Median and range of DMSO controls from LPS-stimulated PBMCs (n = 6 cultures in duplicates).

<p>Median and range of DMSO controls from LPS-stimulated PBMCs (n = 6 cultures in duplicates).</p

PBDE measurements in stock solution, culture media and cells, mean of double determinations.

<p>PBDE measurements in stock solution, culture media and cells, mean of double determinations.</p

Influence of DE-71 on cytokine responses of PBMCs.

<p>Mean + SD of secretion of TNF-α, IFN-γ, IL-17A, and IL-17F from DE-71 exposed and PHA-L-stimulated PBMCs are shown as ratios to the respective DMSO controls. The red dotted line indicates the level of the DMSO controls (ratio = 1). * = p<0.05 compared to DMSO control, # = p<0.05 compared to 0.01 μg/mL DE-71, + = p<0.05 compared to 0.1 μg/mL DE-71, ¤ = p<0.05 compared to 1 μg/mL DE-71. PBMC: peripheral mononuclear cells, PHA-L: phytohemagglutinin-L, TNF-α: tumor necrosis factor-α, IFN-γ: interferon-γ, IL-17A: interleukin-17a, IL-17F: interleukin-17F DMSO = dimethyl sulfoxide, SD = standard deviation.</p

Mean of LDH-fluorescence from DE-71 exposed and PHA-L-stimulated PBMCs.

<p>DE-71 was added in six different concentrations to each culture, medium and DMSO in medium served as negative controls in duplicate, n = 2 cultures in triplicates. LDH: lactate dehydrogenase, PHA-L: phytohemagglutinin-L, DMSO: dimethyl sulfoxid, RFU: relative fluorescence unit.</p

Median and range of DMSO controls from PHA-L-stimulated PBMCs (n = 6 cultures in duplicates).

<p>Median and range of DMSO controls from PHA-L-stimulated PBMCs (n = 6 cultures in duplicates).</p

Mean of LDH-fluorescence from DE-71 exposed and LPS-stimulated PBMCs.

<p>DE-71 was added in six different concentrations to each culture and medium, and DMSO in medium served as negative controls in duplicate, n = 2 cultures in triplicates. LDH: lactate dehydrogenase, LPS: lipopolysaccharide, DMSO: dimethyl sulfoxid, RFU: relative fluorescence unit.</p

Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5) : A Randomized Trial.

BackgroundInadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden.ObjectiveTo compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice.Design52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626).Setting176 sites in 7 countries.Participants1085 insulin-naive adults with T2D.InterventionIcodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300).MeasurementsThe primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score).ResultsThe estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments.LimitationInability to differentiate the effects of icodec and the dosing guide app.ConclusionCompared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates.Primary funding sourceNovo Nordisk A/S

Concentrations of DE-71 in supernatants and cells.

<p>Measured concentration of PBDE congeners (μg/L) in cells and supernatants in comparison to added concentrations of DE-71. <i>LOD</i>: <i>Limit of detection</i>.</p

Influence of the flame retardant DE-71 on thyroid specific gene expression.

<p>Cultures of human thyrocytes were stimulated with 1 IU/TSH and in absence or presence of DE-71, at different concentrations. After 72 hours, expression of thyroglobulin (Tg), thyroid stimulated hormone receptor (TSHr), thyroid peroxidase (TPO), interleukin-6 (IL-6) and sodium iodide symporter (NIS) genes were measured by RT-qPCR. Shown are mean+SD of the ratio of quantified mRNA normalized to housekeeping gene to the negative control (control = 1; dotted line) for five experiments. *p<0.05 for the null-hypothesis that DE-71 had no effect.</p

Sequences of the primers used in RT-qPCR.

<p>Sequences of the primers used in RT-qPCR.</p