Supplementation of seasonal vaccine with multi-subtype neuraminidase and M2 ectodomain virus-like particle improves protection against homologous and heterologous influenza viruses in aged mice.

The conventional inactivated split seasonal influenza vaccine offers low efficacy, particularly in the elderly and against antigenic variants. Here, to improve the efficacy of seasonal vaccination for the elderly population, we tested whether supplementing seasonal bivalent (H1N1 + H3N2) split (S) vaccine with M2 ectodomain repeat and multi-subtype consensus neuraminidase (NA) proteins (N1 NA + N2 NA + flu B NA) on a virus-like particle (NA-M2e) would induce enhanced cross-protection against different influenza viruses in aged mice. Immunization with split vaccine plus NA-M2e (S + NA-M2e) increased vaccine-specific IgG antibodies towards T-helper type 1 responses and hemagglutination inhibition titers. Aged mice with NA-M2e supplemented vaccination were protected against homologous and heterologous viruses at higher efficacies, as evidenced by preventing weight loss, lowering lung viral loads, inducing broadly cross-protective humoral immunity, and IFN-γ+ CD4 and CD8 T cell responses than those with seasonal vaccine. Overall, this study supports a new strategy of NA-M2e supplemented vaccination to enhance protection against homologous and antigenically different viruses in the elderly.

Febrile Phase Soluble Urokinase Plasminogen Activator Receptor and Olfactomedin 4 as Prognostic Biomarkers for Severe Dengue in Adults.

BACKGROUND: Dengue cases continue to rise and can overwhelm healthcare systems during outbreaks. In dengue, neutrophil mediators, soluble urokinase plasminogen activator receptor (suPAR) and olfactomedin 4, and mast cell mediators, chymase and tryptase, have not been measured longitudinally across the dengue phases. The utility of these proteins as prognostic biomarkers for severe dengue has also not been assessed in an older adult population. METHODS: We prospectively enrolled 99 adults with dengue-40 dengue fever, 46 dengue with warning signs and 13 severe dengue, along with 30 controls. Plasma levels of suPAR, olfactomedin 4, chymase and tryptase were measured at the febrile, critical and recovery phases in dengue patients. RESULTS: The suPAR levels were significantly elevated in severe dengue compared to the other dengue severities and controls in the febrile (P < .001), critical (P < .001), and recovery (P = .005) phases. In the febrile phase, suPAR was a prognostic biomarker of severe dengue, with an AUROC of 0.82. Using a cutoff derived from Youden's index (5.4 ng/mL) and an estimated prevalence of severe dengue (16.5%) in our healthcare institution, the sensitivity was 71.4% with a specificity of 87.9% in the febrile phase, and the positive and negative predictive values were 54.7% and 95.8%, respectively. Olfactomedin 4 was elevated in dengue patients but not in proportion to disease severity in the febrile phase (P = .04) There were no significant differences in chymase and tryptase levels between dengue patients and controls. CONCLUSIONS: In adult dengue, suPAR may be a reliable prognostic biomarker for severe dengue in the febrile phase.

Perfluoroalkyl substances in food contact materials: preliminary investigation in Vietnam and global comparison.

Per- and polyfluoroalkyl substances (PFASs) are a group of concerned persistent toxic substances, especially for their application or unintentional formation in food contact materials (FCMs). However, information about the occurrence, sources, and fate of these pollutants in food packaging materials from Vietnam as well as Southeast Asian countries is probably still obscured. In this study, levels of 13 perfluoroalkyl carboxylic acids (PFCAs) and 4 sulfonates (PFSs) were determined in various types of food packaging samples collected from Vietnamese markets. Generally low concentrations of total 17 PFASs (median 0.341; max 624 ng/g) suggested that these compounds were mainly inadvertently produced rather than intentionally added to the packaging materials. A few mochi paper tray samples had relatively high PFAS levels (372-624 ng/g), which were dominated by long-chain (C8-C12) PFCAs. A comprehensive and updated overview of PFASs in FCMs from different countries in the world was also provided. Current database could not provide conclusive trends of PFAS concentrations and profiles in FCMs between continents and countries. The highest levels up to ppm were reported for PFCAs (e.g., PFBA, PFHxA, PFOA, and PFDA) and several fluorotelomer alcohols and carboxylic acids, while PFSs were almost absent in FCMs. FPASs can emit from FCMs, migrate to food, and then contribute to dietary exposure in humans and animals. Additional investigations on the occurrence, sources, behavior and fate, and impacts of PFASs in FCMs are critically needed, especially in emerging and developing countries.

