A systematic review and Bayesian meta-analysis assessing intelectin-1 in cancer patients and healthy individuals.

Background: Intelectin-1 (ITLN1) is an adipokine with multiple physiological functions, including a role in tumour formation and development. Previous research reported variable ITLN1 levels for cancer patients and healthy individuals. This study aimed to compare ITLN1 concentrations between controls and cancer patients and to determine the adipokine's physiological level. Methods: Five databases were searched in January 2022 for studies that measured the level of ITLN1 in adults that were healthy or diagnosed with any type of cancer. After title, abstract and full-text screening, the methodological quality of the studies was assessed. The extracted data were meta-analysed using the R language and Bayesian statistical techniques. Results: Overall, 15 studies compared circulating ITLN1 levels between healthy individuals (n=3424) and cancer patients (n=1538), but no differences were observed between these studies. ITLN1 was not different between groups in an analysis that evaluated high-quality studies only (n=5). The meta-analysis indicated considerably higher ITLN1 levels in gastrointestinal (i.e., colorectal, pancreatic, gastric) cancer compared to controls, while the other cancer types did not demonstrate differences between groups. The mean ITLN1 level of healthy individuals was 234 ± 21ng/ml (n=136), while the average value in high-quality studies (n=52) was 257 ± 31ng/ml. Conclusion: Different types of cancer showed different circulating ITLN1 patterns. Circulating ITLN1 concentration was higher in gastrointestinal cancer compared to controls, with strong support from the meta-analytical model. Our analysis also determined the mean ITLN1 level in healthy individuals; this is a crucial starting point for understanding how this cytokine associates with diseases. Two-thirds of the studies were of low methodological quality and thus, future work in this field must focus on improved methods. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=303406, identifier CRD42022303406.

The Use of Biofluid Markers to Evaluate the Consequences of Sport-Related Subconcussive Head Impact Exposure: A Scoping Review.

BACKGROUND: Amidst growing concern about the safety of sport-related repetitive subconcussive head impacts (RSHI), biofluid markers may provide sensitive, informative, and practical assessment of the effects of RSHI exposure. OBJECTIVE: This scoping review aimed to systematically examine the extent, nature, and quality of available evidence from studies investigating the effects of RSHI on biofluid markers, to identify gaps and to formulate guidelines to inform future research. METHODS: PRISMA extension for Scoping Reviews guidelines were adhered to. The protocol was pre-registered through publication. MEDLINE, Scopus, SPORTDiscus, CINAHL, PsycINFO, Cochrane Library, OpenGrey, and two clinical trial registries were searched (until March 30, 2022) using descriptors for subconcussive head impacts, biomarkers, and contact sports. Included studies were assessed for risk of bias and quality. RESULTS: Seventy-nine research publications were included in the review. Forty-nine studies assessed the acute effects, 23 semi-acute and 26 long-term effects of RSHI exposure. The most studied sports were American football, boxing, and soccer, and the most investigated markers were (in descending order): S100 calcium-binding protein beta (S100B), tau, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), phosphorylated tau (p-tau), ubiquitin C-terminal hydrolase L1 (UCH-L1), and hormones. High or moderate bias was found in most studies, and marker-specific conclusions were subject to heterogeneous and limited evidence. Although the evidence is weak, some biofluid markers-such as NfL-appeared to show promise. More markedly, S100B was found to be problematic when evaluating the effects of RSHI in sport. CONCLUSION: Considering the limitations of the evidence base revealed by this first review dedicated to systematically scoping the evidence of biofluid marker levels following RSHI exposure, the field is evidently still in its infancy. As a result, any recommendation and application is premature. Although some markers show promise for the assessment of brain health following RSHI exposure, future large standardized and better-controlled studies are needed to determine biofluid markers' utility.

The Emerging Role of Intelectin-1 in Cancer.

