IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance.

The cytokine interleukin-6 (IL-6) is involved in a diverse set of physiological processes. Traditionally, IL-6 has been thought of in terms of its inflammatory actions during the acute phase response and in chronic conditions such as rheumatoid arthritis and obesity. However, IL-6 is also an important signaling molecule during exercise, being acutely released from working muscle fibers with increased exercise duration, intensity, and muscle glycogen depletion. In this context, IL-6 enables muscle-organ crosstalk, facilitating a coordinated response to help maintain muscle energy homeostasis, while also having anti-inflammatory actions. The range of actions of IL-6 can be explained by its dichotomous signaling pathways. Classical signaling involves IL-6 binding to a cell-surface receptor (mbIL-6R; present on only a small number of cell types) and is the predominant signaling mechanism during exercise. Trans-signaling involves IL-6 binding to a soluble version of its receptor (sIL-6R), with the resulting complex having a much greater half-life and the ability to signal in all cell types. Trans-signaling drives the inflammatory actions of IL-6 and is the predominant pathway in disease. A single nucleotide polymorphism (rs2228145) on the IL-6R gene can modify the classical/trans-signaling balance through increasing the levels of sIL-6R. This SNP has clinical significance, having been linked to inflammatory conditions such as rheumatoid arthritis and type 1 diabetes, as well as to the severity of symptoms experienced with COVID-19. This review will describe how acute exercise, chronic training and the rs2228145 SNP can modify the IL-6 signaling pathway and the consequent implications for health and athletic performance.

The race for space: Modelling the landward migration of coastal wetlands under sea level rise at regional scale.

Globally, sea-level rise (SLR) is a major environmental challenge for coastal ecosystems. Of particular concern are the impacts on intertidal wetlands, the loss of which would have detrimental consequences for both human and ecological communities. On the south-east Australian coast, case studies suggest that the future of intertidal wetlands will greatly depend on landward migration as surface accretion may not keep up with the predicted SLR in many estuaries. However, due to differences in geomorphological settings and land-use, estuaries vary in their capacity to accommodate lateral migration. Regional scale assessment of the lateral accommodation space is therefore critical for pre-emptive planning to conserve these valuable coastal ecosystems. In this study, we analysed wetland lateral accommodation space distribution within 110 estuaries under three SLR scenarios and three land management options on the New South Wales coast, south-east Australia. From the wetland distribution predictions, we calculated and mapped the lateral accommodation space in each estuary associated with each sea level and land use scenario. We further investigated the relationships between wetland migration capacity, intertidal hypsometry represented by elevation skewness, and estuary type within a Bayesian analysis framework. Our results showed that while a few large riverine estuaries dominated the state's total accommodation space, saline wetlands were at risk of disappearing from most intermittently closed-open estuaries if they cannot vertically accrete at the pace of SLR. These distinct responses to SLR are due to different elevation distributions. Furthermore, our assessment of land use adaptation options suggested that the promotion of landward migration without impairing other important ecosystems could be achieved by making low intensity land uses available within several riverine estuaries and barrier (open entrance) estuaries. Through identifying migration opportunities and barriers, the findings of the study could support regional scale adaptation strategies to ensure the sustainability of wetland-associated ecosystem goods and services.

Baseline predictive factors for foregut and hindgut response to long-term gastric electrical stimulation using augmented energy.

INTRODUCTION: Gastric electrical stimulation (GES) has been recommended for drug refractory patients with gastroparesis, but no clear baseline predictors of symptom response exist. We hypothesized that long-term predictors to GES for foregut and hindgut symptoms exist, particularly when using augmented energies. PATIENTS: We evaluated 307 patients at baseline, 1 week post temporary GES, and one year after permanent GES. Baseline measures included upper and lower symptoms by patient-reported outcomes (PRO), solid and liquid gastric emptying (GET), cutaneous, mucosal, and serosal electrophysiology (EGG, m/s EG), BMI, and response to temporary stimulation. METHODS: Foregut and hindgut PRO symptoms were analyzed for 12-month patient outcomes. All patients utilized a standardized energy algorithm with the majority of patients receiving medium energy at 12 months. Patients were categorized based on change in average GI symptom scores at the time of permanent GES compared to baseline using a 10% decrease over time as the cutoff between improvers versus non-improvers. RESULTS: By permanent GES implant, average foregut and hindgut GI symptom scores reduced 42% in improved patients (n = 199) and increased 27% in non-improved patients (n = 108). Low BMI, baseline infrequent urination score, mucosal EG ratio, and proximal mucosal EG low-resolution amplitude remained significant factors for improvement status. CONCLUSIONS: GES, for patients responding positively, improved both upper/foregut and lower/hindgut symptoms with most patients utilizing higher than nominal energies. Low baseline BMI and the presence of infrequent urination along with baseline gastric electrophysiology may help identify those patients with the best response to GES/bio-electric neuromodulation.