Chronic allergic asthma induces T-cell exhaustion and impairs virus clearance in mice.

BACKGROUND: Allergic asthma, one of the most common types of asthma, is thought to be highly susceptible to respiratory viral infections; however, its pathological mechanism needs to be elucidated. Recent studies have found impaired T-cell function in asthmatic mice. Therefore, we aimed to investigate the way by which asthma induction affects T-cell exhaustion in the lungs and assess the relationship between T-cell exhaustion and influenza viral infection. METHODS: Chronic allergic asthma mice were induced by intranasal injection of ovalbumin for 6 weeks and asthmatic features and T cell populations in lung or airway were assessed. To determine the influenza virus susceptibility, control and asthma mice were challenged with the human influenza virus strain A/Puerto Rico/8/1934 H1N1 and evaluated the survival rate, lung damage, and virus titer. RESULTS: Six weeks of OVA sensitization and challenge successfully induced chronic allergic asthma in a mouse model showing significant increase of sera IgE level and broncho-pathological features. A significant decrease in interferon-γ-producing T-cell populations and an increase in exhausted T-cell populations in the lungs of OVA-induced asthmatic mice were observed. Asthmatic mice were more susceptible to influenza virus infection than control mice showing lower survival rate and higher virus titer in lung, and a positive correlation existed between T-cell exhaustion in the lung and virus titer. CONCLUSIONS: Asthma induction in mice results in the exhaustion of T-cell immunity, which may contribute to the defective capacity of viral protection. This study demonstrates a correlation between asthma conditions and viral susceptibility by investigating the functional characteristics of T-cells in asthma. Our results provide insights into the development of strategies to overcome the dangers of respiratory viral disease in patients with asthma.

Adjuvant effects of combination monophosphoryl lipid A and poly I:C on antigen-specific immune responses and protective efficacy of influenza vaccines.

Toll-like receptor (TLR) agonists improve vaccine immunogenicity and efficacy, but they are currently unlicensed as adjuvants in influenza vaccines. This study aimed to investigate whether a combination of monophosphoryl lipid A (MPL, a TLR4 agonist) and polyriboinosinic polyribocytidylic acid (poly I:C, a TLR3 agonist) can enhance the protective efficacy of an inactivated A/Puerto Rico/8/1934 (A/PR8) H1N1 influenza vaccine against homologous influenza infection and minimize illness outcomes. Results showed that combination MPL and poly I:C adjuvanted influenza vaccination increased the production of antigen-specific antibodies, decreased the levels of cytokines and cellular infiltrates at the infection sites, and induced significant memory T and B cell responses in mice. The results of this study suggest that the combination of MPL and poly I:C can be developed into a possible adjuvant for enhancing the efficacy of influenza vaccines.

Cytogenetic Characteristics of de novo Acute Myeloid Leukemia in Southern Vietnam.

BACKGROUND: The cytogenetic characteristics are important factors for risk stratification at diagnosis of acute myeloid leukemia (AML); however, cytogenetic profile of Vietnamese patients with AML remains undetermined. In this study, we present the chromosomal data of de novo AML patients in Southern Vietnam. METHODS: We performed cytogenetic testing for 336 AML patients using G banding. If the patients had suspected abnormalities, fluorescence in situ hybridization with probes of inv(3)(q21q26)/t(3;3)(q21;q26), 5q31, 7q31, t(8;21)(q21.3;q22), 11q23, t(15;17)(q24;q21), inv(16)(p13q22)/t(16;16)(p13;q22)were analyzed. Patients without above aberrations or with normal karyotype were tested by fluorescence in situ hybridization using probe 11q23. RESULTS: We found that the median age was 39 years. According to French - American - British classification, AML-M2 is the most frequent type with 35.1%. Chromosomal abnormalities were detected in 208 cases, accounting for 61.9%. Among structural abnormalities, t(15;17) was the most common (19.6%), followed by t(8;21) and inv (16)/t(16;16) in 10.1% and 6.2%, respectively. In perspective of chromosomal numerical abnornmalities, loss of sex chromosomes are the most common (7.7%), followed by +8 in 6.8%, -7/del(7q) in 4.4%, +21 in 3.9% and -5/del (5q) in 2.1%. The prevalence of addditional cytogenetic aberrations accompanying with t(8;21) and inv(16)/t(16;16) were 82.4% and 52.4%, repectively. None of +8 cases was associated with t(8;21). Regarding cytogenetic risk assessment according to European Leukemia Net 2017, there were 121 (36%) patients in favorable-risk, 180 (53.6%) in intermediate-risk and 35 (10.4%) in adverse-risk group. CONCLUSION: In conclusion, this is the first comprehensive cytogenetic profile of Vietnamese patients diagnosed with de novo AML, which helps clinical doctors in prognostic classification for AML patients in Southern Vietnam.

