Mechanical properties of human tumour tissues and their implications for cancer development.

The mechanical properties of cells and tissues help determine their architecture, composition and function. Alterations to these properties are associated with many diseases, including cancer. Tensional, compressive, adhesive, elastic and viscous properties of individual cells and multicellular tissues are mostly regulated by reorganization of the actomyosin and microtubule cytoskeletons and extracellular glycocalyx, which in turn drive many pathophysiological processes, including cancer progression. This Review provides an in-depth collection of quantitative data on diverse mechanical properties of living human cancer cells and tissues. Additionally, the implications of mechanical property changes for cancer development are discussed. An increased knowledge of the mechanical properties of the tumour microenvironment, as collected using biomechanical approaches capable of multi-timescale and multiparametric analyses, will provide a better understanding of the complex mechanical determinants of cancer organization and progression. This information can lead to a further understanding of resistance mechanisms to chemotherapies and immunotherapies and the metastatic cascade.

Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin.

The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering differential mechanoresponses. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has a stronger contribution than Arp2/3 to both traction and actin flow. Intriguingly, despite only slight changes in F-actin flow speed observed in cells with the combined inhibition of Arp2/3 and myosin compared to cells with sole myosin inhibition, they show a 4-times reduction in traction than cells with myosin-only inhibition. Our analyses indicate that traditional models based on rigid F-actin are inadequate for capturing such dramatic force reduction with similar actin flow. Instead, incorporating the F-actin network's viscoelastic properties is crucial. Our new model including the F-actin viscoelasticity reveals that Arp2/3 and formin enhance stiffness sensitivity by mechanically reinforcing the F-actin network, thereby facilitating more effective transmission of flow-induced forces. This model is validated by cell stiffness measurement with atomic force microscopy and experimental observation of model-predicted stiffness-dependent actin flow fluctuation.

Knee Cartilage Injuries in Football Players: Clinical Outcomes and Return to Sport After Surgical Treatment: A Systematic Review of the Literature.

OBJECTIVE: To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players. DESIGN: A systematic literature review was performed in August 2023 on PubMed, WebOfScience, and Cochrane Library to collect studies on surgical strategies for cartilage lesions in football players. Methodological quality and risk of bias were assessed with the modified Coleman Methodology score and RoB2 and RoBANS2 tools. RESULTS: Fifteen studies on 409 football players (86% men, 14% women) were included: nine prospective and two retrospective case series, one randomized controlled trial, one prospective comparative study, one case report, and one survey. Bone marrow stimulation (BMS) techniques were the most documented. The lesion size influenced the treatment choice: debridement was used for small lesions (1.1 cm2), BMS, osteochondral autograft transplantation (OAT), matrix-assisted autologous chondrocytes transplantation (MACT), and scaffold-augmented BMS for small/mid-size lesions (2.2-3.0 cm2), and autologous chondrocytes implantation (ACI) for larger lesions (5.8 cm2). The surgical options yielded different results in terms of clinical outcome and return-to-sport, with fastest recovery for debridement and scaffold-augmented BMS. The current evidence is limited with large methodological quality variation (modified Coleman Methodology score 43.5/100) and a high risk of bias. CONCLUSIONS: Decision-making in cartilage injuries seems to privilege early return-to-sport, making debridement and microfractures the most used techniques. The lesion size influences the treatment choice. However, the current evidence is limited. Further studies are needed to confirm these findings and establish a case-based approach to treat cartilage injuries in football players based on the specific patient and lesion characteristics and the treatments' potential in terms of both return-to-sport and long-term results. LEVEL OF EVIDENCE: Systematic review, level IV.

Evaluation of a medical after-care intervention among deselected elite male Academy football players: a pilot study.