Attrition and reenlistment in the Army: Using the Tailored Adaptive Personality Assessment System (TAPAS) to improve retention.

Attrition and reenlistment are critical outcomes that continually shape the Army's workforce. However, relatively little is known about factors that reliably predict which Soldiers will ultimately complete their first term of service or reenlist after their first term has concluded. The present study evaluated the efficacy of a noncognitive measure, the Tailored Adaptive Personality Assessment System (TAPAS), as well as a traditional cognitive test, the Armed Forces Qualification Test (AFQT), as predictors of attrition and reenlistment. Specific categories of attrition were examined based on the reasons Soldiers separated from the Army, both during training and while the Soldiers were in their units. Additionally, analyses were conducted to model attrition over time, and reenlistment was examined both Army-wide and for specific MOS. The paper concludes with a discussion of the findings and needs for future research concerning the potential value of cognitive and noncognitive measures for better understanding and predicting Army attrition and reenlistment.

A Study on the Effect of Patient Characteristics, Geographical Utilization, and Patient Outcomes for Total Pancreatectomy Alone and Total Pancreatectomy With Islet Autotransplantation in Patients With Pancreatitis in the United States.

OBJECTIVES: A selective therapy for pancreatitis is total pancreatectomy and islet autotransplantation. Outcomes and geographical variability of patients who had total pancreatectomy (TP) alone or total pancreatectomy with islet autotransplantation (TPIAT) were assessed. METHODS: Data were obtained from the Healthcare Cost and Utilization Project National Inpatient Sample database. Weighed univariate and multivariate analyses were performed to determine the effect of measured variables on outcomes. RESULTS: Between 2002 and 2013, there were 1006 TP and 825 TPIAT in patients with a diagnosis of chronic pancreatitis, and 1705 TP and 830 TPIAT for any diagnosis of pancreatitis. The majority of the TP and TPIAT were performed in larger urban hospitals. Costs were similar for TP and TPIAT for chronic pancreatitis but were lower for TPIAT compared with TP for any type of pancreatitis. The trend for TP and TPIAT was significant in all geographical areas during the study period. CONCLUSIONS: There is an increasing trend of both TP and TPIAT. Certain groups are more likely to be offered TPIAT compared with TP alone. More data are needed to understand disparities and barriers to TPIAT, and long-term outcomes of TPIAT such as pain control and glucose intolerance need further study.

Lower-Limb Stiffness and Maximal Sprint Speed in 11-16-Year-Old Boys.

Meyers, RW, Moeskops, S, Oliver, JL, Hughes, MG, Cronin, JB, and Lloyd, RS. Lower-limb stiffness and maximal sprint speed in 11-16-year-old boys. J Strength Cond Res 33(7): 1987-1995, 2019-The purpose of the study was to examine the relationship between vertical stiffness, leg stiffness, and maximal sprint speed in a large cohort of 11-16-year-old boys. Three-hundred thirty-six boys undertook a 30-m sprint test using a floor-level optical measurement system, positioned in the final 15-m section. Measures of speed, step length, step frequency, contact time, and flight time were directly measured while force, displacement, vertical stiffness, and leg stiffness, were modeled from contact and flight times, from the 2 fastest consecutive steps for each participant over 2 trials. All force, displacement, and stiffness variables were significantly correlated with maximal sprint speed (p ≤ 0.05). Relative vertical stiffness had a very large (r > 0.7) relationship with sprint speed, whereas vertical center of mass displacement, absolute vertical stiffness, relative peak force, and maximal leg spring displacement had large (r > 0.5) relationships. Relative vertical stiffness and relative peak force did not significantly change with advancing age (p > 0.05), but together with maximal leg spring displacement accounted for 96% of the variance in maximal speed. It seems that relative vertical stiffness and relative peak force are important determinants of sprint speed in boys aged 11-16 years, but are qualities that may need to be trained because of no apparent increases from natural development. Practitioners may wish to use training modalities such as plyometrics and resistance training to enable adaptation to these qualities because of their importance as predictors of speed in youth.