BACKGROUND: Intelectin (ITLN) is an adipokine with two homologs-ITLN1 and ITLN2-that has various physiological functions. Studies analyzing the relationship between ITLN and cancer are focused on ITLN1; the available literature on ITLN2 and cancer is limited. This review aims to evaluate the role of ITLN1 in cancer without imposing any inclusion criteria, to examine pro- and anticancer roles for ITLN1 and to discuss whether the relationship between ITLN and cancer is mediated by obesity. FINDINGS: Overall, ITLN1 level was highly variable in cancer patients but different from healthy individuals. Compared with control groups, patients with gastrointestinal and prostate cancer showed increased concentrations of circulating ITLN1, while patients with gynecological, breast, bladder, and renal cancer had lower ITLN1 levels. Several studies also evaluated tissue and tumor expression of ITLN1. In gastrointestinal cancer, ITLN1 was increased in tumor tissue compared with adjacent healthy tissue and elevated in the visceral adipose tissue of patients compared with controls. Consequently, the high levels of circulating ITLN1 might be determined by the tumor and by the cancer-associated weight loss in gastrointestinal cancer. ITLN1 can activate the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathway. The improper regulation of this pathway may contribute to a series of cellular events that favor tumor development and progression. Obesity has been linked with an increased risk of developing some cancers. Indeed, low circulating ITLN1 levels may be a marker of the metabolic effects of obesity, rather than obesity per se, and might contribute to a deregulation of the PI3K/Akt pathway. CONCLUSIONS: ITLN1 could be associated with cancer formation and progression. Since circulating ITLN1 levels are highly variable and differ between cancer types, the local tumor production of ITLN1 could be more relevant in determining malignant behavior. Future research should aim to identify the source of ITLN1 variability, to understand the differences in ITLN1 between distinct tumor types, and to further explore the signaling pathways through which this adipokine influences cancer biology.

The Reliability of Transcranial Magnetic Stimulation-Derived Corticomotor Inhibition as a Brain Health Evaluation Tool in Soccer Players.

BACKGROUND: The suitability of corticomotor inhibition and corticospinal excitability to measure brain health outcomes and recovery of sport-related head impact (concussion and subconcussion) depends on good inter-day reliability, which is evaluated in this study. Transcranial magnetic stimulation (TMS) reliability in soccer players is assessed by comparing soccer players, for whom reliability on this measure may be reduced due to exposure to head impacts, to generally active individuals not engaged in contact sport. METHODS: TMS-derived corticomotor inhibition and corticospinal excitability were recorded from the rectus femoris muscle during two testing sessions, spaced 1-2 weeks apart in 19 soccer players (SOC-age 22 ± 3 years) and 20 generally active (CON-age 24 ± 4 years) healthy volunteers. Inter-day reliability between the two time points was quantified by using intra-class correlation coefficients (ICC). Intra-group reliability and group differences on actual measurement values were also explored. RESULTS: Good inter-day reliability was evident for corticomotor inhibition (ICCSOC = 0.61; ICCCON = 0.70) and corticospinal excitability (ICCSOC = 0.59; ICCCON = 0.70) in both generally active individuals and soccer players routinely exposed to sport-related head impacts. Corticomotor inhibition showed lower coefficients of variation than excitability for both groups (InhibSOC = 15.2%; InhibCON = 9.7%; ExcitabSOC = 41.6%; ExcitabCON = 39.5%). No group differences between soccer players and generally active individuals were found on the corticomotor inhibition value (p > 0.05), but levels of corticospinal excitability were significantly lower in soccer players (45.1 ± 20.8 vs 85.4 ± 6.2%Mmax, p < 0.0001). Corticomotor inhibition also showed excellent inter-rater reliability (ICC = 0.87). CONCLUSIONS: Corticomotor inhibition and corticospinal excitability are stable and maintain good degrees of reliability when assessed over different days in soccer players, despite their routine exposure to head impacts. However, based on intra-group reliability and group differences of the levels of excitability, we conclude that corticomotor inhibition is best suited for the evaluation of neuromuscular alterations associated with head impacts in contact sports.

Changes in adipose tissue microRNA expression across the menstrual cycle in regularly menstruating females: a pilot study.

