Illness is more prevalent than injury in trail runners participating in a mountainous ultra trail race.

OBJECTIVES: Trail running is a popular off-road sport involving running in natural environments over various terrains, often in remote locations. This study aims to investigate the epidemiology and risk factors of injuries and illnesses, i.e. medical encounters, on race day among trail runners in a high-altitude ultra trail race. METHODS: This descriptive cross-sectional study on an ultra trail race (38 km, 65 km and 100 km) in South Africa, included participants 18 years or older. Of the 331 race participants, 285(86.1%) consented to participate in the study. Data collection included demographic details, injuries (body region, specific body area, tissue type, pathology) and illnesses (organ system, symptom cluster, etiology). Risk factor analysis includes sex, age, weight, height, race distance, illness and injury history, training and running experience. Frequency (n, %), prevalence (%) and odds ratios (OR; 95%CI) are reported. RESULTS: Eighty-nine (31.2%) individuals reported 131 medical encounters [49 injuries (37.4%); 82 illnesses (62.6%)]. Injuries were sustained by 14.7% of athletes, and 22.5% reported illnesses. For injuries, the lower limb was mainly involved (n = 41; 83.7%). Most injuries affected the foot (n = 18; 36.7%), ankle (n = 10; 20.4%) and knee (n = 7; 14.3%). Tissue types mainly involved skin (n = 21; 42.8%), ligament (n = 7; 14.3%) and muscle (n = 7; 14.3%). Multiple (n = 45; 54.9%) and gastrointestinal (n = 17; 20.7%) organ systems were mainly involved in illnesses. Only 100 km runners reported dehydration (n = 28; 31.5%), and one in every six of these runners (n = 5; 17.9%) did not finish. Runners reporting fatigue (n = 21; 23.6%) had a high (n = 8; 38.1%) did not finish rate. Two in every five participants (n = 36; 40.4%) with a medical encounter, did not finish. No medical encounter-associated risk factors were identified. CONCLUSIONS: Illnesses were more common than injuries during the mountainous ultra trail race. Sustaining a medical encounter increased the chance of not completing the race. Further research on the epidemiology of race day medical encounters in trail running is required.

The Physical Demands of Wheelchair Tennis Match Play: A Systematic Review with Meta-analysis.

BACKGROUND: Wheelchair tennis, a globally popular sport, features a professional tour spanning 40 countries and over 160 tournaments. Despite its widespread appeal, information about the physical demands of wheelchair tennis is scattered across various studies, necessitating a comprehensive systematic review to synthesise available data. OBJECTIVE: The aim was to provide a detailed synthesis of the physical demands associated with wheelchair tennis, encompassing diverse factors such as court surfaces, performance levels, sport classes, and sexes. METHODS: We conducted comprehensive searches in the PubMed, Embase, CINAHL, and SPORTDiscus databases, covering articles from inception to March 1, 2023. Forward and backward citation tracking from the included articles was carried out using Scopus, and we established eligibility criteria following the Population, Exposure, Comparison, Outcome, and Study design (PECOS) framework. Our study focused on wheelchair tennis players participating at regional, national, or international levels, including both juniors and adults, and open and quad players. We analysed singles and doubles matches and considered sex (male, female), sport class (open, quad), and court surface type (hard, clay, grass) as key comparative points. The outcomes of interest encompassed play duration, on-court movement, stroke performance, and physiological match variables. The selected study designs included observational cross-sectional, longitudinal, and intervention studies (baseline data only). We calculated pooled means or mean differences with 95% confidence intervals (CIs) and employed a random-effects meta-analysis with robust variance estimation. We assessed heterogeneity using Cochrane Q and 95% prediction intervals. RESULTS: Our literature search retrieved 643 records, with 24 articles meeting our inclusion criteria. Most available information focused on international male wheelchair tennis players in the open division, primarily competing in singles on hard courts. Key findings (mean [95% CI]) for these players on hard courts were match duration 65.9 min [55.0-78.8], set duration 35.0 min [28.2-43.5], game duration 4.6 min [0.92-23.3], rally duration 6.1 s [3.7-10.2], effective playing time 19.8% [18.9-20.7], and work-to-rest ratio 1:4.1 [1:3.7-1:4.4]. Insufficient data were available to analyse play duration for female players. However, for the available data on hard court matches, the average set duration was 34.8 min [32.5-37.2]. International male players on hard court covered an average distance per match of 3859 m [1917-7768], with mean and peak average forward speeds of 1.06 m/s [0.85-1.32] and 3.55 m/s [2.92-4.31], respectively. These players executed an average of 365.9 [317.2-422.1] strokes per match, 200.6 [134.7-299.0] per set, 25.4 [16.7-38.7] per game, and 3.4 [2.6-4.6] per rally. Insufficient data were available for a meta-analysis of female players' on-court movement and stroke performance. The average and peak heart rates of international male players on hard court were 134.3 [124.2-145.1] and 166.0 [132.7-207.6] beats per minute, and the average match heart rate expressed as a percentage of peak heart rate was 74.7% [46.4-100]. We found no studies concerning regional players or juniors, and only one study on doubles match play. CONCLUSIONS: While we present a comprehensive overview of the physical demands of wheelchair tennis, our understanding predominantly centres around international male players competing on hard courts in the open division. To attain a more comprehensive insight into the sport's physical requirements, future research should prioritise the inclusion of data on female and quad players, juniors, doubles, and matches played on clay and grass court surfaces. Such endeavours will facilitate the development of more tailored and effective training programmes for wheelchair tennis players and coaches. The protocol for this systematic review was registered a priori at the International Platform of Registered Systematic Review and Meta-analysis Protocols (Registration https://doi.org/10.37766/inplasy2023.3.0060 ).

