Ligand-mediated transport of drug delivery devices across the blood-brain barrier

Hèt struikelblok voor succesvolle medicijnafgifte in de hersenen is de bloed-hersenbarrière (BBB). Promovenda Julia Georgieva bestudeerde hoe nanodeeltjes met daarin medicijnen ‘verpakt’, zich kunnen binden aan cellen van de BBB om vervolgens te worden getransporteerd. Georgieva concludeert dat GM1-receptorbindende nanodeeltjes een veelbelovend systeem is voor medicijnafgifte in de hersenen. Nanodeeltjes kunnen worden gebruikt als medicijnafgiftesysteem wanneer ze op hun oppervlak de juiste ‘targetingliganden’ dragen. Met deze liganden kunnen de deeltjes binden aan transportsystemen die stoffen in de hersenen brengen. Wanneer een medicijn is ingesloten in een nanodeeltje is het bovendien beschermd tegen afbraak tijdens het transport naar de hersenen. In dit project werden twee receptoren gekarakteriseerd met de potentie om receptor-gemedieerd transport van nanodeeltjes mogelijk te maken, waaronder monosialoganglioside (GM1). Door middel van faagdisplay werden nieuwe peptideliganden geïdentificeerd die kunnen binden aan GM1. Deze liganden werden op het oppervlak van nanodeeltjes gezet. De nanodeeltjes met een GM1-bindend ligand bleken in muizen naar de hersenen te worden getransporteerd. Zowel in vitro (in endotheelcelkweken) als in vivo toonden zij een hoge transportcapaciteit, wat leidde tot hun opname in de hersenen. Dit maakt deze GM1-bindende nanodeeltjes tot een veelbelovend systeem voor medicijnafgifte in de hersenen

Prediction and management of aircraft noise annoyance around Canadian airports

Noise pollution is a serious environmental problem affecting millions of people world-wide. Aircraft are one source of transportation noise that impacts residents in communities surrounding airports and flight paths. Noise is the biggest nuisance of airport operations and has resulted in complaints, protests, and even legal action. The burden of noise is likely to increase in the coming decades as quieter aircraft technologies lag traffic growth projections, and rapid urbanization narrows the buffer between airports and residential areas. Numerous physical and psychological effects of aircraft noise exposure have been studied, the most common of which is annoyance. Noise annoyance has been identified as a primary health effect endpoint of environmental noise exposure and has also been identified as an aggravating factor to other suspected health effect endpoints. Noise annoyance is also the primary metric used in aircraft noise regulations and guidelines that aim to reduce the effects of aircraft noise on individuals. Managing noise annoyance is the goal of most noise mitigation efforts. Failure to do so can result in prolonged conflicts between airports and their neighbours. To prevent severe annoyance, competent authorities across the world have taken initiative to study the phenomenon and improve methods for its prediction and management. This is a complex task due to the nature of noise annoyance, which does not strictly and closely correlate to noise exposure metrics. More insight into the non-stimulus-related variables, or non-acoustic factors, is required to effectively predict and mitigate annoyance. Acquiring this level of understanding requires large cross-sectional studies that revise and calibrate annoyance and noise metrics, noise thresholds, and guidelines as well as identify non-acoustic contributors to annoyance. Canada has not undertaken this initiative, often relying on international findings to inform its noise policy. This is problematic as annoyance trends evolve with time and location, thus the annoyance prediction and mitigation employed in one country or even community, may not be appropriate at another time and in a different setting. The goal of this research is to improve noise annoyance prediction and understanding, particularly in Canada, in order to facilitate for the management of community expectations. The original hypothesis implored the creation of new metrics that would better correlate to annoyance thus enhance its prediction. Following an extensive review of Canada’s current system for noise annoyance prediction, the Noise Exposure Forecast (NEF), it was determined that the NEF metric is adequate, yet its application and interpretation are flawed and outdated. As a result, the system fails to reflect true community response to noise at various noise exposure levels. To improve the understanding, prediction and ultimately mitigation of annoyance, this research conducted a thorough review of the NEF system including but not limited to noise and annoyance metrics, noise thresholds, noise contours and community response prediction guidelines. In addition, two community surveys were executed in the vicinity of Toronto Pearson International Airport to establish the prevalence of severe noise annoyance and by way of that create a regional dose-response relationship. The surveys also identified non-acoustic variables associated with annoyance. This work contributes to the modernization of Canadian state of the science relating to aircraft noise annoyance and sets the basis for further nationwide research. Resulting from this work was a comparative analysis between the NEF metric and other land use planning metrics (Lden, DNL), a regional dose-response relationship, an updated noise exposure threshold for the onset of significant annoyance, recommendations for revisions to the guidelines for the prediction of community response to aircraft noise, revised noise contour modelling method for the purpose of annoyance prediction, and a statistical model identifying acoustic and non-acoustic predictors of severe annoyance. The above discussed outcomes will provide an updated set of tools to be used in the prediction and management of aircraft noise annoyance around Canadian airports