Antiracism in leading public health universities, journals and funders: commitments, accountability and the decision-makers.

INTRODUCTION: Two years since the murder of George Floyd, there has been unprecedented attention to racial justice by global public health organisations. Still, there is scepticism that attention alone will lead to real change. METHODS: We identified the highest-ranked 15 public health universities, academic journals and funding agencies, and used a standardised data extraction template to analyse the organisation's governance structures, leadership dynamics and public statements on antiracism since 1 May 2020. RESULTS: We found that the majority of organisations (26/45) have not made any public statements in response to calls for antiracism actions, and that decision-making bodies are still lacking diversity and representation from the majority of the world's population. Of those organisations that have made public statements (19/45), we identified seven types of commitments including policy change, financial resources, education and training. Most commitments were not accompanied by accountability measures, such as setting goals or developing metrics of progress, which raises concerns about how antiracism commitments are being tracked, as well as how they can be translated into tangible action. CONCLUSION: The absence of any kind of public statement paired with the greater lack of commitments and accountability measures calls into question whether leading public health organisations are concretely committed to racial justice and antiracism reform.

Protective and vaccine dose-sparing efficacy of Poly I:C-functionalized calcium phosphate nanoparticle adjuvants in inactivated influenza vaccination.

Adjuvants are required to increase the immunogenicity and efficacy of vaccination and enable vaccine dose sparing. Polyinosinic-polycytidylic acid (Poly I:C), a toll-like receptor 3 agonist, is a promising adjuvant candidate that can induce cell-mediated immune responses; however, it remains unlicensed owing to its low stability and toxicity. Calcium phosphate (CaP), a biocompatible and biodegradable nanoparticle, is widely used in biomedicine for stable and targeted drug delivery. In this study, we developed Poly I:C-functionalized CaP (Poly-CaP) and evaluated its vaccine adjuvant efficacy in vitro and in vivo. A half dose of Poly-CaP nanoparticles showed similar efficacy to a full dose of soluble Poly I:C in stimulating bone marrow-derived dendritic cells and macrophages to secrete proinflammatory cytokines and express their activation markers. Immunization with a half dose of inactivated influenza vaccine in the presence of Poly I:C or Poly-CaP adjuvants induced sufficient antigen-specific humoral responses after boost immunization. Immunization with Poly I:C, CaP, or Poly-CaP-adjuvanted with a half dose of influenza vaccine showed comparable protective efficacy against lethal virus infection, with lower weight loss and virus titer than a full dose of influenza vaccine. The Poly-CaP adjuvant was effective in stimulating antigen-specific CD4+ T cell proliferation in the lungs. Collectively, our results showed that the Poly-CaP adjuvant enhanced antigen-specific cell-mediated immunity and humoral immune responses with vaccine dose-sparing effects, suggesting its potential as a novel vaccine adjuvant candidate.

Controlled release of naringenin from soft hydrogel contact lens: An investigation into lens critical properties and in vitro release.