The post-septic peripheral myeloid compartment reveals unexpected diversity in myeloid-derived suppressor cells.

Introduction: Sepsis engenders distinct host immunologic changes that include the expansion of myeloid-derived suppressor cells (MDSCs). These cells play a physiologic role in tempering acute inflammatory responses but can persist in patients who develop chronic critical illness. Methods: Cellular Indexing of Transcriptomes and Epitopes by Sequencing and transcriptomic analysis are used to describe MDSC subpopulations based on differential gene expression, RNA velocities, and biologic process clustering. Results: We identify a unique lineage and differentiation pathway for MDSCs after sepsis and describe a novel MDSC subpopulation. Additionally, we report that the heterogeneous response of the myeloid compartment of blood to sepsis is dependent on clinical outcome. Discussion: The origins and lineage of these MDSC subpopulations were previously assumed to be discrete and unidirectional; however, these cells exhibit a dynamic phenotype with considerable plasticity.

Return to Sports Following Sports-Related Concussion in Collision Sports: An Expert Consensus Statement Using the Modified Delphi Technique.

PURPOSE: To perform a Delphi consensus for return to sports (RTS) following sports-related concussion (SRC). METHODS: Open-ended questions in rounds 1 and 2 were answered. The results of the first 2 rounds were used to develop a Likert-style questionnaire for round 3. If agreement at round 3 was ≤80% for an item, if panel members were outside consensus or there were >30% neither agree/disagree responses, the results were carried forward into round 4. The level of agreement and consensus was defined as 90%. RESULTS: Individualized graduated RTS protocols should be used. A normal clinical, ocular and balance examination with no more headaches, and asymptomatic exertional test allows RTS. Earlier RTS can be considered if athletes are symptom free. The Sports Concussion Assessment Tool 5 and vestibular and ocular motor screening are recognized as useful tools to assist in decision-making. Ultimately RTS is a clinical decision. Baseline assessments should be performed at both collegiate and professional level and a combination of neurocognitive and clinical tests should be used. A specific number of recurrent concussions for season-or career-ending decisions could not be determined but will affect decision making for RTS. CONCLUSIONS: Consensus was achieved for 10 of the 25 RTS criteria: early RTS can be considered earlier than 48 to 72 hours if athletes are completely symptom-free with no headaches, a normal clinical, ocular and balance examination. A graduated RTS should be used but should be individualized. Only 2 of the 9 assessment tools were considered to be useful: Sports Concussion Assessment Tool 5 and vestibular and ocular motor screening. RTS is mainly a clinical decision. Only 31% of the baseline assessment items achieved consensus: baseline assessments should be performed at collegiate and professional levels using a combination of neurocognitive and clinical tests. The panel disagreed on the number of recurrent concussions that should be season- or career-ending. LEVEL OF EVIDENCE: Level V, expert Opinion.

