Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers

The aim of this work was to investigate alternative safe and effective permeation enhancers for buccal peptide delivery. Basic amino acids improved insulin solubility in water while 200 and 400 µg/mL lysine significantly increased insulin solubility in HBSS. Permeability data showed a significant improvement in insulin permeation especially for 10 µg/mL of lysine (p < 0.05) and 10 µg/mL histidine (p < 0.001), 100 µg/mL of glutamic acid (p < 0.05) and 200 µg/mL of glutamic acid and aspartic acid (p < 0.001) without affecting cell integrity; in contrast to sodium deoxycholate which enhanced insulin permeability but was toxic to the cells. It was hypothesized that both amino acids and insulin were ionised at buccal cavity pH and able to form stable ion pairs which penetrated the cells as one entity; while possibly triggering amino acid nutrient transporters on cell surfaces. Evidence of these transport mechanisms was seen with reduction of insulin transport at suboptimal temperatures as well as with basal-to-apical vectoral transport, and confocal imaging of transcellular insulin transport. These results obtained for insulin is the first indication of a possible amino acid mediated transport of insulin via formation of insulin-amino acid neutral complexes by the ion pairing mechanism

Farmers review of Best Management Practices: drivers and barriers as seen by adopters and non-adopters

Assessing farmers’ intention to adopt best management practices across eight European countrie

Effectiveness and economic analysis of the whole cell/recombinant B subunit (WC/rbs) inactivated oral cholera vaccine in the prevention of traveller's diarrhoea

<p>Abstract</p> <p>Background</p> <p>Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS) in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published.</p> <p>Methods</p> <p>A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS), Dukoral^®for the prevention of traveller's diarrhoea (TD) was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005.</p> <p>Results</p> <p>The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days) subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 € per traveller.</p> <p>Conclusion</p> <p>According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.</p

Ocular inflammatory events following COVID-19 vaccination: a multinational case series

Background: Inflammatory adverse events following COVID-19 vaccination are being reported amidst the growing concerns regarding vaccine’s immunogenicity and safety, especially in patients with pre-existing inflammatory conditions. Methods: Multinational case series of patients diagnosed with an ocular inflammatory event within 14 days following COVID-19 vaccination collected from 40 centres over a 3 month period in 2021. Results: Seventy patients presented with ocular inflammatory events within 14 days following COVID-19 vaccination. The mean age was 51 years (range, 19–84 years). The most common events were anterior uveitis (n = 41, 58.6%), followed by posterior uveitis (n = 9, 12.9%) and scleritis (n = 7, 10.0%). The mean time to event was 5 days and 6 days (range, 1–14 days) after the first and second dose of vaccine, respectively. Among all patients, 36 (54.1%) had a previous history of ocular inflammatory event. Most patients (n = 48, 68.6%) were managed with topical corticosteroids. Final vision was not affected in 65 (92.9%), whereas 2 (2.9%) and 3 (4.3%) had reduction in visual acuity reduced by ≤3 lines and &gt; 3 lines, respectively. Reported complications included nummular corneal lesions (n = 1, 1.4%), cystoid macular oedema (n = 2, 2.9%) and macular scarring (n = 2, 2.9%). Conclusion: Ocular inflammatory events may occur after COVID-19 vaccination. The findings are based on a temporal association that does not prove causality. Even in the possibility of a causal association, most of the events were mild and had a good visual outcome

Intermediate hyperglycaemia and 10-year mortality in resource-constrained settings: the PERU MIGRANT Study.

AIM: To determine whether intermediate hyperglycaemia, defined by fasting plasma glucose and HbA1c criteria, is associated with mortality in a 10-year cohort of people in a Latin American country. METHODS: Analysis of the PERU MIGRANT Study was conducted in three different population groups (rural, rural-to-urban migrant, and urban). The baseline assessment was conducted in 2007/2008, with follow-up assessment in 2018. The outcome was all-cause mortality, and the exposure was intermediate hyperglycaemia, using three definitions: (1) impaired fasting glucose, defined according to American Diabetes Association criteria [fasting plasma glucose 5.6-6.9 mmol/l (100-125 mg/dl)]; (2) intermediate hyperglycaemia defined according to American Diabetes Association criteria [HbA1c levels 39-46 mmol/mol (5.7-6.4%)]; and (3) intermediate hyperglycaemia defined according to the International Expert Committee criteria [HbA1c levels 42-46 mmol/mol (6.0-6.4%)]. Crude and adjusted hazard ratios and 95% CIs were estimated using Cox proportional hazard models. RESULTS: At baseline, the mean (sd) age of the study population was 47.8 (11.9) years and 52.5% of the cohort were women. The study cohort was divided into population groups as follows: 207 people (20.0%) in the rural population group, 583 (59.7%) in the rural-to-urban migrant group and 198 (20.3%) in the urban population group. The prevalence of intermediate hyperglycaemia was: 6%, 12.9% and 38.5% according to the American Diabetes Association impaired fasting glucose definition, the International Expert Committee HbA1c -based definition and the American Diabetes Association HbA1c -based definition, respectively, and the mortality rate after 10 years was 63/976 (7%). Intermediate hyperglycaemia was associated with all-cause mortality using the HbA1c -based definitions in the crude models [hazard ratios 2.82 (95% CI 1.59-4.99) according to the American Diabetes Association and 2.92 (95% CI 1.62-5.28) according to the International Expert Committee], whereas American Diabetes Association-defined impaired fasting glucose was not [hazard ratio 0.84 (95% CI 0.26-2.68)]. In the adjusted model, however, only the American Diabetes Association HbA1c -based definition was associated with all-cause mortality [hazard ratio 1.91 (95% CI 1.03-3.53)], whereas the International Expert Committee HbA1c -based and American Diabetes Association impaired fasting glucose-based definitions were not [hazard ratios 1.42 (95% CI 0.75-2.68) and 1.09 (95% CI 0.33-3.63), respectively]. CONCLUSIONS: Intermediate hyperglycaemia defined using the American Diabetes Association HbA1c criteria was associated with an elevated mortality rate after 10 years in a cohort from Peru. HbA1c appears to be a factor associated with mortality in this Peruvian population

Characterizing blood metabolomics profiles associated with self-reported food intakes in female twins

Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: P<0.05; targeted: same direction) in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6), overall consisting of 106 different metabolites (74 known and 32 unknown), including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17), ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22), and three potential markers of fruit consumption (top association: apple and pears): including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8) and indolepropionate (0.026[0.004]; P = 2.39x10-9), and threitol (0.033[0.003]; P = 1.69x10-21). With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the DietMetab database (http://www.twinsuk.ac.uk/dietmetab-data/), an online tool to investigate our top associations

Workflow in Clinical Trial Sites & Its Association with Near Miss Events for Data Quality: Ethnographic, Workflow & Systems Simulation

10.1371/journal.pone.0039671PLoS ONE76

Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey

There is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients