Uptake and disposition of inhaled methanol vapor in humans.

Methanol is a widely used solvent and a potential fuel for motor vehicles. Human kinetic data of methanol are sparse. As a basis for biological exposure monitoring and risk assessment, we studied the inhalation toxicokinetics of methanol vapor in four female and four male human volunteers during light physical exercise (50 W) in an exposure chamber. The relative uptake of methanol was about 50% (range 47-53%). Methanol in blood increased from a background level of about 20 to 116 and 244 microM after 2 h exposure at 0, 100 ppm (131 mg/m3) and 200 ppm (262 mg/m3), respectively. Saliva showed substantially higher levels than blood immediately after exposure. This difference disappeared in a few minutes; thereafter the concentrations and time courses in blood, urine, and saliva were similar, with half times of 1.4, 1.7, and 1.3 h, respectively. The postexposure decrease of methanol in exhaled air was faster, with a half time of 0.8 h. The methanol concentrations were approximately twice as high in all four types of biological samples at 200 compared to 100 ppm. No increase in urinary formic acid was seen in exposed subjects. Our study indicates non-saturated, dose-proportional kinetics of methanol up to 200 ppm for 2 h. No gender differences were detected. Similar, parallel patterns were seen with regard to the methanol time courses in blood, urine, and saliva, whereas the concentration in exhaled air decreased markedly faster. Thus, apart from blood and urine, saliva also seems suitable for biomonitoring of methanol exposure.     

Using the Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM) Approach to Assess the Strength of Evidence on Associations between Dietary Patterns and All-Cause Mortality

Dietary guidelines should be underpinned by high-quality evidence. Quality assessment methods that reflect traditional evidence hierarchies prioritise evidence from randomised controlled trials (RCTs). The Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM) approach is an alternative quality assessment method for research questions that for practical and/or ethical reasons, cannot be answered using RCTs. The aim of this study was to investigate how the HEALM approach could be used to assess the strength of evidence on associations between dietary patterns and all-cause mortality (a research question that is difficult to answer using RCTs). Two data sources were used: an existing systematic review of dietary patterns and all-cause mortality that synthesised evidence from observational studies; and an overview of reviews that was conducted to summarise relevant evidence from mechanistic and intervention studies. A set of four criteria were developed and used in the application of HEALM. Using different datasets in combination, the strength of evidence was rated as ‘Grade B: moderate/suggestive’ or ‘Grade C: insufficient/inconclusive’. HEALM is a novel approach for integrating and assessing the strength of evidence from mechanistic, intervention, and observational studies. Further research is needed to address the practical challenges that were identified in the application of HEALM.     

The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination

Background The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies.Methods Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens.Results MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse.Conclusion Tumour-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi)personalised strategies. Subject terms: Tumour immunology, Translational research     

The Microalgae Phaeodactylum tricornutum Is Well Suited as a Food with Positive Effects on the Intestinal Microbiota and the Generation of SCFA: Results from a Pre-Clinical Study

Microalgae such as Phaeodactylum tricornutum (PT) are a sustainable source of nutrients, especially eicosapentaenoic acid (EPA), fucoxanthin (Fx), and chrysolaminarin (Chrl), the concentrations of which can vary depending on the culture conditions. We generated three types of diets containing either an EPA- and Fx-rich (EPA/Fx) or Chrl-rich microalgae (with 5, 15, or 25% added to the diet) or an isocaloric control diet (CD). These diets were evaluated over 14 days in young C57BL/6J mice for safety and bioavailability, short-chain fatty acid (SCFA) production, and microbiome analysis. Both microalgae diets increased body weight gain dose-dependently compared to the CD. Microalgae-derived EPA was well absorbed, resulting in increased liver and fat tissue levels and a decrease in the n-6:n-3 ratio in liver tissue. Both microalgae diets increased the production of selected SCFA and decreased the Firmicutes/Bacteriodota ratio, whereas the Chrl-rich diet led to an increase in Akkermansia. Doses of up to 4621 mg Chrl, 920 mg EPA, and 231 mg Fx per kg body weight daily were tolerated without adverse effects. This pre-clinical study shows that PT is suitable for mouse feed, with positive effects on microbiota composition and SCFA production, suggesting beneficial effects on gut health.     

