Simulation-based evaluation of SAR and flip angle homogeneity for five transmit head arrays at 14 T.

INTRODUCTION: Various research sites are pursuing 14 T MRI systems. However, both local SAR and RF transmit field inhomogeneity will increase. The aim of this simulation study is to investigate the trade-offs between peak local SAR and flip angle uniformity for five transmit coil array designs at 14 T in comparison to 7 T. METHODS: Investigated coil array designs are: 8 dipole antennas (8D), 16 dipole antennas (16D), 8 loop coils (8D), 16 loop coils (16L), 8 dipoles/8 loop coils (8D8L) and for reference 8 dipoles at 7 T. Both RF shimming and kT-points were investigated by plotting L-curves of peak SAR levels vs flip angle homogeneity. RESULTS: For RF shimming, the 16L array performs best. For kT-points, superior flip angle homogeneity is achieved at the expense of more power deposition, and the dipole arrays outperform the loop coil arrays. DISCUSSION AND CONCLUSION: For most arrays and regular imaging, the constraint on head SAR is reached before constraints on peak local SAR are violated. Furthermore, the different drive vectors in kT-points alleviate strong peaks in local SAR. Flip angle inhomogeneity can be alleviated by kT-points at the expense of larger power deposition. For kT-points, the dipole arrays seem to outperform loop coil arrays.

A local multi-transmit coil combined with a high-density receive array for cerebellar fMRI at 7 T.

The human cerebellum is involved in a wide array of functions, ranging from motor control to cognitive control, and as such is of great neuroscientific interest. However, its function is underexplored in vivo, due to its small size, its dense structure and its placement at the bottom of the brain, where transmit and receive fields are suboptimal. In this study, we combined two dense coil arrays of 16 small surface receive elements each with a transmit array of three antenna elements to improve BOLD sensitivity in the human cerebellum at 7 T. Our results showed improved B1+ and SNR close to the surface as well as g-factor gains compared with a commercial coil designed for whole-head imaging. This resulted in improved signal stability and large gains in the spatial extent of the activation close to the surface (<3.5 cm), while good performance was retained deeper in the cerebellum. Modulating the phase of the transmit elements of the head coil to constructively interfere in the cerebellum improved the B1+ , resulting in a temporal SNR gain. Overall, our results show that a dedicated transmit array along with the SNR gains of surface coil arrays can improve cerebellar imaging, at the cost of a decreased field of view and increased signal inhomogeneity.

Can 7T MPRAGE match MP2RAGE for gray-white matter contrast?

Ultra-High Field (UHF) MRI provides a significant increase in Signal-to-Noise Ratio (SNR) and gains in contrast weighting in several functional and structural acquisitions. Unfortunately, an increase in field strength also induces non-uniformities in the transmit field (B1+) that can compromise image contrast non-uniformly. The MPRAGE is one of the most common T1 weighted (T1w) image acquisitions for structural imaging. It provides excellent contrast between gray and white matter and is widely used for brain segmentation. At 7T, the signal non-uniformities tend to complicate this and therefore, the self-bias-field corrected MP2RAGE is often used there. In both MPRAGE and MP2RAGE, more homogeneous image contrast can be achieved with adiabatic pulses, like the TR-FOCI inversion pulse, or special pulse design on parallel transmission systems, like Universal Pulses (UP). In the present study, we investigate different strategies to improve the bias-field for MPRAGE at 7T, comparing the contrast and GM/WM segmentability against MP2RAGE. The higher temporal efficiency of MPRAGE combined with the potential of the user-friendly UPs was the primary motivation for this MPRAGE-MP2RAGE comparison. We acquired MPRAGE data in six volunteers, adding a k-space shutter to reduce scan time, a kt-point UP approach for homogeneous signal excitation, and a TR-FOCI pulse for homogeneous inversion. Our results show remarkable signal contrast improvement throughout the brain, including regions of low B1+ such as the cerebellum. The improvements in the MPRAGE were largest following the introduction of the UPs. In addition to the CNR, both SNR and GM/WM segmentability were also assessed. Among the MPRAGEs, the combined strategy (UP + TR-FOCI) yielded highest SNR and showed highest spatial similarity between GM segments to the MP2RAGE. Interestingly, the distance between gray and white matter peaks in the intensity histograms did not increase, as better pulses and higher SNR especially benefitted the (cerebellar) gray matter. Overall, the gray-white matter contrast from MP2RAGE is higher, with higher CNR and higher intensity peak distances, even when scaled to scan time. Hence, the extra acquisition time for MP2RAGE is justified by the improved segmentability.