Cyclical changes in hormone profiles across the menstrual cycle are associated with alterations in metabolic control. MicroRNAs (miRNAs) contribute to regulating metabolic control, including adipose tissue metabolism. How fluctuations in hormonal profiles across the menstrual cycle affect adipose tissue miRNA expression remains unknown. Eleven healthy, regularly menstruating females underwent four sampling visits across their menstrual cycle. Subcutaneous abdominal adipose tissue and venous blood samples were collected at each sampling visit. Luteinizing hormone (LH) tests, calendar counting, and serum hormone concentrations were used to determine menstrual cycle phases: early-follicular (EF), late-follicular (LF), postovulatory (PO), and midluteal (ML). Serum follicle-stimulating hormone, LH, estrogen, progesterone, and testosterone were determined using multiplex magnetic bead panels and enzyme-linked immunosorbent assays. Global adipose tissue miRNA expression levels were determined via microarray in a subset of participants (n = 8) and 17 candidate miRNAs were validated by RT-qPCR in the whole cohort (n = 11). Global analysis of adipose tissue miRNA expression identified 33 miRNAs significantly altered across the menstrual cycle; however, no significant differences remained after correcting for multiple testing (P > 0.05). RT-qPCR analysis of candidate miRNAs revealed miR-497-5p expression was significantly altered across the menstrual cycle ([Formula: see text] = 0.18, P = 0.03); however, post hoc tests did not reveal any significant differences between menstrual cycle phases (P > 0.05). miR-30c-5p was associated with testosterone concentration (R2 = 0.13, P = 0.033). These pilot data indicate differences in adipose tissue miRNAs in healthy women across the menstrual cycle and a weak association with ovarian hormones. Further research in larger sample sizes is required to confirm regulation of miRNA expression across the menstrual cycle.

Longer Neurophysiological vs. Clinical Recovery Following Sport Concussion.

Objectives: The objective of this study was to assess if injury-related alterations in the Sport Concussion Assessment Tool-5 (SCAT5) are matched by changes in transcranial magnetic stimulation-derived intracortical inhibition. We hypothesised that neurophysiological measures would take longer to return to normal than recovery assessed by the SCAT5 following sport related concussion (SRC). Methods: Thirteen male contact sport athletes (20.5 ± 4.5 years), who reported a concussion were recruited from local Rugby and American football clubs. Participants were tested at 4 timepoints throughout the concussion recovery period: within 24 h of concussion (day 0), and at 7, 9, and 11 days after concussion. All participants completed the SCAT5 and underwent TMS to assess cortical silent period duration (CSp), a measure of intracortical inhibition. Results: After concussion CSp significantly declined from day 0 (122 ± 28 ms) to day 11 (106 ± 15 ms) [F (3, 33) = 7.80, p < 0.001]. SCAT5 measures of symptom number and severity were significantly decreased [symptom number: χ ( 3 ) 2 = 30.44, p < 0.01; symptom severity: χ ( 3 ) 2 = 25.75, p < 0.001] between the day 0 timepoint and each of the other timepoints. SCAT5 balance errors (mBESS) decreased significantly [F (3, 33) = 19.55, p < 0.001] between the day 0 timepoint and each of the other timepoints. CSp and SCAT5 recovery patterns were different. SCAT5 domains recovered faster showing no further significant changes after day 7, whilst CSp was still decreasing between days 7 and 9. Due to the small sample size we also used a Bayesian linear model to investigate the recovery of CSp and mBESS. The posterior distribution of our Bayesian model provided evidence that CSp decreased at day 7 and it continued to decrease at day 9, unlike mBESS which decreased at day 7 and then reached a plateau. Conclusion: There are clinically important discrepancies between clinical and neurophysiological measures of concussion recovery. This finding has important implications for return to play (RTP) protocols and the prevention of complications after sport concussion.

Human Subcutaneous Adipose Tissue Sampling using a Mini-liposuction Technique.

Studies on adipose tissue are useful in understanding metabolic and other conditions. Human subcutaneous adipose tissue is accessible. With appropriate training and strict adherence to aseptic technique, subcutaneous adipose samples can be safely and efficiently obtained in a non-clinical setting by researchers. Following the administration of local anesthetic lateral to the umbilicus, a 14 G needle attached to a 5 or 10 mL syringe is inserted through the skin into the subcutaneous tissue. Under suction, the syringe is moved in a reciprocating, slicing motion to isolate fragments of adipose tissue. Withdrawing the plunger is enough to ensure that adipose tissue fragments are aspirated through the needle into the syringe. A single biopsy can collect about 200 mg of tissue. This biopsy technique is very safe for both participants and research staff. Following the biopsy, participants can resume most everyday activities, although they should avoid swimming and overly strenuous activities for 48 h to avoid excessive bleeding. Participants can safely undergo 2 biopsies within a single day, meaning that the technique can be applied in before-after acute intervention studies.

Hill Runner's Physiology, Performance and Nutrition: A Descriptive Study.

