost vaccination efficiency. Accumulating evidence indicates that manganese exerts strong...
INTRODUCTION
The development of combinatorial adjuvants is a promising strategy to boost vaccination efficiency. Accumulating evidence indicates that manganese exerts strong immunocompetence and will become an enormous potential adjuvant. Here, we described a novel combination of Mn plus aluminum hydroxide (AH) adjuvant that significantly exhibited the synergistic immune effect. . Initially, IsdB3 proteins as the immune-dominant fragment of IsdB proteins derived from () were prepared. IsdB3 proteins were identified by western blotting. Furthermore, we immunized C57/B6 mice with IsdB3 proteins plus Mn and AH adjuvant. After the second immunization, the proliferation of lymphocytes was measured by the cell counting kit-8 (CCK-8) and the level of IFN-, IL-4, IL-10, and IL-17 cytokine from spleen lymphocytes in mice and generation of the antibodies against IsdB3 in serum was detected with ELISA, and the protective immune response was assessed through challenge.
RESULTS
IsdB3 proteins plus Mn and AH obviously stimulated the proliferation of spleen lymphocytes and increased the secretion of IFN-, IL-4, IL-10, and IL-17 cytokine in mice, markedly enhanced the generation of the antibodies against IsdB3 in serum, observably decreased bacterial load in organs, and greatly improved the survival rate of mice.
CONCLUSION
These data showed that the combination of Mn and AH significantly acted a synergistic effect, reinforced the immunogenicity of IsdB3, and offered a new strategy to increase vaccine efficiency.
PubMed: 38660494
DOI: 10.1155/2024/7502110 -
Frontiers in Immunology 2024Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents (Pf) malaria but is ineffective against...
Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents (Pf) malaria but is ineffective against (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C. Both formulations induced prolonged IgG responses, with IgG1 dominance by the Alhydrogel group and high titers of all IgG isotypes by the Poly I:C counterpart. Poly I:C-adjuvanted vaccination increased splenic plasma cells, terminally-differentiated memory cells (MBCs), and precursors relative to the Alhydrogel-combined immunization. Splenic B-cells from Poly I:C-vaccinated mice revealed an antibody-secreting cell- and MBC-differentiating gene expression profile. Biological processes such as antibody folding and secretion were highlighted by the Poly I:C-adjuvanted vaccination. These findings underscore the potential of Poly I:C to strengthen immune responses against Pv malaria.
Topics: Poly I-C; Plasmodium vivax; Immunity, Humoral; Immunity, Cellular; Protozoan Proteins; Malaria Vaccines; Aluminum Hydroxide; Immunoglobulin G; Male; Animals; Plasma Cells; Female; Mice, Inbred C57BL; Recombinant Proteins; Vaccination; Adjuvants, Vaccine; Immunogenicity, Vaccine; Malaria, Vivax
PubMed: 38650939
DOI: 10.3389/fimmu.2024.1331474 -
BMC Medicine Apr 2024The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P. falciparum glutamate-rich protein (R0), has previously been produced in Lactococcus lactis and elicited functional antibodies in rodents. Here, we assess the safety and transmission-reducing efficacy of R0.6C adsorbed to aluminium hydroxide with and without Matrix-M™ adjuvant in humans.
METHODS
In this first-in-human, open-label clinical trial, malaria-naïve adults, aged 18-55 years, were recruited at the Radboudumc in Nijmegen, the Netherlands. Participants received four intramuscular vaccinations on days 0, 28, 56 and 168 with either 30 µg or 100 µg of R0.6C and were randomised for the allocation of one of the two different adjuvant combinations: aluminium hydroxide alone, or aluminium hydroxide combined with Matrix-M1™ adjuvant. Adverse events were recorded from inclusion until 84 days after the fourth vaccination. Anti-R0.6C and anti-6C IgG titres were measured by enzyme-linked immunosorbent assay. Transmission-reducing activity of participants' serum and purified vaccine-specific immunoglobulin G was assessed by standard membrane feeding assays using laboratory-reared Anopheles stephensi mosquitoes and cultured P. falciparum gametocytes.
RESULTS
Thirty-one participants completed four vaccinations and were included in the analysis. Administration of all doses was safe and well-tolerated, with one related grade 3 adverse event (transient fever) and no serious adverse events occurring. Anti-R0.6C and anti-6C IgG titres were similar between the 30 and 100 µg R0.6C arms, but higher in Matrix-M1™ arms. Neat participant sera did not induce significant transmission-reducing activity in mosquito feeding experiments, but concentrated vaccine-specific IgGs purified from sera collected two weeks after the fourth vaccination achieved up to 99% transmission-reducing activity.
CONCLUSIONS
R0.6C/aluminium hydroxide with or without Matrix-M1™ is safe, immunogenic and induces functional Pfs48/45-specific transmission-blocking antibodies, albeit at insufficient serum concentrations to result in transmission reduction by neat serum. Future work should focus on identifying alternative vaccine formulations or regimens that enhance functional antibody responses.
TRIAL REGISTRATION
The trial is registered with ClinicalTrials.gov under identifier NCT04862416.