Sports injuries and illnesses at the Lausanne 2020 Youth Olympic Winter Games: a prospective study of 1783 athletes from 79 countries.

OBJECTIVE: To describe the injury and illness characteristics among participating athletes during the Lausanne 2020 Youth Olympic Winter Games (YOG 2020), 9-22 January 2020. METHODS: The daily number of athlete injuries and illnesses were recorded (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Lausanne 2020 medical staff. RESULTS: In total, 1783 athletes from 79 NOCs were observed. NOC and Lausanne 2020 medical staff reported 228 injuries and 167 illnesses, equating 11.7 injuries and 8.6 illnesses per 100 athletes over the 14-day period. Injury incidence was highest for snowboard slopestyle (39%), bobsleigh (36%), snowboard big air (29%), ski slopestyle (29%), snowboard cross (24%) and ski cross (21%), and lowest for speed skating, snowboard halfpipe and curling (2%-4%). The highest incidence of illness was recorded for curling (21%), ski mountaineering (15%), snowboard halfpipe (13%), bobsleigh (11%), cross-country skiing (10%) and figure skating (10%). Almost one-third of injuries were expected to result in time loss and 17% of illnesses. Most injuries occurred to the knee (12%) and head (11%), and 64% of illnesses affected the respiratory system. Overall, women suffered more injuries and illness than males. CONCLUSION: Overall, injury and illness rates were similar compared with recent YOG. While the rate and characteristics of injury and illness varied between sports, consistent patterns across YOG are emerging. If addressed, changes in highlighted areas of risk could have a positive impact on the health and well-being of these young athletes.

Genetic association research in football: A systematic review.

Genetic variation is responsible for a large amount of the inter-individual performance disparities seen in sport. As such, in the last ten years genetic association studies have become more common; with one of the most frequently researched sports being football. However, the progress and methodological rigour of genetic association research in football is yet to be evaluated. Therefore, the aim of this paper was to identify and evaluate all genetic association studies involving football players and outline where and how future research should be directed. Firstly, a systematic search was conducted in the Pubmed and SPORTDiscus databases, which identified 80 eligible studies. Progression analysis revealed that 103 distinct genes have been investigated across multiple disciplines; however, research has predominately focused on the association of the ACTN3 or ACE gene. Furthermore, 55% of the total studies have been published within the last four years; showcasing that genetic association research in football is increasing at a substantial rate. However, there are several methodological inconsistencies which hinder research implications, such as; inadequate description or omission of ethnicity and on-field positions. Furthermore, there is a limited amount of research on several key areas crucial to footballing performance, in particular; psychological related traits. Moving forward, improved research designs, larger sample sizes, and the utilisation of genome-wide and polygenic profiling approaches are recommended. Finally, we introduce the Football Gene Project, which aims to address several of these limitations and ultimately facilitate greater individualised athlete development within football.

The association of the ACTN3 R577X and ACE I/D polymorphisms with athlete status in football: a systematic review and meta-analysis.

The aim of this review was to assess the association of ACTN3 R577X and ACE I/D polymorphisms with athlete status in football and determine which allele and/or genotypes are most likely to influence this phenotype via a meta-analysis. A comprehensive search identified 17 ACTN3 and 19 ACE studies. Significant associations were shown between the presence of the ACTN3 R allele and professional footballer status (OR = 1.35, 95% CI: 1.18-1.53) and the ACE D allele and youth footballers (OR = 1.18, 95% CI: 1.01-1.38). More specifically, the ACTN3 RR genotype (OR = 1.48, 95% CI: 1.23-1.77) and ACE DD genotype (OR = 1.29, 95% CI: 1.02-1.63) exhibited the strongest associations, respectively. These findings may be explained by the association of the ACTN3 RR genotype and ACE DD genotype with power-orientated phenotypes and the relative contribution of power-orientated phenotypes to success in football. As such, the results of this review provide further evidence that individual genetic variation may contribute towards athlete status and can differentiate athletes of different competitive playing statuses in a homogenous team-sport cohort. Moreover, the ACTN3 R577X and ACE I/D polymorphisms are likely (albeit relatively minor) contributing factors that influence athlete status in football.

Is testosterone responsible for athletic success in female athletes?