Training for shorter ultra-trail races results in a higher injury rate, a more diverse injury profile, and more severe injuries: 2022 Mac ultra races.

OBJECTIVES: Determine and compare the epidemiology, clinical characteristics, and injury severity among race entrants training towards different ultra-trail race distances. DESIGN: Retrospective cross-sectional study. SETTING: The six months training period before the 2022 Mac Ultra races (46 km, 80 km, 161 km and 322 km). PARTICIPANTS: Of the 245 race entrants, 162 (66% of Mac ultra-trail runners) consented to analyse their data. OUTCOME MEASURES: Injury rate (injuries per 1000 h of running), point prevalence (% of currently injured participants), injury severity (time loss), and the frequency (n, %) of injuries reported during pre-race medical screening in the six months before the race. Using inferential statistics, we compared the injury rates between the different race distance categories (46 km, 80 km, 161 km, 322 km). All tests were performed at a 5% level of significance. RESULTS: We reported a statistically significantly higher injury rate among 46 km study participants (3.09 injuries per 1000 h) compared to the injury rates reported among 80 km (0.68 injuries per 1000 h; p = 0.001) and 161 km (1.09 injuries per 1000 h; p = 0.028) participants. The lower limb (89%) was the most injured anatomical region, with only 46 km study participants reporting upper limb, trunk, and head injuries (11%). Muscle/tendon was the most reported injured tissue type (56%), with muscle injuries (31%) the most reported pathology type. Shorter distance ultra-trail runners reported the highest injury severity. CONCLUSION: Ultra-trail runners training towards shorter ultra-trail distance races presented with a higher injury rate, more diverse injury profile, and a higher injury severity.

On-Field and Pitch-Side (Sideline) Assessment of Sports Concussion in Collision Sports: An Expert Consensus Statement Using the Modified Delphi Technique.

PURPOSE: To perform a Delphi consensus for on-field and pitch-side assessment of sports-related concussion (SRC). METHODS: Open-ended questions in rounds 1 and 2 were answered. The results of the first 2 rounds were used to develop a Likert-style questionnaire for round 3. If agreement at round 3 was ≤80% for an item, if panel members were outside consensus, or there were >30% neither agree/disagree responses, the results were carried forward into round 4. The level of agreement and consensus was defined as 90%. RESULTS: Loss of consciousness (LOC) or suspected LOC, motor incoordination/ataxia, balance disturbance, confusion/disorientation, memory disturbance/amnesia, blurred vision/light sensitivity, irritability, slurred speech, slow reaction time, lying motionless, dizziness, headaches/pressure in the head, falling to the ground with no protective action, slow to get up after a hit, dazed look, and posturing/seizures were clinical signs of SRC and indicate removal from play. Video assessment is helpful but should not replace clinical judgment. LOC/unresponsiveness, signs of cervical spine injury, suspicion of other fractures (skull/maxillo-facial), seizures, Glasgow Coma Scale score <14 and abnormal neurologic examination findings are indications for hospitalization. Return to play should only be considered when no clinical signs of SRC are present. Every suspected concussion should be referred to an experienced physician. CONCLUSIONS: Consensus was achieved for 85% of the clinical signs indicating concussion. On-field and pitch-side assessment should include the observation of the mechanism, a clinical examination, and cervical spine assessment. Of the 19 signs and red flags requiring removal from play, consensus was reached for 74%. Normal clinical examination and HIA with no signs of concussion allow return to play. Video assessment should be mandatory for professional games but should not replace clinical decision-making. Sports Concussion Assessment Tool, Glasgow Coma Scale, vestibular/ocular motor screening, Head Injury Assessment Criteria 1, and Maddocks questions are useful tools. Guidelines are helpful for non-health professionals. LEVEL OF EVIDENCE: Level V, expert opinion.