Objective: This pilot study aimed to evaluate the perception and satisfaction of deselected male Academy professional footballers towards a medical after-care intervention. Methods: A quasiexperimental study design, with deselected players (aged≥18 years) at a single Premier League Academy during the 2022/2023 season, were invited to participate. The intervention included individualised health recommendations, key medical information and signposting to key support resources. Participants' perceptions and satisfaction were assessed through an electronic survey. Descriptive analyses (mean, SD, frequency and/or range) were performed for all variables. Results: Twelve out of 15 eligible participants (80% response rate) provided informed consent and completed the survey (mean age: 19.5 years). All (100%) of the participants were satisfied with receiving the medical information. Ten out of 12 (83.3%) participants agreed that all Academy players should receive this medical intervention on deselection. Nine (75%) players felt more prepared for the next steps in their careers due to the medical information shared with them. Conclusion: Deselected male Academy footballers expressed high satisfaction with an individualised medical intervention which shared key health information and signposted them to important resources (eg, mental health). Future studies across multiple clubs should explore the broader impact of this intervention among deselected male and female Academy footballers. Football clubs should consider integrating a medical after-care process for deselected players as part of routine care.

Psychology research in women's soccer: a scoping review.

Previous research suggests that psychological factors play an important role in trying to explain and predict the participation, performance, and health of player and practitioners in soccer. However, most previous works have focused on specific research questions and included samples from male populations. As part of a larger Fédération Internationale de Football Association (FIFA) project aiming to steer women's soccer research, our purpose with this scoping review was to give an overview of the current state of psychology-related research within women's soccer. We searched five electronic databases up to April 2023, from which 280 original peer-reviewed articles met the inclusion criteria. Included records were inductively coded into 75 specific research topics and nine broader research categories. Population characteristics within each topic and category, and overall publication trends, were identified. The results revealed a growth in research attention, with notable increases in publication rates around the international competitions years, over the last two decades. While a notable number of abstracts did not report sufficient details about population age and/or playing levels, senior elite players were identified as the most common population studied. Most studies examined several topics from different research categories, with research focusing on emotions, moods and/or environmental factors, and the specific the topics of anxiety, stress, and coach behavior, receiving most research attention. Our study provides an informative mapping of all psychology-related research activity within women's soccer, which will enhance researchers' understanding of the current quantity of literature within this complex, heterogeneous, and growing area of research.

The GPCR adaptor protein Norbin regulates S1PR1 trafficking and the morphology, cell cycle and survival of PC12 cells.

Norbin is an adaptor protein that binds numerous G protein-coupled receptors (GPCRs), is highly expressed in neurons, and is essential for a functioning nervous system in rodent models. Yet, beyond its control of neurite outgrowth and synaptic plasticity, few cellular roles of Norbin have been investigated to date. Furthermore, while Norbin is known to regulate the steady-state cell surface levels of several GPCRs, only in one case has the protein been shown to control the agonist-induced receptor internalisation which serves to attenuate GPCR signalling. Here, we generated a Norbin-deficient PC12 cell line which enabled us to study both the cellular functions of Norbin and its roles in GPCR trafficking and signalling. We show that Norbin limits cell size and spreading, and is required for the growth, viability and cell cycle progression of PC12 cells. We also found that Norbin regulates both the steady-state surface level and agonist-induced internalisation of the GPCR sphingosine-1-phosphate receptor 1 (S1PR1) in these cells, suggesting that its role in agonist-dependent GPCR trafficking is more widespread than previously appreciated. Finally, we show that Norbin limits the S1P-stimulated activation of Akt and p38 Mapk, and is required for the activation of Erk in PC12 cells. Together, our findings provide a better understanding of the cellular functions of Norbin and its control of GPCR trafficking.

FIFA football nurse - A task sharing approach in sports and exercise medicine practice in grassroots women's football in low- and middle- income settings. A study protocol for a cluster randomised controlled trial.

