Off-axis Neuromuscular Training for Knee Ligament Injury Prevention and Rehabilitation

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Epitope mapping and fine specificity of human T and B cell responses for novel candidate blood-stage malaria vaccine P27A

P27A is a novel synthetic malaria vaccine candidate derived from the blood stage Plasmodium falciparum protein Trophozoite Exported Protein 1 (TEX1/PFF0165c). In phase 1a/1b clinical trials in malaria unexposed adults in Switzerland and in malaria pre-exposed adults in Tanzania, P27A formulated with Alhydrogel and GLA-SE adjuvants induced antigen-specific antibodies and T-cell activity. The GLA-SE adjuvant induced significantly stronger humoral responses than the Alhydrogel adjuvant. Groups of pre-exposed and unexposed subjects received identical vaccine formulations, which supported the comparison of the cellular and humoral response to P27A in terms of fine specificity and affinity for populations and adjuvants. Globally, fine specificity of the T and B cell responses exhibited preferred recognized sequences and did not highlight major differences between adjuvants or populations. Affinity of anti-P27A antibodies was around 10−8 M in all groups. Pre-exposed volunteers presented anti-P27A with higher affinity than unexposed volunteers. Increasing the dose of GLA-SE from 2.5 to 5 μg in pre-exposed volunteers improved anti-P27A affinity and decreased the number of recognized epitopes. These results indicate a higher maturation of the humoral response in pre-exposed volunteers, particularly when immunized with P27A formulated with 5 μg GLA-SE

4D Flow cardiovascular magnetic resonance consensus statement: 2023 update

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 '4D Flow CMR Consensus Statement'. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards

T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades

Pivoting neuromuscular control and proprioception in females and males

Noncontact ACL injuries occur most commonly in pivoting sports and are much more frequent in females than in males. However, information on sex differences in proprioceptive acuity under weight-bearing and leg neuromuscular control in pivoting is scarce. The objective of this study was to investigate sex differences in pivoting neuromuscular control during strenuous stepping tasks and proprioceptive acuity under weight-bearing. 21 male and 22 female subjects were recruited to evaluate pivoting proprioceptive acuity under weight-bearing, and pivoting neuromuscular control (in terms of leg pivoting instability, stiffness, maximum internal and external pivoting angles, and entropy of time-to-peak EMG in lower limb muscles) during strenuous stepping tasks performed on a novel offaxis elliptical trainer. Compared to males, females had significantly lower proprioceptive acuity under weight-bearing in both internal and external pivoting directions, higher pivoting instability, larger maximum internal pivoting angle, lower leg pivoting stiffness, and higher entropy of time-to-peak EMG in the gastrocnemius muscles during strenuous stepping tasks with internal and external pivoting perturbations. Results of this study may help us better understand factors contributing to ACL injuries in females and males, develop training strategies to improve pivoting neuromuscular control and proprioceptive acuity, and potentially reduce ACL and lower-limb musculoskeletal injuriesclose0

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Excel file describing body mass, oxidative stress and telomere dynamics of chicks after the winter tim

Catching-up but telomere loss: half-opening the black box of growth and ageing trade-off in wild king penguin chicks

One of the reasons for animals not to grow as fast as they potentially could is that fast growth has been shown to be associated with reduced lifespan. However, we are still lacking a clear description of the reality of growth-dependent modulation of ageing mechanisms in wild animals. Using the particular growth trajectory of small king penguin chicks naturally exhibiting higher-than-normal growth rate to compensate for the winter break, we tested whether oxidative stress and telomere shortening are related to growth trajectories. Plasma antioxidant defences, oxidative damage levels and telomere length were measured at the beginning and at the end of the post-winter growth period in three groups of chicks (small chicks, which either passed away or survived the growth period, and large chicks). Small chicks that died early during the growth period had the highest level of oxidative damage and the shortest telomere lengths prior to death. Here, we show that small chicks that grew faster did it at the detriment of body maintenance mechanisms as shown by (i) higher oxidative damage and (ii) accelerated telomere loss. Our study provides the first evidence for a mechanistic link between growth and ageing rates under natural conditions