Task-Shifting: Can Community Health Workers Be Part of the Solution to an Inactive Nation?

Background: In low-to-middle income countries (LMICs), there is a growing burden of non-communicable diseases (NCDs) placing strain on the facilities and human resources of healthcare systems. Prevention strategies that include lifestyle behavior counseling have become increasingly important. We propose a potential solution to the growing burden of NCDs through an expansion of the role for community health workers (CHWs) in prescribing and promoting physical activity in public health settings. This discussion paper provides a theoretical model for task-shifting of assessment, screening, counseling, and prescription of physical activity to CHWs. Five proposed tasks are presented within a larger model of service delivery and provide a platform for a structured, standardized, physical activity prevention strategy aimed at NCDs using CHWs as an integral part of reducing the burden of NCDs in LMICs. However, for effective implementation as part of national NCD plans, it is essential that CHWs received standardized, ongoing training and supervision on physical activity and other lifestyle behaviors to optimally impact community health in low resource settings.

Variable Bessel Beam Profiles Generated through Refraction by Liquid Media.

Various methods have been employed to produce Bessel beams (BBs), with axicon-based techniques remaining the most efficient. Among the limitations of axicons are manufacturing defects such as oblate tips and difficulty in tuning the generated BBs. In this work, we combine the effect of a blunt-tip axicon with refraction using various combinations of liquid media to generate variable BB intensity profiles. The output BBs from the axicon are made to pass through a custom-built fluid chamber and magnified using a telescope system. When traversing an empty chamber, the Bessel beam core diameter is measured to be 773.8 µm at propagation distance z' = 30 cm. The core diameter increases as the beam passes through a chamber containing different liquids as a result of an effective axicon-telescope distance produced by the indices of refraction of the pertinent fluids. Bessel beams modified by the fluid chamber maintain the properties of non-diffraction and self-healing.

Determination of the Prevalence of Knee and Hip Clinical Osteoarthritis in the Active Professional Male Footballer and Its Association with Pain, Function, Injury and Surgery.

OBJECTIVE: To comment on and explore (1) the prevalence of clinical knee and hip osteoarthritis (OA); (2) the association between pain or function and clinical knee or hip OA; (3) the association between injury or surgery and clinical knee or hip OA. METHODS: Participants were recruited from FIFPRO members. A total of 101 footballers consented to answer (1) a developed questionnaire, (2) patient-reported outcome measures, and (3) be evaluated by their team physician for clinical knee or hip OA. RESULTS: Of the 53% evaluated for clinical knee and hip OA, a prevalence of 9.43% and 7.55% of knee and hip OA, respectively, was found. There was a significant and strong association between knee (p = 0.033; Cramers v Value = 0.523) and hip pain (p = 0.005; Cramers v Value = 0.602) and clinical OA. A significant association existed between Hip dysfunction and Osteoarthritis Outcome short form Scores and clinical OA of the hip (p = 0.036). The odds of clinical knee OA were 1.5 and 4.5 times more after one or more injuries or surgeries, respectively. There was no association between playing position and clinical OA. CONCLUSION: There is a low prevalence of a clinical knee or hip OA in the active professional male footballer. Pain may be a valid symptom to predict or monitor knee or hip OA. Validated assessment tools should be utilised to identify a negative effect on function. The odds of developing clinical OA in the knee with the number of injuries or surgeries. The hip presents with earlier clinical signs of OA compared to the knee.

The illness burden of gastrointestinal illness is two times higher if it is associated with systemic symptoms and signs: a cross-sectional study of the super rugby tournament over 5 seasons (102,738 player-days).