Football (soccer) is a very popular team sport among African women and girls, with player numbers continuing to rise at all levels of the sport. Whereas the participation in football and associated injuries are on the rise, there are not enough sports and exercise medicine (SEM) personnel to attend to these women football players. While Africa may not currently have enough SEM trained medical doctors and/or physiotherapists, it has relatively higher numbers of other healthcare workers; for example, nurses, who lead healthcare services provision from community to tertiary levels. The primary objective of this study will be to compare sports medicine practices; injury prevention behaviours; injury risk parameters; incidence and prevalence of injuries and illnesses in teams with and without a Football Nurse during one competitive season in Malawi's Women's football league. This study will be a cluster randomised control trial will recruit 24 teams from the Women's Football League in Malawi, which will be randomised to either the intervention group or the control group. A cohort of 12 nurses will receive training in basic football medicine; after which they will be attached to a total of 12 women's football teams (intervention group) during one competitive season. The Football Nurses will be directly report to a physiotherapist or doctor in their district to whom they will refer serious injuries for investigations, or further management. The teams with Football Nurses will be compared to other teams that will not have Football Nurses. We expect to develop a low cost, sustainable and context relevant solution to manage the treatment gap of football injuries/illnesses in underserved communities such as women's football. Trial registration number: Pan African Clinical Trial Registry (PACTR202205481965514).

Imaging-detected sports injuries and imaging-guided interventions in athletes during the 2022 FIFA football (soccer) World Cup.

OBJECTIVE: To describe imaging-detected musculoskeletal injuries and image-guided interventional procedures during the 2022 FIFA football (soccer) World Cup. MATERIALS AND METHODS: Retrospective analysis of all radiologic examinations performed in a central medical facility for athletes was performed by two board certified musculoskeletal radiologists. Data on muscle, tendon, ligament, cartilage, and bone injuries were collected according to imaging modality and body part. RESULTS: A total of 143 radiology examinations in 94 athletes were evaluated at the central medical facility. Magnetic resonance imaging (MRI) was the most utilized modality (67%), followed by radiography (12%), ultrasonography (9%), and computed tomography (4%). Image-guided interventions corresponded to 8% of all radiological examinations. There were 112 injuries described, affecting muscles and tendons (42%), ligaments (25%), cartilage (21%), and bone (12%). Most injured body parts were thigh (27%), foot and ankle (23%), knee (23%), and hip/groin (8%). Most injured players were within the age range of 24-35 years old (71%). CONCLUSION: Imaging was utilized in 11% of players who participated in the 2022 FIFA World Cup in Qatar. MRI was the most utilized modality, and acute muscle tears were the most diagnosed type of injury. Diagnostic imaging played an important role in diagnosing sports-related injuries during the 2022 FIFA World Cup.

Leadership experiences of elite football team physicians during the COVID-19 pandemic: a pilot study.

OBJECTIVES: The purpose of this study was to explore the leadership experiences of elite football team physicians during the COVID-19 pandemic. METHODS: A pilot-study based on a cross-sectional design by means of an electronic survey was conducted. The survey relied on 25 questions divided into distinct sections including among others professional and academic experience, leadership experiences and perspectives. RESULTS: A total of 57 physicians (91% male; mean age: 43 years) gave their electronic informed consent and completed the survey. All participants agreed that the demands of their role had increased during the COVID-19 pandemic. Fifty-two (92%) participants reported that they felt they were expected to take more of a leadership role during the COVID-19 pandemic. Eighteen (35%) reported feeling under pressure to make clinical decisions which were not in keeping with best clinical practice. Additional roles, duties and demands expected of team doctors during the COVID-19 pandemic were subdivided into communication, decision-making, logistical, and public health demands. CONCLUSION: The findings from this pilot study suggest that the way in which team physicians at professional football clubs operate has altered since the onset of the COVID-19 pandemic, with greater demands placed on leadership skills including decision-making, communication and ethical stewardship. This has potential implications for sporting organisations, clinical practice and research.

Football-specific extension of the IOC consensus statement: methods for recording and reporting of epidemiological data on injury and illness in sport 2020.