Objectives: The aim of this descriptive study was to characterise anthropometric variables, aerobic capacity, running performance and energy intake and expenditure of hill runners in free-living conditions, and to investigate the relationship between age, anthropometric variables, aerobic capacity and running performance. Methods: Twenty-eight hill runners participated in this study (17 males and 11 females; aged 18-65 years). Body fat percentage estimate, sum of eight skinfolds (triceps, subscapular, biceps, iliac crest, supraspinale, abdominal, front thigh and medial calf) and maximal oxygen capacity (VO2max) were assessed in a laboratory setting. Participants also completed a timed hill run (Dumyat Hill, Scotland, ascent: 420 m, distance: 8 km) while wearing a portable gas analyzer to assess oxygen consumption (VO2). Energy intake and energy expenditure were assessed in free-living conditions over three consecutive days different from the testing days through self-reported food diaries and accelerometers. Results: VO2max assessed in the lab (51.2 ± 7.6 ml·min-1·kg-1) showed a weak negative relationship with age [rs(23) = -0.38, p = 0.08]. Neither body fat percentage (median 12.4; IQR 10.1-17.1) nor the sum of skinfolds (median 81.8; IQR 62.4-97.8 mm) correlated with age [rs(28) = 0.001, p = 0.10 and 26 rs(28) = -0.02, p = 0.94, respectively]. The observed intensity of the hill run was 89 ± 6% of the age predicted maximum heart rate and 87 ± 9% of the VO2max observed in the lab. Hill running performance correlated with VO2max [r(21) = 0.76, p < 0.001], age [rs(26) = -0.44, p = 0.02] and with estimated body fat percentage and sum of skinfolds [rs(26) = -0.66, p < 0.001 and rs(26) = -0.49, p = 0.01, respectively]. Energy intake negatively correlated with age [rs(26) = -0.43, p = 0.03], with the overall energy intake being significantly lower than the total energy expenditure (2273 ± 550 vs. 2879 ± 510 kcal·day-1; p < 0.001; d = 1.05). Conclusion: This study demonstrated that hill running performance is positively associated with greater aerobic capacity and negatively associated with increases in adiposity and age. Further, the study highlights that hill runners are at risk of negative energy balance.

Effects of sport-related repetitive subconcussive head impacts on biofluid markers: a scoping review protocol.

INTRODUCTION: Sport-related repetitive subconcussive head impacts (RSHIs) are increasingly thought to be associated with adverse long-term outcomes. However, owing to potentially subtle effects, accurate assessment of harm to the brain as a consequence of RSHI is a major challenge and an unmet need. Several studies suggest that biofluid markers can be valuable objective tools to aid the diagnosis and injury characterisation and help in medical decision-making. Still, by and large, the results have been limited, heterogeneous and inconsistent. The main aims of this scoping review are therefore (1) to systematically examine the extent, nature and quality of available evidence from studies investigating effects of RSHI on fluid biomarkers and (2) to formulate guidelines and identify gaps with the aim to inform future clinical studies and the development of research priorities. METHODS AND ANALYSES: We will use a comprehensive search strategy to retrieve all available and relevant articles in the literature. The following electronic databases will be systematically searched: MEDLINE (EBSCO host; from 1809 to 2020); Scopus (from 1788 to 2020); SPORTDiscus (from 1892 to 2020); CINAHL Complete (from 1937 to 2020); PsycINFO (from 1887 to 2020); Cochrane Library (to 2020); OpenGrey (to 2020); ClinicalTrials.gov (to 2020) and WHO International Clinical Trials Registry Platform (to 2020). We will consider primarily biomedical studies evaluating the biofluid markers following RSHI. Two independent reviewers will screen articles for inclusion using predefined eligibility criteria and extract data of retained articles. Disagreements will be resolved through consensus or arbitrated by a third reviewer if necessary. Data will be reported qualitatively given the heterogeneity of the included studies. In synthesising the evidence, we will structure results by markers, sample types, outcomes, sport and timepoints. ETHICS AND DISSEMINATION: Ethics approval is not required. We will submit results for peer-review publication, and present at relevant conferences.

Understanding the Consequences of Repetitive Subconcussive Head Impacts in Sport: Brain Changes and Dampened Motor Control Are Seen After Boxing Practice.