Changes in intima media thickness, ankle brachial index and flow mediated dilation in pre hypertensive individuals

Introduction: Prehypertension (PH) is a state being on the frontier between the physiological referent arterial pressure values and pathological ones. The opinion concerned with its treatment is contradictory. Vascular alteration is an object of interest.Material and methods:  Intima Media Thickness (IMT), Ankle Brachial Index (ABI) and Flow Mediated Dilation (FMD) indices were examined in 103 individuals with PH and 45 normotensives. Anthropometric and clinical chemical methods were also applied. The statistical processing was carried out by ÐœS Excel 2000 and SPSS 11.0.Results: The pre hypertensives` metabolic profile was unfavorable, they are overweight and have bigger waist size, reflecting in higher cardiovascular risk. The percentage of FMD is reduced as an expression of endothelial function. Structural vascular alterations are not registered - ITM and ABI values are of no significant difference in the two followed up groups.Conclusion: The therapeutic approach in prehypertensives should be directed to reestablishment of the endothelial function.

Risk profile and hemodynamic characteristics in young subjects with high normal arterial blood pressure

Introduction: The European Society of Cardiology classifies arterial pressure bellow 140/90 mmHg as optimal (below 120/80 mmHg), normal (120-129 mmHg for systolic and/or 80-84 mmHg for diastolic) and high normal (130-139 mmHg for systolic and/or 85-89 mmHg for diastolic). The argument is concerned with different cardiovascular risk. The possibility for arterial hypertension (AH) to appear is higher in individuals with high normal arterial pressure (HNAP). Such individuals could be treated with non-drug therapy as the idea is the appearance of AH to be delayed and the cardiovascular risk to be reduced.The goal of the study was to examine the risk and hemodynamic profile of medical students with HNAP.Material and methods:  The object of the investigation was focused on medical students with HNAP. The two followed-up groups - with HNAP and with optimal arterial blood pressure (OBP) assumed this pattern on the base of inquiry and screening among 116 students (60 men and 56 women). Inquiry and anthropometric methods, arterial pressure monitoring and impedance cardiography were carried out.Results: The dominance of some factors, predisposing hypertension appearance as overweight, increased salt consumption, family history was registered in HNAP group. Hemodynamic evaluation manifested hyperkinetic type of circulation.Conclusion: Medical students` risk and hemodynamic profile within HNAP group is close to that of the hypertensive individuals. That makes them a special risk group and there is a necessity of non-drug treatment in order to delay AH expression

Effectiveness of mouth rinsing versus ingesting pickle juice for alleviating electrically induced cramp in physically active adults