BACKGROUND: The aim of this study was to determine the interrelationship between the resting serum testosterone (T) levels of female athletes from different types of sporting events and their athletic success. METHODS: The study involved 599 Russian international-level female athletes (95 highly elite, 190 elite, and 314 sub-elite; age: 16-35 years) and 298 age-matched female controls. The athlete cohort was stratified into four groups according to event duration, distance, and type of activity: 1) endurance athletes; 2) athletes with mixed activity; 3) speed/strength athletes; 4) sprinters. Athletic success was measured by determining the level of achievement of each athlete. RESULTS: The mean T levels of athletes and controls were 1.65±0.87 and 1.76±0.6 nmol/L (P=0.057 for difference between groups) with ranges of 0.08-5.82 and 0.38-2.83 nmol/L in athletes and controls, respectively. T levels were positively associated with athletic success in sprinters (P=0.0002 adjusted for age) only. Moreover, none of the sub-elite sprinters had T>1.9 nmol/L, while 50% of elite and highly elite sprinters had T>1.9 nmol/L (OR=47.0; P<0.0001). CONCLUSIONS: Our data suggest that the measurement of the serum T levels significantly correlates with athletic success in sprinters but not other types of athletes and in the future may be useful in the prediction of sprinting ability.

Milk processing increases the allergenicity of cow's milk-Preclinical evidence supported by a human proof-of-concept provocation pilot.

BACKGROUND: Several studies demonstrated the adverse effect of milk processing on the allergy-protective capacity of raw cow's milk. Whether milk processing also affects the allergenicity of raw milk is hardly investigated. OBJECTIVE: To assess the allergenicity of raw (unprocessed) and processed cow's milk in a murine model for food allergy as well as in cow's milk allergic children. METHODS: C3H/HeOuJ mice were either sensitized to whole milk (raw cow's milk, heated raw cow's milk or shop milk [store-bought milk]) and challenged with cow's milk protein or they were sensitized and challenged to whey proteins (native or heated). Acute allergic symptoms, mast cell degranulation, allergen-specific IgE levels and cytokine concentrations were determined upon challenge. Cow's milk allergic children were tested in an oral provocation pilot with organic raw and conventional shop milk. RESULTS: Mice sensitized to raw milk showed fewer acute allergic symptoms upon intradermal challenge than mice sensitized to processed milk. The acute allergic skin response was low (103 ± 8.5 µm vs 195 ± 17.7 µm for heated raw milk, P < 0.0001 and vs 149 ± 13.6 µm for shop milk, P = 0.0316), and there were no anaphylactic shock symptoms and no anaphylactic shock-induced drop in body temperature. Moreover, allergen-specific IgE levels and Th2 cytokines were significantly lower in raw milk sensitized mice. Interestingly, the reduced sensitizing capacity was preserved in the isolated native whey protein fraction of raw milk. Besides, native whey protein challenge diminished allergic symptoms in mice sensitized to heated whey proteins. In an oral provocation pilot, cow's milk allergic children tolerated raw milk up to 50 mL, whereas they only tolerated 8.6 ± 5.3 mL shop milk (P = 0.0078). CONCLUSION AND CLINICAL RELEVANCE: This study demonstrates that raw (unprocessed) cow's milk and native whey proteins have a lower allergenicity than their processed counterparts. The preclinical evidence in combination with the human proof-of-concept provocation pilot provides evidence that milk processing negatively influences the allergenicity of milk.

Genome-wide association study identifies a locus associated with rotator cuff injury.

Rotator cuff tears are common, especially in the fifth and sixth decades of life, but can also occur in the competitive athlete. Genetic differences may contribute to overall injury risk. Identifying genetic loci associated with rotator cuff injury could shed light on the etiology of this injury. We performed a genome-wide association screen using publically available data from the Research Program in Genes, Environment and Health including 8,357 cases of rotator cuff injury and 94,622 controls. We found rs71404070 to show a genome-wide significant association with rotator cuff injury with p = 2.31x10-8 and an odds ratio of 1.25 per allele. This SNP is located next to cadherin8, which encodes a protein involved in cell adhesion. We also attempted to validate previous gene association studies that had reported a total of 18 SNPs showing a significant association with rotator cuff injury. However, none of the 18 SNPs were validated in our dataset. rs71404070 may be informative in explaining why some individuals are more susceptible to rotator cuff injury than others.

Two Genetic Loci associated with Medial Collateral Ligament Injury.