The naringenin (NAR)-impregnated hydrogel lenses (nesofilcon A material) were manufactured in this study with the feasibility to achieve controlled daily drug release. The lenses were fabricated using a comparable commercial-standard process, utilizing injection molding and thermal curing approaches. NAR-loaded lenses were prepared by both direct entrapment and 'soak and release' methods. Their critical properties were tested to ISO standards and comparable to the commercial lenses. NAR was fully characterized by studying its physical and chemical stability throughout the manufacturing processes using thermal analysis, high performance liquid chromatography and X-ray diffraction analysis. The NAR-loaded lenses showed > 97% light transmission, >75% water content, 0.50-0.53 ± 0.06 MPa tensile strength, with a lens diameter of 14.1 ± 0.1 mm. Lens polymerization kinetics were studied using differential scanning calorimetry. NAR released from the lens, prepared by a direct entrapment approach, followed a diffusion-controlled mechanism, and provided a controlled drug release of 72-82% for 24 h. A faster release rate was observed for NAR-loaded lenses prepared by a soak and release method, with over 90% of NAR was releasedin the first five hours.

Functional NK Cell Activation by Ovalbumin Immunization with a Monophosphoryl Lipid A and Poly I:C Combination Adjuvant Promoted Dendritic Cell Maturation.

Natural killer (NK) cells are one of the types of innate immune cells to remove pathogen-infected cells and modulate inflammatory immune responses. Recent studies have revealed that NK cells could enhance vaccine efficacy by coordinating the innate and adaptive immune responses. In this study, we have evaluated the efficacy of intranasal ovalbumin (OVA) immunization with a monophosphoryl lipid A (MPL) and polyriboinosinic polyribocytidylic acid (poly I:C) combination adjuvant in promoting NK cell recruitment, differentiation, and activation. The frequencies of NK cells were positively correlated with those of dendritic cells (DCs) at the site of immunization. Moreover, the activated NK cells and DCs by the MPL + poly I:C combination adjuvant induced activations of each other cells in vitro. Taken together, this study suggested that the MPL and poly I:C combination adjuvant in OVA vaccination mediated NK cell activation and cellular crosstalk between NK cells and DCs, suggesting a promising vaccine adjuvant candidate for promoting cellular immune responses.

Monophosphoryl Lipid A and Poly I:C Combination Adjuvant Promoted Ovalbumin-Specific Cell Mediated Immunity in Mice Model.

Induction of antigen-specific cell-mediated immunity (CMI), as well as humoral immunity, is critical for successful vaccination against various type of pathogens. Toll-like receptor (TLR) agonists have been developed as adjuvants to promote vaccine efficacy and induce appropriate immune responses. Monophosphoryl lipid A (MPL); a TLR4 agonist, and Poly I:C; a TLR3 agonist, are known as a strong immuno-stimulator which induce Th1 response. Many studies proved and compared the efficacy of each adjuvant, but no study has investigated the combination of them. Using ovalbumin protein antigen, MPL+Poly I:C combination induced more effective antigen-specific CMI response than single adjuvants. Production of inflammatory cytokines, recruitment of innate immune cells and antigen-specific CD4/CD8 memory T cell at the immunized site had been significantly enhanced by MPL+Poly I:C combination. Moreover, MPL+Poly I:C combination enhanced ovalbumin-specific serum IgG, IgG1, and IgG2c production and proliferative function of CD4 and CD8 T cells after in vitro ovalbumin peptide stimulation. Taken together, these data suggest that the combination of MPL and Poly I:C has a potency as a CMI-inducing vaccine adjuvant with synergistically increased effects.

Pharmaceutical-loaded contact lenses as an ocular drug delivery system: A review of critical lens characterization methodologies with reference to ISO standards.

Therapeutic contact lenses for ocular drug delivery have received considerable interest as they can potentially enhance ocular bioavailability, increase patient compliance, and reduce side effects. Along with the successful in vitro and in vivo studies on sustained drug delivery through contact lenses, lens critical properties such as water content, optical transparency and modulus have also been investigated. Aside from issues such as drug stability or burst release, the potential for the commercialization of pharmaceutical-loaded lenses can be limited by the alteration of lens physical and chemical properties upon the incorporation of therapeutic or non-therapeutic components. This review outlines advances in the use of pharmaceutical-loaded contact lenses and their relevant characterization methodologies as a potential ocular drug delivery system from 2010 to 2020, while summarizing current gaps and challenges in this field. A key reference point for this review is the relevant ISO standards on contact lenses, relating to the associated characterization methodologies. The content of this review is categorized based on the chemical, physical and mechanical properties of the loaded lens with the shortcomings of such analytical technologies examined.