Topics: Adolescent; Adult; Animals; Female; Humans; Male; Middle Aged; Young Adult; Adjuvants, Immunologic; Aluminum Hydroxide; Antibodies, Protozoan; Malaria Vaccines; Malaria, Falciparum; Membrane Glycoproteins; Netherlands; Plasmodium falciparum; Protozoan Proteins
PubMed: 38649867
DOI: 10.1186/s12916-024-03379-y -
ACS Omega Apr 2024This study aims to synthesize and 5-monosubstituted rhodanine derivatives as ion-sensing organics and investigate their sensing abilities. Following an easy and green...
This study aims to synthesize and 5-monosubstituted rhodanine derivatives as ion-sensing organics and investigate their sensing abilities. Following an easy and green approach to synthesis, the anion-sensing properties of the rhodanines were studied using colorimetric detection and spectroscopic methods. As a result of studies, rhodanines are found to be highly solvent-controlled colorimetric and fluorescent cyanide, mercury, and aluminum sensors. The stoichiometry of the interaction between CN and both probes was determined to be 1:1 using Job's plot analysis. The binding constants () of CN to and were calculated to be 3.25 × 10 and 7.07 × 10 M, respectively, demonstrating their high affinity for cyanide ions. The limits of detections for the and were also determined as 356 and 617 nM, respectively. In addition to detecting CN, also serves as a specific turn-off sensor for mercury and aluminum when cyanide and hydroxide are present. This enables the fluorescence intensity to be toggled on/off by alternating the addition of CN/OH and Hg/Al. Furthermore, the LOD values for Hg and Al with -CN and -OH were determined to be 414 nM and 1.35 μM, respectively. Furthermore, the turn-on binding mechanisms of and with cyanide ions were elucidated, and the experimental band gap (highest occupied molecular orbital/least unoccupied molecular orbital) energy values corroborated the proposed mechanism. Additionally, the interaction mechanism of the probes with CN was further investigated by using the H NMR technique. Collectively, these findings suggest that , , and -CN hold promise as selective and sensitive candidate sensors for CN, Hg, and Al ions.
PubMed: 38645373
DOI: 10.1021/acsomega.4c01066 -
Dental Materials Journal Jun 2024This study investigated the wettability and consistency of various endodontic sealers, both inorganic and organic, and evaluated their sealing ability of root canals...
This study investigated the wettability and consistency of various endodontic sealers, both inorganic and organic, and evaluated their sealing ability of root canals using the single-cone obturation technique, with and without ethylenediaminetetraacetic acid (EDTA) treatment. Bovine root canals were endodontically prepared and filled in preparation for the dye penetration test with toluidine blue solution. All sealers exhibited contact angles similar to or lower than dentin and displayed superior consistency. Among the sealers, organic sealers used without EDTA treatment showed reduced dye penetration compared to inorganic sealers. However, some inorganic and organic sealers showed dye penetration in the sealer and dentin of root canals subjected to EDTA treatment. In conclusion, the single-cone obturation technique, combined with these endodontic sealers, achieved close contact with root canal dentin due to their wettability and consistency. However, the sealing ability of certain sealers was influenced by EDTA treatment.
Topics: Root Canal Filling Materials; Animals; Edetic Acid; Cattle; Root Canal Obturation; Materials Testing; Wettability; Drug Combinations; Dental Leakage; Dental Pulp Cavity; Silicates; Surface Properties; Calcium Compounds; Epoxy Resins; Dental Bonding; Aluminum Compounds; In Vitro Techniques; Oxides; Calcium Hydroxide; Root Canal Preparation; Gutta-Percha; Dentin; Coloring Agents
PubMed: 38644213
DOI: 10.4012/dmj.2023-305 -
Cureus Mar 2024Various ocular manifestations associated with COVID-19 and vaccines, affecting both the anterior and posterior segments of the eye have been documented in the...
Various ocular manifestations associated with COVID-19 and vaccines, affecting both the anterior and posterior segments of the eye have been documented in the literature. In this report, we present the case of a 25-year-old male who complained of sudden-onset blurred vision and metamorphopsia in both eyes one day after receiving the second dose of the Sinopharm COVID-19 vaccine. The visual loss was painless, with no reported flashes or floaters. The patient had no significant medical or surgical history, no history of trauma, and no drug intake. Upon ocular examination, the best-corrected visual acuity was 6/60 (Snellen chart) in both eyes. The anterior segments appeared unremarkable, while fundoscopy revealed multiple yellowish-white subretinal lesions at the posterior pole of both eyes. Spectral domain optical coherence tomography (SD-OCT) confirmed the presence of subretinal fluid (SRF) with neurosensory detachment in each eye, along with bacillary layer detachment (BALAD). There were no signs of inflammation in the vitreous cavity. A diagnosis of acute posterior multifocal plaque pigment epitheliopathy (APMPPE) was established. The patient was prescribed nepafenac 0.1% drops to be instilled three times a day in both eyes and was advised to return for a follow-up examination in two weeks. At the follow-up visit, the patient's vision had improved to 6/9 in the right eye and 6/6 in the left eye, with most of the SRF absorbed. Unilateral APMPPE with BALAD has been mentioned in the literature following various COVID-19 vaccinations, but, to the best of our knowledge, this is the first case report where bilateral APMPPE with BALAD is reported. This case emphasizes the importance of a thorough eye examination for individuals experiencing ocular symptoms after receiving the COVID-19 vaccine.
PubMed: 38562362
DOI: 10.7759/cureus.55369