Medial collateral ligament (MCL) injuries are a common knee injury, especially in competitive athletes. Identifying genetic loci associated with MCL injury could shed light on its etiology. A genome-wide association screen was performed using data from the Research Program in Genes, Environment and Health (RPGEH) including 1 572 cases of MCL injury and 100 931 controls. 2 SNPs (rs80351309 and rs6083471) showed an association with MCL injury at genome-wide significance (p<5×10-8) with moderate effects (odds ratios=2.12 and 1.57, respectively). For rs80351309, the genotypes were imputed with only moderate accuracy, so this SNP should be viewed with caution until its association with MCL injury can be validated. The SNPs rs80351309 and rs6083471 show a statistically significant association with MCL injury. It will be important to replicate this finding in future studies.

Genome-wide association screens for Achilles tendon and ACL tears and tendinopathy.

Achilles tendinopathy or rupture and anterior cruciate ligament (ACL) rupture are substantial injuries affecting athletes, associated with delayed recovery or inability to return to competition. To identify genetic markers that might be used to predict risk for these injuries, we performed genome-wide association screens for these injuries using data from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort consisting of 102,979 individuals. We did not find any single nucleotide polymorphisms (SNPs) associated with either of these injuries with a p-value that was genome-wide significant (p<5x10-8). We found, however, four and three polymorphisms with p-values that were borderline significant (p<10-6) for Achilles tendon injury and ACL rupture, respectively. We then tested SNPs previously reported to be associated with either Achilles tendon injury or ACL rupture. None showed an association in our cohort with a false discovery rate of less than 5%. We obtained, however, moderate to weak evidence for replication in one case; specifically, rs4919510 in MIR608 had a p-value of 5.1x10-3 for association with Achilles tendon injury, corresponding to a 7% chance of false replication. Finally, we tested 2855 SNPs in 90 candidate genes for musculoskeletal injury, but did not find any that showed a significant association below a false discovery rate of 5%. We provide data containing summary statistics for the entire genome, which will be useful for future genetic studies on these injuries.

Correction: Applying Personal Genetic Data to Injury Risk Assessment in Athletes.

[This corrects the article DOI: 10.1371/journal.pone.0122676.].

Applying personal genetic data to injury risk assessment in athletes.

Recent studies have identified genetic markers associated with risk for certain sports-related injuries and performance-related conditions, with the hope that these markers could be used by individual athletes to personalize their training and diet regimens. We found that we could greatly expand the knowledge base of sports genetic information by using published data originally found in health and disease studies. For example, the results from large genome-wide association studies for low bone mineral density in elderly women can be re-purposed for low bone mineral density in young endurance athletes. In total, we found 124 single-nucleotide polymorphisms associated with: anterior cruciate ligament tear, Achilles tendon injury, low bone mineral density and stress fracture, osteoarthritis, vitamin/mineral deficiencies, and sickle cell trait. Of these single nucleotide polymorphisms, 91% have not previously been used in sports genetics. We conducted a pilot program on fourteen triathletes using this expanded knowledge base of genetic variants associated with sports injury. These athletes were genotyped and educated about how their individual genetic make-up affected their personal risk profile during an hour-long personal consultation. Overall, participants were favorable of the program, found it informative, and most acted upon their genetic results. This pilot program shows that recent genetic research provides valuable information to help reduce sports injuries and to optimize nutrition. There are many genetic studies for health and disease that can be mined to provide useful information to athletes about their individual risk for relevant injuries.

Cellular strategies of protein quality control.

Eukaryotic cells must contend with a continuous stream of misfolded proteins that compromise the cellular protein homeostasis balance and jeopardize cell viability. An elaborate network of molecular chaperones and protein degradation factors continually monitor and maintain the integrity of the proteome. Cellular protein quality control relies on three distinct yet interconnected strategies whereby misfolded proteins can either be refolded, degraded, or delivered to distinct quality control compartments that sequester potentially harmful misfolded species. Molecular chaperones play a critical role in determining the fate of misfolded proteins in the cell. Here, we discuss the spatial and temporal organization of cellular quality control strategies and their implications for human diseases linked to protein misfolding and aggregation.

Caffeic acid phenethyl ester inhibits PDGF-induced proliferation of vascular smooth muscle cells via activation of p38 MAPK, HIF-1α, and heme oxygenase-1.

Hyperproliferation of vascular smooth muscle cells (VSMCs) is critically involved in the onset of atherosclerosis and restenosis. Although caffeic acid phenethyl ester (CAPE, 1), one of the main constituents of honeybee propolis, has been shown to exert a beneficial effect in models of vascular injury in vivo, detailed mechanistic investigations in vascular cells are scarce. This study has examined the antiproliferative activity of 1 in platelet-derived growth factor (PDGF)-stimulated primary rat aortic VSMCs and aimed to shed light on underlying molecular mechanisms. Compound 1 inhibited the proliferation of VSMCs upon exposure to PDGF in a dose-dependent manner by interfering with cell cycle progression from the G0/1- to the S-phase. Enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) as well as stabilization of hypoxia-inducible factor (HIF)-1α and subsequent induction of heme oxygenase-1 (HO-1) could be identified as molecular events contributing to the observed growth arrest in PDGF-activated VSMCs upon exposure to 1.