Application of WRF-Chem to simulate air quality over Northern Vietnam.

The WRF-Chem (Weather Research and Forecasting with Chemistry) model is implemented and validated against ground-based observations for meteorological and atmospheric variables for the first time in Northern Vietnam. The WRF-Chem model was based on HTAPv2 emission inventory with MOZCART chemical-aerosol mechanism to simulate atmospheric variables for winter (January) and summer (July) of 2014. The model satisfactorily reproduces meteorological fields, such as temperature 2 m above the ground and relative humidity 2 m above the ground at 45 NCHMF meteorological stations in January, but lower agreement was found in those simulations of July. PM10 and PM2.5 concentrations in January showed good temporal and spatial agreements to observations recorded at three CEM air monitoring stations in Phutho, Quangninh, and Hanoi, with correlation coefficients of 0.36 and 0.59. However, WRF-Chem model was underestimated with MFBs from - 27.9 to - 118.7% for PM10 levels and from - 34.2 to - 115.1% for PM2.5 levels. It has difficulty in capturing day-by-day variation of PM10 and PM2.5 concentrations at each station in July, but MFBs were in the range from - 27.1 to - 40.2% which is slightly lower than those in January. It suggested that further improvements of the model and local emission data are needed to reduce uncertainties in modeling the distribution of atmospheric pollutants. Assessment of biomass burning emission on air quality in summer was analyzed to highlight the application aspect of the WRF-Chem model. The study may serve as a reference for future air quality modeling using WRF-Chem in Vietnam.

Chemical characterization and source apportionment of ambient nanoparticles: a case study in Hanoi, Vietnam.

PM0.1 has been believed to have adverse short- and long-term effects on human health. However, the information of PM0.1 that is needed to fully evaluate its influence on human health and environment is still scarce in many developing countries. This is a comprehensive study on the levels, chemical compositions, and source apportionment of PM0.1 conducted in Hanoi, Vietnam. Twenty-four-hour samples of PM0.1 were collected during the dry season (November to December 2015) at a mixed site to get the information on mass concentrations and chemical compositions. Multiple linear regression analysis was utilized to investigate the simultaneous influence of meteorological factors on fluctuations in the daily levels of PM0.1. Multiple linear regression models could explain about 50% of the variations of PM0.1 concentrations, in which wind speed is the most important variable. The average concentrations of organic carbon (OC), elemental carbon (EC), water-soluble ions (Ca2+, K+, Mg2+, Na+, NH4+, Cl-, NO3-, SO42-, C2O42-), and elements (Be, Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sb, Ba, Tl, Pb, Na, Fe, Mg, K, and Ca) were 2.77 ± 0.90 µg m-3, 0.63 ± 0.28 µg m-3, 0.88 ± 0.39 µg m-3, and 0.05 ± 0.02 µg m-3, accounting for 51.23 ± 9.32%, 11.22 ± 2.10%, 16.28 ± 2.67%, and 1.11 ± 0.94%, respectively. A positive matrix factorization model revealed the contributions of five major sources to the PM0.1 mass including traffic (gasoline and diesel emissions, 46.28%), secondary emissions (31.18%), resident/commerce (12.23%), industry (6.05%), and road/construction (2.92%).

A treat and extend protocol with Aflibercept for cystoid macular oedema secondary to central retinal vein occlusion - an 18-month prospective cohort study.

BACKGROUND: To evaluate the safety and efficacy of a treat-and-extend protocol of aflibercept for cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO). METHODS: Twenty patients with CMO secondary to CRVO were included in this prospective cohort study. After 3 loading 4-weekly injections, treatment intervals were increased by 2 weeks if there was no clinical activity, to a maximum of 12 weeks. If clinical activity recurred or persisted, the interval between injections was shortened by 2 weeks, to a minimum of 4 weeks. Main outcome measures were change in visual acuity and the proportion of patients gaining 15 or more Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from baseline at 6, 12 and 18 months. RESULTS: Mean BCVA gain from baseline was 19.7 ± 13.8, 22.2 ± 13.9 and 21.9 ± 15.8 ETDRS letters at 6, 12 and 18 months, respectively. Sixty-five percent of patients gained 15 or more ETDRS letters at 6 months, increasing to 70.6% at 12 and 18 months. Patients received 5.0 [4.0 to 6.0], 8.5 [8.0 to 10.3] and 11.0 [9.0 to 12.5] injections by 6, 12 and 18 months, respectively. CONCLUSIONS: The visual outcomes achieved with a treat-and-extend protocol in this study were similar to the pivotal trials of aflibercept for CMO secondary to CRVO, which used monthly and then as-needed protocols. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, registration number ACTRN12615000417583, 01/05/2015.

