Longitudinal associations of fundamental movement skills with objectively measured physical activity and sedentariness during school transition from primary to lower secondary school

Objectives

This study aimed to investigate cross-lagged associations of leaping skill and throwing–catching skills with objectively measured moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) during school transition from upper primary (Grade 6) to lower secondary school (Grade 7).

Glycemic Variability and CNS Inflammation: Reviewing the Connection

Glucose is the primary energy source for the brain, and exposure to both high and low levels of glucose has been associated with numerous adverse central nervous system (CNS) outcomes. While a large body of work has highlighted the impact of hyperglycemia on peripheral and central measures of oxidative stress, cognitive deficits, and vascular complications in Type 1 and Type 2 diabetes, there is growing evidence that glycemic variability significantly drives increased oxidative stress, leading to neuroinflammation and cognitive dysfunction. In this review, the latest data on the impact of glycemic variability on brain function and neuroinflammation will be presented. Because high levels of oxidative stress have been linked to dysfunction of the blood–brain barrier (BBB), special emphasis will be placed on studies investigating the impact of glycemic variability on endothelial and vascular inflammation. The latest clinical and preclinical/in vitro data will be reviewed, and clinical/therapeutic implications will be discussed.     

The facilitating factors and barriers influencing change in dental practice in a sample of English general dental practitioners

AIM: The objective of this study was to investigate the barriers and facilitators to change in dental practices among a sample of general dental practitioners (GDPs) from three regions of England. METHOD: In-depth face-to-face interviews with 60 GDPs were undertaken. The sample was selected from a group of 317 GDPs who had completed a questionnaire in the first phase of this study. The participants were selected to reflect diversity regarding the number and extent of self-reported changes reported in the questionnaire, and personal and practice characteristics. Of the 92 attempted contacts, 60 (65%) of the interviews were successfully completed. The interview schedule formed the basis of the interview. All the interviews and notes were transferred on to NUD*IST QSR version 4, a qualitative analysis package. RESULTS: No single factor was identified as being more important than another in facilitating change. The main facilitators for change were: financial factors, regular patient attendance, particularly a core patient group, staff loyalty, having regular staff meetings and open communication and having access to peer support. The main barriers to change were the reverse of the facilitators plus not having a financial stakehold in the practice. CONCLUSIONS: A range of factors were identified as influencing change in general dental practice. These include GDPs' attitudes and experience of change, patient factors, organisational issues, contact with peers and access to appropriate training courses.     

Do current therapeutic anti-Aβ antibodies for Alzheimer’s disease engage the target?

Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer’s disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target Aβ in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind Aβ with high affinity. All of the antibodies were able to bind Aβ in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated Aβ species, the Aβ detected using solanezumab was barely above detection limits while crenezumab did not detect any Aβ. None of the antibodies were able to detect any Aβ species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-Aβ related proteins. Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.