Several sports have published consensus statements on methods and reporting of epidemiological studies concerning injuries and illnesses with football (soccer) producing one of the first guidelines. This football-specific consensus statement was published in 2006 and required an update to align with scientific developments in the field. The International Olympic Committee (IOC) recently released a sports-generic consensus statement outlining methods for recording and reporting epidemiological data on injury and illness in sport and encouraged the development of sport-specific extensions.The Fédération Internationale de Football Association Medical Scientific Advisory Board established a panel of 16 football medicine and/or science experts, two players and one coach. With a foundation in the IOC consensus statement, the panel performed literature reviews on each included subtopic and performed two rounds of voting prior to and during a 2-day consensus meeting. The panel agreed on 40 of 75 pre-meeting and 21 of 44 meeting voting statements, respectively. The methodology and definitions presented in this comprehensive football-specific extension should ensure more consistent study designs, data collection procedures and use of nomenclature in future epidemiological studies of football injuries and illnesses regardless of setting. It should facilitate comparisons across studies and pooling of data.

FIFA Arab Cup tournament with full capacity of spectators during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: We sought to assess the risk of COVID-19 and seasonal flu including respiratory syncytial (RSV) and influenza viruses during the FIFA Arab Cup 2021 in Qatar with full capacity of spectators. We also, evaluated the post-event attitude toward resumption of mass football events. METHODS: This was a cross-sectional study in which spectators (age ≥ 18 years) were invited for reverse-transcription PCR testing for COVID-19 and seasonal flu. At the same time, between 7 and 14 days after the event, the participants completed a self-administered questionnaire regarding their concerns during the tournament. RESULTS: The tournament included 16 international football teams from the Arab countries. As per the study protocol, 10,000 spectators were approached and 6,475 participated. Among the participants, 4,195 (65.1%), 2,253 (34.9%) and 27 (0.4%) were vaccinated with 2 doses, vaccinated with 3 doses, and recovered from SARS-Cov-2 infection, respectively. There were 61 (0.9%), 41(0.6%) and 11(0.2%) participants who tested positive for COVID-19, RSV and influenza (A/B), respectively. The average cycle threshold (Ct) value for COVID-19 positive cases was 26.1±7.3. Among those who were electronically approached, 6,102 completed the survey whereas 373 had incomplete survey. Overall, 2069 (33.9%) participants reported symptoms that theoretically could be related to COVID-19, of them 39 had positive PCR test (1.9%). Spectators (94.3%) were optimistic about returning sport events to the pre-pandemic status. CONCLUSIONS: There was no significant increase in the daily COVID-19 cases during FIFA Arab Cup 2021 with a full capacity of spectators. Therefore, upcoming mass football events can be held safely.

Video review of the frequency and assessment of head impacts during the FIFA Arab Cup 2021TM.

We used injury spotters and video footage review to establish the frequency of head impacts, their characteristics, and the subsequent medical assessment during the FIFA Arab Cup 2021TM. Six defined video signs of potential concussion based on an international consensus were used. A total of 88 head impacts were observed, with a median of 2 (IQR 1.5-4, range 0-7) head impacts per match, of which 44 (50%) resulted in on-pitch medical assessment. The median assessment duration was 51s (IQR 34-65s, range 19-262s). The most common mechanism was head-to-head contact (27% of all impacts and 43% of impacts with medical assessment). Seven head impacts showed video signs of potential concussion: six had one sign and one had two signs. The concussion substitution was used in three incidents. Head impacts during the FIFA Arab Cup were common and a median of 1 head impact per game required an on-pitch medical assessment. Only 8% of the head impacts showed any video sign of potential concussion, and only 3% resulted in a concussion substitution. The medical on-pitch assessments appeared too short (<1 min) to allow an appropriate assessment of all head impacts, indicating a need for further evaluation. Further standardisation of the injury spotter's role in football is recommended.