Interpersonal coping among boys with ADHD.

OBJECTIVE: The authors investigate self-reported coping with interpersonal stressors among boys with and without ADHD in two studies and provide initial evidence for effects of different subgroups of ADHD on coping in Study 2. METHOD: In Study 1, 20 Austrian adolescents with ADHD were compared to 20 healthy controls. In Study 2, 44 German children and adolescents with ADHD (35 without and 9 with conduct disorders) were compared to 44 healthy controls matched by age and grade level, respectively. RESULTS: Increased maladaptive coping was found in both studies. Study 2 revealed heightened maladaptive coping among both subgroups of ADHD, but the subgroup of ADHD with conduct disorders was more affected compared to healthy controls than the subgroup with ADHD alone. CONCLUSION: Results suggest an impaired interpersonal coping style in ADHD and point to the potential benefit of stress management and social skills training for boys with ADHD. (

Resveratrol inhibits angiotensin II- and epidermal growth factor-mediated Akt activation: role of Gab1 and Shp2.

trans-Resveratrol (RV), a polyphenolic stilbene derivative found in grape skin and other food products, has been proposed to exert beneficial effects in cardiovascular disease. Our group has shown previously that RV inhibits angiotensin II (Ang II)-induced Akt activation and, consequently, vascular smooth muscle cell (VSMC) hypertrophy. In this work, to identify the molecular target of RV, we investigated the impact of RV on early signaling cascades in rat aortic VSMCs triggered by Ang II and epidermal growth factor (EGF). We show that RV does not influence Ang II-mediated transactivation of EGF-receptor but potently inhibits EGF-induced phosphorylation of Akt kinase, suggesting that RV acts downstream of EGF-receptor transactivation in VSMCs. Recent evidence indicates that the adapter molecule Gab1, together with the protein tyrosine phosphatase Shp2, is critically involved in regulating the strength and duration of phosphatidylinositol-3-kinase (PI3K) and Akt activation upon EGF stimulation in fibroblasts. Our results show that stimulation of VSMCs with EGF as well as Ang II leads to a rapid tyrosine phosphorylation of Gab1 and its association with the p85 subunit of PI3K. RV attenuates these processes. Experiments performed in Shp2-deficient fibroblasts revealed that RV does not inhibit EGF-stimulated Akt activation in these cells, suggesting that Shp2 is necessary for the inhibitory effect of RV on the PI3K/Akt pathway. Furthermore, RV treatment activates Shp2. We therefore propose that RV blocks Akt activation in Ang II- and EGF-stimulated VSMCs by activating Shp2, thus preventing interaction between Gab1 and PI3K that is necessary for further signal transduction.

Recent advances in treatment strategies for atopic dermatitis.

A wide range of different therapeutic regimens are used for atopic dermatitis. Although many treatment modalities are well established worldwide among clinicians, only the minority of these therapy recommendations are based on results of randomised controlled trials (RCTs). To close the gap between such 'generally' recommended therapies and therapies that are based on data from controlled trials, this review focuses not only on the pharmacological and clinical aspects of the currently proven agents, but also on the advantages and disadvantages of therapies that have not yet been completely tested.A review of the available literature concerning the pharmacological profile and also the level of evidence of therapeutic efficacy of all currently known topical and systemic agents for the treatment of atopic dermatitis reveals a large gap between the knowledge concerning the pharmacological action in vitro and the evidence of clinical efficacy in many cases. We agree with the conclusion of previous reviews that numerous therapies for atopic dermatitis urgently require more independent RCTs and especially comparative trials (e.g. corticosteroids vs calcineurin inhibitors). These are required in order to facilitate the choice of therapeutic strategy for the individual treatment of atopic dermatitis, with its broad spectrum of clinical manifestations and potential complications in adult patients and, particularly, in children.Finally, we also review preclinical trials with several new drugs. Immunomodulators appear to promise a new dimension for the future of therapy for atopic dermatitis, especially for severe and otherwise refractory forms or as alternatives to corticosteroids, that is, to treat facial atopic eczema without the risk of adverse effects.