BACKGROUND: Gastrointestinal tract illness (GITill) in rugby players is underreported. The incidence, severity (% time loss illness, days lost per illness) and burden of GITill with/without systemic symptoms and signs in professional South African male rugby players during the Super Rugby tournament (2013-2017) are reported. METHODS: Team physicians completed daily illness logs of players (N.=537; 1141 player-seasons, 102738 player-days). The incidence (illnesses/1000 player-days, 95% CI), severity (% ≥1-day time-loss; days until return-to-play [DRTP]/single illness [mean: 95% CI]) and illness burden (IB: days lost to illness/1000 player-days) for the subcategories of GITill with/without systemic symptoms and signs (GITill+ss; GITill-ss), and gastroenteritis with/without systemic symptoms and signs (GE+ss; GE-ss) are reported. RESULTS: The incidence of all GITill was 1.0 (0.8-1.2). Incidence was similar for GITill+ss 0.6 (0.4-0.8) and GITill-ss 0.4 (0.3-0.5; P=0.0603). Incidence of GE+ss 0.6 (0.4-0.7) was higher than GE-ss 0.3 (0.2-0.4; P=0.0045). GITill caused ≥1-day time-loss in 62% of cases (GE+ss 66.7%; GE-ss 53.6%). GITill caused an average of 1.1 DRTP/single GITill, which was similar for subcategories. IB of GITill+ss was higher than GITill-ss (IB Ratio: 2.1 [1.1-3.9; P=0.0253]). IB for GITill+ss is 2 times higher than GITill-ss (IB Ratio: 2.1 [1.1-3.9]; P=0.0253); and GE+ss >3 times higher than GE-ss (IB Ratio: 3.0 [1.6-5.8]; P=0.0007). CONCLUSIONS: GITill accounted for 21.9% of all illnesses during the Super Rugby tournament, with >60% of GITill resulting in time-loss. The average DRTP/single illness was 1.1. GITill+ss and GE+ss resulted in higher IB. Targeted interventions to reduce the incidence and severity of GITill+ss and GE+ss should be developed.

Physical Demands of Tennis Across the Different Court Surfaces, Performance Levels and Sexes: A Systematic Review with Meta-analysis.

BACKGROUND: Tennis is a multidirectional high-intensity intermittent sport for male and female individuals played across multiple surfaces. Although several studies have attempted to characterise the physical demands of tennis, a meta-analysis is still lacking. OBJECTIVE: We aimed to describe and synthesise the physical demands of tennis across the different court surfaces, performance levels and sexes. METHODS: PubMed, Embase, CINAHL and SPORTDiscus were searched from inception to 19 April, 2022. A backward citation search was conducted for included articles using Scopus. The PECOS framework was used to formulate eligibility criteria. POPULATION: tennis players of regional, national or international playing levels (juniors and adults). EXPOSURE: singles match play. Comparison: sex (male/female), court surface (hard, clay, grass). OUTCOME: duration of play, on-court movement and stroke performance. STUDY DESIGN: cross-sectional, longitudinal. Pooled means or mean differences with 95% confidence intervals were calculated. A random-effects meta-analysis with robust variance estimation was performed. The measures of heterogeneity were Cochrane Q and 95% prediction intervals. Subgroup analysis was used for different court surfaces. RESULTS: The literature search generated 7736 references; 64 articles were included for qualitative and 42 for quantitative review. Mean [95% confidence interval] rally duration, strokes per rally and effective playing time on all surfaces were 5.5 s [4.9, 6.3], 4.1 [3.4, 5.0] and 18.6% [15.8, 21.7] for international male players and 6.4 s [5.4, 7.6], 3.9 [2.4, 6.2] and 20% [17.3, 23.3] for international female players. Mean running distances per point, set and match were 9.6 m [7.6, 12.2], 607 m [443, 832] and 2292 m [1767, 2973] (best-of-5) for international male players and 8.2 m [4.4, 15.2], 574 m [373, 883] and 1249 m [767, 2035] for international female players. Mean first- and second-serve speeds were 182 km·h-1 [178, 187] and 149 km·h-1 [135, 164] for international male players and 156 km·h-1 95% confidence interval [151, 161] and 134 km·h-1 [107, 168] for international female players. CONCLUSIONS: The findings from this study provide a comprehensive summary of the physical demands of tennis. These results may guide tennis-specific training programmes. We recommend more consistent measuring and reporting of data to enable future meta-analysts to pool meaningful data. CLINICAL TRIAL REGISTRATION: The protocol for this systematic review was registered a priori at the Open Science Framework (Registration DOI https://doi.org/10.17605/OSF.IO/MDWFY ).