(1) Background: Stimulating oropharyngeal transient receptor potential (TRP) channels in-hibits muscle cramping by triggering a supraspinal reflex to reduce α-motor neuron hyperexcitability. This study investigated whether the longer stimulation of the TRP channels via mouth rinsing with PJ is more effective than drinking PJ at inhibiting an electrically induced muscle cramp (EIMC). Both conditions were compared to the control (water). (2) Methods: The tibial nerves in 11 cramp-prone adults were percutaneously stimulated to elicit an EIMC of the flexor hallucis brevis in three trials that took place one week apart from each other. At cramp onset, the participants received mouth rinsing and expelling PJ (25 mL), ingesting PJ (1 mL·kg−1 body-mass (BM)), or ingesting water (1 mL·kg−1 BM). Cramp onset and offset were induced by electromyography, and the severity of discomfort was recorded using a visual analogue scale (VAS). (3) Results: The median time to cramp cessation as a percentage of water was 82.8 ± 14.63% and 68.6 ± 47.78% for PJ ingestion and PJ mouth rinsing, respectively. These results had large variability, and no statistically significant differences were observed. There were also no differences in perceived cramp discomfort between conditions, despite the hazard ratios for the time taken to reach VAS = 0, which was higher than water (control) for PJ ingestion (22%) and mouth rinsing (35%) (p = 0.66 and 0.51, respectively). (4) Conclusions: The data suggest no difference in cramp duration and perceived discomfort between PJ and water. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Andrew Lavender” is provided in this record*

Smuggling Drugs into the Brain:An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood-Brain Barrier

The blood–brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood–brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier–drug system (“Trojan horse complex”) is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain

Towards Active Learning for Action Spotting in Association Football Videos

Association football is a complex and dynamic sport, with numerous actions occurring simultaneously in each game. Analyzing football videos is challenging and requires identifying subtle and diverse spatio-temporal patterns. Despite recent advances in computer vision, current algorithms still face significant challenges when learning from limited annotated data, lowering their performance in detecting these patterns. In this paper, we propose an active learning framework that selects the most informative video samples to be annotated next, thus drastically reducing the annotation effort and accelerating the training of action spotting models to reach the highest accuracy at a faster pace. Our approach leverages the notion of uncertainty sampling to select the most challenging video clips to train on next, hastening the learning process of the algorithm. We demonstrate that our proposed active learning framework effectively reduces the required training data for accurate action spotting in football videos. We achieve similar performances for action spotting with NetVLAD++ on SoccerNet-v2, using only one-third of the dataset, indicating significant capabilities for reducing annotation time and improving data efficiency. We further validate our approach on two new datasets that focus on temporally localizing actions of headers and passes, proving its effectiveness across different action semantics in football. We believe our active learning framework for action spotting would support further applications of action spotting algorithms and accelerate annotation campaigns in the sports domain.Comment: Accepted at CVSports'2

Do Helpful Mothers Help? Effects of Maternal Scaffolding and Infant Engagement on Cognitive Performance.

Infants are highly social and much early learning takes place in a social context during interactions with caregivers. Previous research shows that social scaffolding - responsive parenting and joint attention - can confer benefits for infants' long-term development and learning. However, little previous research has examined whether dynamic (moment-to-moment) adaptations in adults' social scaffolding are able to produce immediate effects on infants' performance. Here we ask whether infants' success on an object search task is more strongly influenced by maternal behavior, including dynamic changes in response behavior, or by fluctuations in infants' own engagement levels. Thirty-five mother-infant dyads (infants aged 10.8 months, on average) participated in an object search task that was delivered in a naturalistic manner by the child's mother. Measures of maternal responsiveness (teaching duration; sensitivity) and infant engagement (engagement score; visual attention) were assessed. Mothers varied their task delivery trial by trial, but neither measure of maternal responsiveness significantly predicted infants' success in performing the search task. Rather, infants' own level of engagement was the sole significant predictor of accuracy. These results indicate that while parental scaffolding is offered spontaneously (and is undoubtedly crucial for development), in this context children's endogenous engagement proved to be a more powerful determinant of task success. Future work should explore this interplay between parental and child-internal factors in other learning and social contexts