OBJECTIVES: The potential effects of exposure to repetitive subconcussive head impacts through routine participation in sport are not understood. To investigate the effects of repetitive subconcussive head impacts we studied boxers following customary training (sparring) using transcranial magnetic stimulation (TMS), decomposition electromyographic (EMG) and tests of memory. METHODS: Twenty amateur boxers performed three 3-min sparring bouts. Parameters of brain function and motor control were assessed prior to sparring and again immediately, 1 h and 24 h post-sparring. Twenty control participants were assessed following mock-sparring. RESULTS: One hour after sparring boxers showed increased corticomotor inhibition, altered motor unit recruitment strategies, and decreased memory performance relative to controls, with values returning to baseline by the 24 h follow up. CONCLUSION: Repetitive subconcussive head impacts associated with sparring resulted in acute and transient brain changes similar to those previously reported in soccer heading, providing convergent evidence that sport-related head impacts produce a GABAergic response. These acute changes in brain health are reminiscent of effects seen following brain injury, and suggest a potential mechanism underlying the damaging long-term effects of routine repetitive head impacts in sport.

Influence of the "Slingshot" Bench Press Training Aid on Bench Press Kinematics and Neuromuscular Activity in Competitive Powerlifters.

Dugdale, JH, Hunter, AM, Di Virgilio, TG, Macgregor, LJ, and Hamilton, DL. Influence of the "Slingshot" bench press training aid on bench press kinematics and neuromuscular activity in competitive powerlifters. J Strength Cond Res 33(2): 327-336, 2019-This study examined the acute effects of the "Slingshot" (SS) on bench press performance, prime mover surface electromyographic (sEMG) amplitude, and barbell velocity during maximal and submaximal bench pressing in competitive male powerlifters. Fifteen male powerlifters (mean ± SD; age: 27.05 ± 5.94 years; mass: 94.15 ± 13.43 kg; 1 repetition maximum [1RM] bench press: 139.7 ± 16.79 kg) participated in the study. Bench press strength, average barbell velocity, and sEMG amplitude of the prime mover muscles (triceps brachii, pectoralis major, and anterior deltoid) were measured during 2 conditions; "Raw" (without use of any assistance) and "SS" (using the "Slingshot" to perform both the weight achieved during "Raw" 1RM testing [Raw max/SS], and absolute 1RM using the "SS"). The results showed that the "SS" significantly increased bench press 1RM performance by a mean ± SD of 20.67 ± 3.4 kg. Barbell velocity and stick point analysis indicate that this improvement is likely driven by an increase in peak and prestick barbell velocity as triceps root mean square (RMS) was lower throughout all rep max phases with the "SS." The "SS" also caused reductions in RMS, specifically of the triceps at all rep ranges but barbell velocity was better maintained in the last reps of all sets. These data indicate that the "SS" specifically deloaded the triceps muscle throughout all rep ranges and provide assistance to maintaining barbell velocity under fatigue during later repetitions of multiple repetition sets. The "SS" training aid could therefore be used in deload phases of bench press training or as an overreaching and velocity training aid.

Evidence for Acute Electrophysiological and Cognitive Changes Following Routine Soccer Heading.

INTRODUCTION: There is growing concern around the effects of concussion and sub-concussive impacts in sport. Routine game-play in soccer involves intentional and repeated head impacts through ball heading. Although heading is frequently cited as a risk to brain health, little data exist regarding the consequences of this activity. This study aims to assess the immediate outcomes of routine football heading using direct and sensitive measures of brain function. METHODS: Nineteen amateur football players (5 females; age 22±3y) headed machine-projected soccer balls at standardized speeds, modelling routine soccer practice. The primary outcome measure of corticomotor inhibition measured using transcranial magnetic stimulation, was assessed prior to heading and repeated immediately, 24h, 48h and 2weeks post-heading. Secondary outcome measures were cortical excitability, postural control, and cognitive function. RESULTS: Immediately following heading an increase in corticomotor inhibition was detected; further to these electrophysiological alterations, measurable reduction memory function were also found. These acute changes appear transient, with values normalizing 24h post-heading. DISCUSSION: Sub-concussive head impacts routine in soccer heading are associated with immediate, measurable electrophysiological and cognitive impairments. Although these changes in brain function were transient, these effects may signal direct consequences of routine soccer heading on (long-term) brain health which requires further study.