Ductal Cell Reprogramming to Insulin-Producing Beta-Like Cells as a Potential Beta Cell Replacement Source for Chronic Pancreatitis.

Islet cell auto-transplantation is a novel strategy for maintaining blood glucose levels and improving the quality of life in patients with chronic pancreatitis (CP). Despite the many recent advances associated with this therapy, obtaining a good yield of islet infusate still remains a pressing challenge. Reprogramming technology, by making use of the pancreatic exocrine compartment, can open the possibility of generating novel insulin-producing cells. Several lineage-tracing studies present evidence that exocrine cells undergo dedifferentiation into a progenitor-like state from which they can be manipulated to form insulin-producing cells. This review will present an overview of recent reports that demonstrate the potential of utilizing pancreatic ductal cells (PDCs) for reprogramming into insulin- producing cells, focusing on the recent advances and the conflicting views. A large pool of ductal cells is released along with islets during the human islet isolation process, but these cells are separated from the pure islets during the purification process. By identifying and improving existing ductal cell culture methods and developing a better understanding of mechanisms by which these cells can be manipulated to form hormone-producing islet-like cells, PDCs could prove to be a strong clinical tool in providing an alternative beta cell source, thus helping CP patients maintain their long-term glucose levels.

Improved recovery of human islets from young donor pancreases utilizing increased protease dose to collagenase for digesting peri-islet extracellular matrix.

Human islet isolation from young donor pancreases (YDP) utilizing the current purified standard dose of collagenase-protease enzyme mixtures often results in the release of a high percentage of mantled islets. Mantled islets are those surrounded by exocrine tissue and are difficult to purify by density gradient centrifugation, leading to poor islet recovery. Based on difference in extracellular matrix, and total collagen content between YDP and old donor pancreas (ODP, > 35 Y) led us to compare results from islet isolation using increased collagenase combination (ICC) or increased protease combination (IPC), to the standard enzyme combination (SEC) in a "trisected" pancreas model to overcome the donor-to-donor variability. These results showed a reduced percentage of mantled islets (17% ± 7.5%) and higher postpurification islet recovery (83.8% ± 5.6%) with IPC. Furthermore, these results were confirmed in 13 consecutive whole pancreas islet isolations utilizing IPC from VitaCyte, Roche, or SERVA collagenase-protease enzyme mixtures. Results obtained from in vitro and in vivo islet functional assessment indicated that islets isolated using IPC retained normal islet morphology, insulin secretion, and the ability to reverse diabetes after transplantation in diabetic nude mice. This is the first report utilizing trisected pancreas to assess the effectiveness of different enzyme combinations to improve islet recovery from young donor pancreases.

Endothelial cell regulation through epigenetic mechanisms: Depicting parallels and its clinical application within an intra-islet microenvironment.

The intra-islet endothelial cells (ECs), the building blocks of islet microvasculature, govern a number of cellular and pathophysiological processes associated with the pancreatic tissue. These cells are key to the angiogenic process and essential for islet revascularization after transplantation. Understanding fundamental mechanisms by which ECs regulate the angiogenic process is important as these cells maintain and regulate the intra-islet environment facilitated by a complex signaling crosstalk with the surrounding endocrine cells. In recent years, many studies have demonstrated the impact of epigenetic regulation on islet cell development and function. This review will present an overview of the reports involving endothelial epigenetic mechanisms particularly focusing on histone modifications which have been identified to play a critical role in governing EC functions by modifying the chromatin structure. A better understanding of epigenetic mechanisms by which these cells regulate gene expression and function to orchestrate cellular physiology and pathology is likely to offer improved insights on the functioning and regulation of an intra-islet endothelial microvascular environment.

