Efficacy,safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended for glycaemic management in patients with type 2 diabetes (T2D). Oral semaglutide, the first oral GLP-1RA, has recently been approved for clinical use, based on the results of the randomized, Phase 3a Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) clinical trials. The PIONEER programme tested oral semaglutide in patients with T2D of duration ranging from 3.5 to 15 years, from monotherapy through to insulin add-on, in global populations and two trials dedicated to Japanese patients. Outcomes (glycated haemoglobin [HbA1c] and body weight reduction, plus other relevant efficacy and safety endpoints) were tested against both placebo and active standard-of-care medications. A separate trial evaluated the cardiovascular safety of oral semaglutide in patients with T2D at high cardiovascular risk. Over periods of treatment up to 78 weeks, oral semaglutide 7 and 14 mg once daily reduced HbA1c and body weight across the spectrum of T2D, and improved other diabetes-related endpoints, such as fasting plasma glucose. Oral semaglutide provided significantly better efficacy than placebo and commonly used glucose-lowering medications from the dipeptidyl peptidase-4 inhibitor (sitagliptin) and sodium-glucose co-transporter-2 inhibitor (empagliflozin) classes, as well as the subcutaneous GLP-1RAs liraglutide and dulaglutide. Oral semaglutide was well tolerated in line with the known safety profile of GLP-1RAs, with transient gastrointestinal events being the most common side effects reported. Cardiovascular safety was demonstrated for oral semaglutide in patients with cardiovascular disease or high cardiovascular risk. The results of the PIONEER programme suggest that oral semaglutide is efficacious and well tolerated for glycaemic control of T2D. The availability of oral semaglutide may help to broaden treatment choice and facilitate adoption of earlier GLP-1RA treatment in the paradigm of T2D management.     

Flanker interference effects in a line bisection task

Previous studies have shown that flanking distractors influence line bisection. In the present study, we examined if reaching the flanker after bisecting the line resulted in a variation of flanker interference on line bisection. Right- and left-handed participants were asked to bisect a horizontal line flanked by a dot (bisection task, B-task) or to bisect the line and then to reach the dot (bisection plus reaching task, BR-task). The dot was placed laterally to, and above or below, the line edge. The results showed that in both tasks the subjective midpoint was shifted away from the position of the dot. However, this effect was greater in the BR-task than in the B-task. We suggest that the requirement to perform an action to the flanker in the BR-task induced participants to pay more attention to the dot, enhancing its salience and distorting effects on line bisection.     

Innovation and Integrity: Desiderata and Future Directions for Prevention and Intervention Science

This article summarizes essential implications of the papers within this special issue and discusses directions for future prevention and intervention research on conceptual issues, methodological and transfer-related challenges and opportunities. We identify a need to move from programs to principles in intervention research and encourage the implementation of research on potential mechanisms underlying intervention effectiveness. In addition, current methodological issues in intervention research are highlighted, including advancements in methodology and statistical procedures, extended outcome assessments, replication studies, and a thorough examination of potential biases. We further discuss transfer-related issues, for example the need for more research on the flexibility and adaptability of programs and intervention approaches as well as more general problems in knowledge translation reasoning the need for enhanced communication between practitioners, policy makers, and researchers. Finally, we briefly touch on the need to discuss the relation between single intervention programs, the mental health system, and changes of contextual conditions at the macro level.     

Glycan-Based Near-infrared Fluorescent (NIRF) Imaging of Gastrointestinal Tumors: a Preclinical Proof-of-Concept In Vivo Study

Molecular Imaging and Biology - Aberrantly expressed glycans in cancer are of particular interest for tumor targeting. This proof-of-concept in vivo study aims to validate the use of aberrant Lewis...     

Use of Monoclonal Antibodies in the Sensitive Detection and Neutralization of Botulinum Neurotoxin Serotype B

Botulinum neurotoxins (BoNT) are some of nature’s most potent toxins. Due to potential food contamination, and bioterrorism concerns, the development of detection reagents, therapeutics and countermeasures are of urgent interest. Recently, we have developed a sensitive electrochemiluminescent (ECL) immunoassay for BoNT/B, using monoclonal antibodies (mAbs) MCS6-27 and anti-BoNT/B rabbit polyclonal antibodies as the capture and detector. The ECL assay detected as little as 1 pg/mL BoNT/B in the buffer matrix, surpassing the detection sensitivities of the gold standard mouse bioassays. The ECL assay also allowed detection of BoNT/B in sera matrices of up to 100% sera with negligible matrix effects. This highly-sensitive assay allowed the determination of the biological half-lives of BoNT/B holotoxin in vivo. We further tested the toxin neutralization potential of our monoclonal antibodies using the mouse systemic and oral intoxication models. A combination of mAbs protected mice in both pre- and post-exposure models to lethal doses of BoNT/B. MAbs were capable of increasing survival of animals when administered even 10 h post-intoxication in an oral model, suggesting a likely time for BoNT/B complexes to reach the blood stream. More sensitive detection assays and treatments against BoNT intoxication will greatly enhance efforts to combat botulism.     

Fading an Auditory Model by Volume to Teach Mands to Children with Autism Spectrum Disorder

The effectiveness of an audio model faded by volume on manding for materials was evaluated within an interrupted behavior chain with two children with autism. Behavior chains were interrupted to contrive an establishing operation (EO) by providing broken items and were interspersed with abolishing operation (AO) trials. An auditory model to teach mands was faded systematically by volume. Using a multiple probe design across three preferred activities, it was found that both participants were manded for some items in the absence of an audio prompt after it was faded systematically. Following the introduction of a prompt delay, participants learned to mand across remaining targets. Across participants, manding generalized to a novel interruption form (i.e., in sight but out of reach materials), to novel materials, and were maintained. Goals, procedures, and outcomes of the intervention were rated socially valid by clinicians.