Training interventions for healthcare providers offering group-based patient education. A scoping review

ObjectivesTo provide overview of research on training interventions for healthcare providers aimed at promoting competencies in delivering group-based patient education.MethodsA systematic literature search identified relevant studies. Data was extracted on training details, study design, outcomes and experiences. Results were summarized and qualitative data analyzed using content analysis.ResultsTwenty-seven studies exploring various training interventions were included. Ten studies used qualitative methods, eight quantitative and nine mixed methods. Use of a comparison group, validated instruments and follow-up measures was rare. Healthcare providers’ reactions to training were mostly positive. Several studies indicated positive short-term effects on self-efficacy and knowledge. Results on observed skills and patient outcomes were inconclusive. Results on healthcare providers’ experience of delivery of group-based patient education following training were categorized into 1) Benefits of training interventions, 2) Barriers to implementation and 3) Delivery support.ConclusionsFurther evaluation of training for healthcare providers delivering group-based patient education is needed before conclusions on training efficacy can be drawn. The results indicate an expanding research field still in maturation.Practice implicationsEfficacy studies evaluating theoretically grounded training with clear attention on group facilitation and follow-up support are needed. Inclusion of validated instruments and long-term outcomes is encouraged.     

Small‐Angle X‐Ray Scattering Measurements on Amphiphilic Polymer Conetworks Swollen in Orthogonal Solvents

Amphiphilic polymer conetworks (APCNs), which combine two different polymer nanophases, have a broad range of applications that involve their unique potential to separately swell one of these nanophases in a selective solvent. Little is known about the structural changes of such APCNs upon swelling in dependence on the topology. Here, conetworks composed of poly(2‐ethylhexyl acrylate) crosslinked by poly(2‐methyl‐2‐oxazoline) (PMOx) are investigated with small‐angle X‐ray scattering in dry and swollen state using the orthogonal solvents water and toluene. The data clearly show that the structural changes induced by swelling are strongly dependent on the topology of the APCNs. While water leads to fusion of PMOx phases resulting in larger structures than found in the dry APCN, toluene is only swelling the hydrophobic phases without structural changes.     

Evaluation of a new point-of-care test to determine prior dengue infection for potential use in pre-vaccination screening

ObjectiveVaccination with the first licensed dengue vaccine is recommended only for those who have had previous infection with dengue virus (DENV). A point-of-care test with the desired sensitivity of 95% and specificity of 98% could facilitate pre-vaccination screening. We evaluated a newly developed, automated dengue immunoglobulin fluorescence immunoassay for determining dengue serostatus.MethodsWe used serum samples collected just prior to a mass dengue vaccination in Cebu, Philippines. Healthy children residing in Bogo and Balamban who would be 9–14 years old at the time of the mass dengue vaccination were eligible to participate. We evaluated the ichroma? II dengue fluorescence immunoassay (Boditech Med Incorporated, Gang-won-do, Republic of Korea) using a neutralization test (NT) as the reference assay.ResultsWe enrolled 2996 children (mean age 10.39 years, 51.7% female) in the cohort and included a subsample of 1000 (mean age 10.56 years, 54.4% female) in this study. Of the 1000 children, 86/1000 (8.6%) tested seronegative and 914/1000 (91.4%) seropositive for DENV antibodies by neutralization testing. Compared with the NT, the dengue IgG fluorescence immunoassay had an overall specificity of 90.7% (95%CI: 82.5–95.9%) and a sensitivity of 91.8% (95%CI: 89.8–93.5%) for determining dengue seropositivity. The sensitivity declined to 51.2% (42.3–61.0%) for the detection of the subset with a monotypic dengue profile.ConclusionThe insufficient specificity and sensitivity (particularly in the detection of a previous monotypic dengue infection) would render the test, in its current state, inadequate for pre-vaccination screening. Considering its user-friendly interphase and possibility of point-of-care use, the test could be further developed and validated to improve its performance characteristics.