Seroprevalence of IgG Rubella among Infants with Features Suggestive of Congenital Rubella Syndrome at a Tertiary Hospital in North Western Tanzania.

Background: Congenital Rubella Syndrome (CRS) is among the causes of infant mortality and lifelong disability due to severe birth defects. There has been an increasing number of neonates born with congenital abnormalities suggesting CRS, at the same time the rubella seroprevalence among pregnant mothers and healthy school children in the northwestern Tanzania has been noted to be alarmingly high. This study aimed to determine prevalence of rubella antibodies and associated factors among infants suspected to have CRS. Methods: This cross-sectional study included 174 infants aged ≤ 12 months with at least one clinical features of CRS. The study was conducted between Septembers 2017 and March 2018 at Bugando Medical Centre, a consultant teaching hospital in North Western Tanzania. Collection of Social demographic and other relevant information was done hand in hand with screening for clinical symptoms suggestive of CRS and Blood samples were collected. Indirect enzyme-linked immunosorbent assay (ELISA) Test were conducted on collected sera to test for specific Rubella IgM and IgG antibodies. Results: The majority of enrolled infants were below 1 year of age; of these 83 (47.7%) were neonates and only 13.2% had received MR vaccine. Out of these, 111 (63.8%, 95%CI: 56.6-70.9) were IgG Rubella seropositive whereas none was IgM Rubella seropositive. In multivariate logistic regression analysis being neonate was the only factor that independently predicted rubella IgG seropositivity (OR 2.3; 95% CI 1.2 - 4.4; p=0.012). Conclusion: A significant proportion children (<12 months) with suspected CRS are IgG seropositive which is predicted by being a neonate (0-4weeks); this indicates high maternal seroprevalence and hence extended surveillance and measures to target women of child bearing age are recommended.

Development of a trail running injury screening instrument: A multiple methods approach.

OBJECTIVE: To develop a trail running injury screening instrument (TRISI) for utilisation as clinical decision aid in determining if a trail runner is at an increased risk for injury. DESIGN: Multiple methods approach. METHODS: The study utilised five phases 1) identification of injury risk factors 2) determining the relevance of each identified risk factor in a trail running context, 3) creating the content of the Likert scale points from 0 to 4, 4) rescaling the Likert scale points to determine numerical values for the content of each Likert scale point, and 5) determining a weighted score for each injury risk factor that contributes to the overall combined composite score. RESULTS: Of the 77 identified injury risk factors, 26 were deemed relevant in trail running. The weighted score for each injury risk factor ranged from 2.21 to 5.53 with the highest calculated score being 5.53. The final TRISI includes risk categories of training, running equipment, demographics, previous injury, behavioural, psychological, nutrition, chronic disease, physiological, and biomechanical factors. CONCLUSION: The developed TRISI aims to assist the clinician during pre-race injury screening or during a training season to identify meaningful areas to target in designing injury risk management strategies and/or continuous health education.

COVID-19 Lockdown: A Global Study Investigating the Effect of Athletes' Sport Classification and Sex on Training Practices.