Emission Characteristics of Polycyclic Aromatic Hydrocarbons and Nitro-Polycyclic Aromatic Hydrocarbons from Open Burning of Rice Straw in the North of Vietnam.

This research investigated the distribution and contribution of polycyclic aromatic hydrocarbons (PAHs) and nitro-polycyclic aromatic hydrocarbons (NPAHs) bound to particulate matter (PM) emitted from open burning of rice straw (RS) into the atmosphere in the north of Vietnam. The experiments were conducted to collect PM2.5 and total suspended particulates (TSP) prior to and during burning in the period of 2016-2018 in suburban areas of Hanoi. Nine PAHs and 18 NPAHs were determined using the HPLC-FL system. The results showed that the proportion of RS burning seasonally affects the variation of PAHs emission in atmospheric environment. The levels of nine PAHs from RS burning were 254.4 ± 87.8 µg g-1 for PM2.5 and 209.7 ± 89.5 µg g-1 for TSP. We observed the fact that, although fluoranthene (Flu) was the most abundant PAH among detected PAHs both in PM2.5 and TSP, the enrichment of Flu in TSP from burning smoke was higher than that in PM2.5 while the contribution of benzo[a]pyrene (BaP) and indeno[1,2,3- cd]pyrene (IDP) in PM2.5 from burning smoke were much higher than those in TSP. This research found that 1-nitropyrene (1-NP) and 6-nitrochrysene (6-NC) emit from RS burning with the same range with those from wood burning. The 2-nitrofluorene (2-NF) and 2-nitropyrene (2-NP) released from RS burning as the secondary NPAHs. This research provides a comprehensive contribution characterization of PAHs and NPAHs in PM with different size emitted from traditional local rice straw burning in the north of Vietnam. The results help to clarify the environmental behavior of toxic organic compounds from RS burning in Southeast Asia.

Polycyclic aromatic hydrocarbons and nitropolycyclic aromatic hydrocarbons in particulates emitted by motorcycles.

We determined eleven PAHs and four NPAHs in particulates and regulated pollutants (CO, CO2, HC, NOx, PM) exhausted from motorcycles to figure out the characteristics of motorcycle exhausts. Fluoranthene and pyrene accounted for more than 50% of the total detected PAHs. Among four detected NPAHs, 6-nitrochrysene and 7-nitrobenz[a]anthracene were the predominant NPAHs and were highly correlated relationship with their parent PAHs (R = 0.93 and 0.97, respectively). The PM and HC emissions tended to be close to the PAH emissions. NOx and NPAHs were negatively correlated. Despite their small engine size, motorcycles emitted much more PM and PAHs, showed stronger PAH-related carcinogenicity and indirect-acting mutagenicity, but weaker NPAH-related direct-acting mutagenic potency than automobiles. This is the first study to analyze both PAHs and NPAHs emitted by motorcycles, which could provide useful information to design the emission regulations and standards for motorcycles such as PM.

Synthesis and pharmacological characterization of a potent, orally active p38 kinase inhibitor.

Inhibitors of the MAP kinase p38 provide a novel approach for the treatment of osteoporosis, inflammatory disorders, and cancer. We have identified N-(3-tert-butyl-1-methyl-5-pyrazolyl)-N'-(4-(4-pyridinylmethyl)phenyl)urea as a potent and selective p38 kinase inhibitor in biochemical and cellular assays. This compound is orally active in two acute models of cytokine release (TNF-induced IL-6 and LPS-induced TNF) and a chronic model of arthritis (20-day murine collagen-induced arthritis).