IOC consensus statement on recommendations and regulations for sport events in the heat.

This document presents the recommendations developed by the IOC Medical and Scientific Commission and several international federations (IF) on the protection of athletes competing in the heat. It is based on a working group, meetings, field experience and a Delphi process. The first section presents recommendations for event organisers to monitor environmental conditions before and during an event; to provide sufficient ice, shading and cooling; and to work with the IF to remove regulatory and logistical limitations. The second section summarises recommendations that are directly associated with athletes' behaviours, which include the role and methods for heat acclimation; the management of hydration; and adaptation to the warm-up and clothing. The third section explains the specific medical management of exertional heat stroke (EHS) from the field of play triage to the prehospital management in a dedicated heat deck, complementing the usual medical services. The fourth section provides an example for developing an environmental heat risk analysis for sport competitions across all IFs. In summary, while EHS is one of the leading life-threatening conditions for athletes, it is preventable and treatable with the proper risk mitigation and medical response. The protection of athletes competing in the heat involves the close cooperation of the local organising committee, the national and international federations, the athletes and their entourages and the medical team.

Research on women's football: a scoping review.

AIM: This study aims to scope available peer-reviewed literature published in a FIFA language to understand the current quantity of research on women's football. METHODS: Five databases were searched on the 15/12/2019. Studies were included when containing original research published in a peer-reviewed journal around female competitive football of any level, any age and on any subject. Author, journal, title and abstract of all included studies were scoped. Population assessed number of participants, level of play, age level of football and publication theme(s) were extracted. RESULTS: A total of 1,634 articles were scoped. The oldest publication dated back to 1939, whilst a total of 202 studies were gathered from 2019. The publication theme most frequently researched was sports medicine (N = 521) followed by strength and conditioning (N = 331) and sociology (N = 299). The majority of studies has focussed on elite (N = 442), senior (N = 977) players. CONCLUSION: A continuous growth in research attention has been seen. However, the numbers are not comparable to current research output levels in men's football. This study represents an essential first step in a larger 'research agenda-setting' project to determine research priorities for women's football during the next 10 years.

Correlation between preseason body composition and sports injury in an English Premier League professional football team.

Objectives: To identify the correlation between preseason body composition and incidence coupled with injury burden throughout the season in adult male professional football players. Methods: A retrospective case series was performed for linear regression analysis of preseason body composition variables and injury data. R2 >0.10 was deemed of adequate correlation. Results: All 36 professional football players in the male first team of an English Premier League professional football team were recruited, with none lost to follow-up. The total and mean incidence of injuries was 83.00 and 2.31 (95% CI 1.72 to 2.89), respectively. The mean injury burden was 58.32 (95% CI 37.67 to 78.98) days missed. Simple linear regression analysis indicated no significant or adequate correlations between incidence and preseason body composition variables. Injury burden revealed non-significant adequate negative correlations to body mass (R2=0.17), body mass index (BMI) (R2=0.15), waist circumference (R2=0.17), total bone mineral density (BMD) (R2=0.11) and mean embedded structures (R2=0.10). Conclusions: Players with decreased body mass, BMI, waist circumference, total BMD and mean embedded structures may be prone to greater injury burden. Further studies with a larger sample size that incorporates multiple football teams are warranted to investigate this.

Chk1 inhibitor-induced DNA damage increases BFL1 and decreases BIM but does not protect human cancer cell lines from Chk1 inhibitor-induced apoptosis.