PURPOSE: To investigate differences in athletes' knowledge, beliefs, and training practices during COVID-19 lockdowns with reference to sport classification and sex. This work extends an initial descriptive evaluation focusing on athlete classification. METHODS: Athletes (12,526; 66% male; 142 countries) completed an online survey (May-July 2020) assessing knowledge, beliefs, and practices toward training. Sports were classified as team sports (45%), endurance (20%), power/technical (10%), combat (9%), aquatic (6%), recreational (4%), racquet (3%), precision (2%), parasports (1%), and others (1%). Further analysis by sex was performed. RESULTS: During lockdown, athletes practiced body-weight-based exercises routinely (67% females and 64% males), ranging from 50% (precision) to 78% (parasports). More sport-specific technical skills were performed in combat, parasports, and precision (∼50%) than other sports (∼35%). Most athletes (range: 50% [parasports] to 75% [endurance]) performed cardiorespiratory training (trivial sex differences). Compared to prelockdown, perceived training intensity was reduced by 29% to 41%, depending on sport (largest decline: ∼38% in team sports, unaffected by sex). Some athletes (range: 7%-49%) maintained their training intensity for strength, endurance, speed, plyometric, change-of-direction, and technical training. Athletes who previously trained ≥5 sessions per week reduced their volume (range: 18%-28%) during lockdown. The proportion of athletes (81%) training ≥60 min/session reduced by 31% to 43% during lockdown. Males and females had comparable moderate levels of training knowledge (56% vs 58%) and beliefs/attitudes (54% vs 56%). CONCLUSIONS: Changes in athletes' training practices were sport-specific, with few or no sex differences. Team-based sports were generally more susceptible to changes than individual sports. Policy makers should provide athletes with specific training arrangements and educational resources to facilitate remote and/or home-based training during lockdown-type events.

Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation.

Chronic inflammation is a major driver of chronic inflammatory diseases (CIDs), with a tremendous impact worldwide. Besides its function as a pathological calcification inhibitor, vitamin K-dependent protein Gla-rich protein (GRP) was shown to act as an anti-inflammatory agent independently of its gamma-carboxylation status. Although GRP's therapeutic potential has been highlighted, its low solubility at physiological pH still constitutes a major challenge for its biomedical application. In this work, we produced fluorescein-labeled chitosan-tripolyphosphate nanoparticles containing non-carboxylated GRP (ucGRP) (FCNG) via ionotropic gelation, increasing its bioavailability, stability, and anti-inflammatory potential. The results indicate the nanosized nature of FCNG with PDI and a zeta potential suitable for biomedical applications. FCNG's anti-inflammatory activity was studied in macrophage-differentiated THP1 cells, and in primary vascular smooth muscle cells and chondrocytes, inflamed with LPS, TNFα and IL-1ß, respectively. In all these in vitro human cell systems, FCNG treatments resulted in increased intra and extracellular GRP levels, and decreased pro-inflammatory responses of target cells, by decreasing pro-inflammatory cytokines and inflammation mediators. These results suggest the retained anti-inflammatory bioactivity of ucGRP in FCNG, strengthening the potential use of ucGRP as an anti-inflammatory agent with a wide spectrum of application, and opening up perspectives for its therapeutic application in CIDs.

Longer distance races and slower running pace are associated with Exercise associated collapse: SAFER XXV study in 153,208 distance runners.

BACKGROUND: Exercise associated collapse (EAC) is a common medical encounter at distance running events. Risk factors associated with EAC are not well documented. The objective is to determine the overall incidence of EAC and identify risk factors associated with EAC in 21.1-km and 56-km runners. METHODS: A cross-sectional analysis of 153,208 race starters from the Two Oceans Marathon races (2008-2015). All EACs on race day were documented by medical staff. Risk factors associated with EAC investigated included demographics, race distance (21.1 km vs. 56-km), running speed, race experience and race day environmental data (wet-bulb globe temperature [WBGT], humidity, wind speed). Incidence (per 1000 starters; 95% CIs) and incidence ratios (95%CIs) were calculated. RESULTS: The overall incidence of EAC was 1.50 (95% CI: 1.31-1.71). Longer race distance (IR: 2.1; 1.6-2.7; P<0.0001) and slower running speed (IR: 1.3; 1.1-1.5; P=0.0017) were significant risk factors associated with EAC. The incidence of EAC was higher in female vs. male 21.1-km race starters (IR=2.25; 1.47-3.46; P=0.0229). Age and environmental conditions were not associated with EAC (P>0.05) in a cool and temperate environment. CONCLUSIONS: About 1 in 667 race starters (21.1 km and 56-km) develop EAC. Longer race distance, slower running speed and female sex (in 21.1-km starters) are significant risk factors associated with EAC. Race medical directors can identify race entrants that may be at risk of developing EAC, develop prevention strategies and better prepare medical care at these events.

Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor.

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models available, we generated additional cell lines to study these rare cancers. Patient-derived tumors were used to establish 4 new UPS models, including one radiation-associated UPS-UPS271.1, UPS511, UPS0103, and RIS620, one unclassified spindle cell sarcoma-USC060.1, and 3 new models of MPNST-MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing their tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of the cell lines and corresponding xenografts was determined by subcutaneous injection or xenograft re-passaging into immunocompromised mice. USC060.1 and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Targeted sequencing analysis of a panel of genes frequently mutated in sarcomas identified TP53, RB1, and ATRX mutations in a subset of the cell lines. These new cellular models provide the scientific community with powerful tools for detailed studies of tumorigenesis and for investigating novel therapies for UPS and MPNST.

Sex differences associate with late microbiome alterations after murine surgical sepsis.

BACKGROUND: Sepsis-induced gut microbiome alterations contribute to sepsis-related morbidity and mortality. Given evidence for improved postsepsis outcomes in females compared with males, we hypothesized that female mice maintain microbiota resilience versus males. METHODS: Mixed-sex C57BL/6 mice underwent cecal ligation and puncture (CLP) with antibiotics, saline resuscitation, and daily chronic stress and were compared with naive (nonsepsis/no antibiotics) controls. For this work, the results of young (3-5 months) and old (18-22 months) adult mice were analyzed by sex, independent and dependent of age. Mice were sacrificed at days 7 and 14, and 16S rRNA gene sequencing was performed on fecal bacterial DNA. α and ß diversity were determined by Shannon index and Bray-Curtis with principal coordinate analysis, respectively. False discovery rate (FDR) correction was implemented to account for potential housing effect. RESULTS: In control mice, there was no difference in α or ß diversity between male and female mice (FDR, 0.76 and 0.99, respectively). However, male mice that underwent CLP with daily chronic stress had a decrease in microbiota α diversity at 7 days post-CLP (Shannon FDR, 0.005), which was sustained at 14 days post-CLP (Shannon FDR, 0.001), compared with baseline. In addition, male mice maintained differences in ß diversity even at day 14 compared with controls (FDR, <0.0001). In contrast, female mice had a decreased microbiota α diversity (Shannon FDR, 0.03) and ß diversity (FDR, 0.02) 7 days post-CLP but recovered their α and ß diversity by post-CLP day 14 (Shannon FDR, 0.5, and FDR, 0.02, respectively). Further analysis of females revealed that only young female mice were not different (ß diversity) post-CLP day 14 to controls. CONCLUSION: Although sepsis-induced perturbations of the intestinal microbiota occur initially in both male and female C57BL/6 mice, females demonstrate different microbiota by day 14. This may be seen primarily in younger females. This difference in recovery may play a role in outcome differences between sexes after sepsis.

Gla-Rich Protein, Magnesium and Phosphate Associate with Mitral and Aortic Valves Calcification in Diabetic Patients with Moderate CKD.

Accelerated and premature cardiovascular calcification is a hallmark of chronic kidney disease (CKD) patients. Valvular calcification (VC) is a critical indicator of cardiovascular disease and all-cause mortality in this population, lacking validated biomarkers for early diagnosis. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor recently associated with vascular calcification, pulse pressure, mineral metabolism markers and kidney function. Here, we examined the association between GRP serum levels and mitral and aortic valves calcification in a cohort of 80 diabetic patients with CKD stages 2-4. Mitral and aortic valves calcification were detected in 36.2% and 34.4% of the patients and associated with lower GRP levels, even after adjustments for age and gender. In this pilot study, univariate, multivariate and Poisson regression analysis, show that low levels of GRP and magnesium (Mg), and high levels of phosphate (P) are associated with mitral and aortic valves calcification. Receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) values of GRP for mitral (0.762) and aortic (0.802) valves calcification were higher than those of Mg and P. These results suggest that low levels of GRP and Mg, and high levels of P, are independent and cumulative risk factors for VC in this population; the GRP diagnostic value might be potentially useful in cardiovascular risk assessment.