V158411 is a potent, selective Chk1 inhibitor currently in pre-clinical development. We utilised RNA-sequencing to evaluate the gene responses to V158411 treatment. BCL2A1 was highly upregulated in U2OS cells in response to V158411 treatment with BCL2A1 mRNA increased > 400-fold in U2OS but not HT29 cells. Inhibitors of Chk1, Wee1 and topoisomerases but not other DNA damaging agents or inhibitors of ATR, ATM or DNA-PKcs increased BFL1 and decreased BIM protein. Increased BFL1 appeared limited to a subset of approximately 35% of U2OS cells. Out of 24 cell lines studied, U2OS cells were unique in being the only cell line with low basal BFL1 levels to be increased in response to DNA damage. Induction of BFL1 in U2OS cells appeared dependent on PI3K/AKT/mTOR/MEK pathway signalling but independent of NF-κB transcription factors. Inhibitors of MEK, mTOR and PI3K effectively blocked the increase in BFL1 following V15841 treatment. Increased BFL1 expression did not block apoptosis in U2OS cells in response to V158411 treatment and cells with high basal expression of BFL1 readily underwent caspase-dependent apoptosis following Chk1 inhibitor therapy. BFL1 induction in response to Chk1 inhibition appeared to be a rare event that was dependent on MEK/PI3K/AKT/mTOR signalling.

Health conditions among retired professional footballers: a scoping review.

Objective: To conduct a scoping review providing an overview of the health conditions occuring in retired male and female professional footballers, with an emphasis on musculoskeletal, mental, neurocognitive, cardiovascular and reproductive health conditions. Methods: In January 2022, a comprehensive systematic literature search in three databases (MEDLINE via PubMed, SPORTDiscus via EBSCOhost and EMBASE) was conducted for common health conditions among retired male and female professional footballers. Primary research studies (full text available online) which described the incidence or prevalence of a health condition (musculoskeletal, mental, neurocognitive, cardiovascular, reproductive) among retired male and female professional footballers were included for review. Case reports, qualitative research and grey literature were omitted. Results: In total, 917 eligible articles were identified from the databases, with 41 meeting the eligibility criteria. Osteoarthritis of the hip, knee and ankle were found to be common among retired professional footballers. Mental health symptoms (eg, anxiety, depression) are experienced by retired male and female professional footballers. The incidence of neurocognitive disease appears to be higher among retired male professional footballers than among matched controls. There is very limited evidence examining the presence of health conditions in retired female professional footballers. Conclusion: Osteoarthritis of the lower limb, musculoskeletal pain and mental health symptoms are common among retired professional footballers. Knowledge about the occurrence and timing of musculoskeletal, mental health and neurocognitive conditions among retired professional footballers can be used by a wide range of stakeholders to proactively intervene during and after a player's career to mitigate risk.

The exchange of health and performance information when transitioning from club to National football teams: A Delphi survey of National team practitioners.

OBJECTIVES: To establish agreement in National team contexts when players transition from club to National team about (i) what medical and physical information to collect, (ii) how to use information (iii) identifying challenges to collection and (iv) collection methods. DESIGN: Delphi survey. METHODS: A series of sequential online questionnaires were sent to heads of medical and performance of the 32 National teams following the FIFA 2018 World Cup. Two separate Delphi's; 'Medical' and 'Physical' were administered. The 'Medical' respondent was the person responsible for player health. 'Physical' referred to the person responsible for physical performance. Content analyses were performed, with subsequent rounds designed according to responses of the previous. Agreement was considered at ≥70%. RESULTS: Twenty-three Medical (72%) and 14 (44%) Physical heads participated in Round 1 (3 rounds total). Seventeen Medical and 12 Physical respondents completed all rounds. Medical information agreed upon injury epidemiology, screening and injury treatment strategies. Physical information included training/match-loads, fatigue, wellness and current exercise programmes. Both Medical and Physical agreed information should be used to plan and individualise player programmes. Additionally medical information should guide coaches' national team selection. Communication, willingness to share and quality/completeness of information were agreed as main challenges. Medical and Physical respondents agreed a standardised reporting form and electronic shared database as best option to collect information. CONCLUSIONS: Our findings highlight the importance of health and performance information exchange between national and club teams. Further, this exchange should be cooperative, symbiotic and a two-way process to assist with improving player health.