Beneficial effect of recombinant rC1rC2 collagenases on human islet function: Efficacy of low-dose enzymes on pancreas digestion and yield.

A high number of human islets can be isolated by using modern purified tissue dissociation enzymes; however, this requires the use of >20 Wunsch units (WU)/g of pancreas for digestion. Attempts to reduce this dose have resulted in pancreas underdigestion and poor islet recovery but improved islet function. In this study, we achieved a high number of functional islets using a low dose of recombinant collagenase enzyme mixture (RCEM-1200 WU rC2 and 10 million collagen-degrading activity [CDA] U of rC1 containing about 209 mg of collagenase to digest a 100-g pancreas). The collagenase dose used in these isolations is about 42% of the natural collagenase enzyme mixture (NCEM) dose commonly used to digest a 100-g pancreas. Low-dose RCEM was efficient in digesting entire pancreases to obtain higher yield (5535 ± 830 and 2582 ± 925 islet equivalent/g, P < .05) and less undigested tissue (16.7 ± 5% and 37.8 ± 3%, P < .05) compared with low-dose NCEM (12WU/g). Additionally, low-dose RCEM islets retained better morphology (confirmed with scanning electron microscopy) and higher in vitro basal insulin release (2391 ± 1342 and 1778 ± 978 µU/mL; P < .05) compared with standard-dose NCEM. Nude mouse bioassay demonstrated better islet function for low-dose RCEM (area under the curve [AUC] 24 968) compared with low-dose (AUC-38 225) or standard-dose NCEM (AUC-38 685), P < .05. This is the first report indicating that islet function can be improved by using low-dose rC1rC2 (RCEM).

The Ability of Exercise-Associated Oxidative Stress to Trigger Redox-Sensitive Signalling Responses.

In this review, we discuss exercise as an oxidative stressor, and elucidate the mechanisms and downstream consequences of exercise-induced oxidative stress. Reactive oxygen species (ROS) are generated in the mitochondria of contracting skeletal myocytes; also, their diffusion across the myocyte membrane allows their transport to neighbouring muscle tissue and to other regions of the body. Although very intense exercise can induce oxidative damage within myocytes, the magnitudes of moderate-intensity exercise-associated increases in ROS are quite modest (~two-fold increases in intracellular and extracellular ROS concentrations during exercise), and so the effects of such increases are likely to involve redox-sensitive signalling effects rather than oxidative damage. Therefore, the responses of muscle and non-muscle cells to exercise-associated redox-sensitive signalling effects will be reviewed; for example, transcription factors such as Peroxisome Proliferator Activated Receptor-gamma (PPARγ) and Liver X-Receptor-alpha (LXRα) comprise redox-activable signalling systems, and we and others have reported exercise-associated modulation of PPARγ and/or LXRα-regulated genes in skeletal myocyte and in non-muscle cell-types such as monocyte-macrophages. Finally, the consequences of such responses in the context of management of chronic inflammatory conditions, and also their implications for the design of exercise training programmes (particularly the use of dietary antioxidants alongside exercise), will be discussed.

Pig islet xenotransplantation.

PURPOSE OF REVIEW: The current article reviews the rationale, sources and preparation of pig islets for xenotransplantation, and presents current progress in solving the problems associated with establishing pig islet transplant as a clinical treatment for type 1 diabetes. SUMMARY: Islet transplantation is an effective treatment option for type 1 diabetes, but the available supply of human pancreases is insufficient to meet the need and demand for obtaining islets. Pig islets provide a readily available source for islet transplantation, with trials in non-human primates demonstrating their potential to reverse diabetes. The risk of zoonosis can be reduced by designated pathogen-free breeding of the donor pigs, but porcine endogenous retroviruses (PERVs) that are integrated into the genome of all pigs are especially difficult to eliminate. However, clinical trials have demonstrated an absence of PERV transmission with a significant reduction in the number of severe hypoglycemic episodes and up to 30% reduction in exogenous insulin doses. A number of methods such as production of various transgenic pigs to better xenotransplantation efficiency and the encapsulation of islets to isolate them from the host immune system are currently being tested to overcome the xenograft immune rejection. Furthermore, ongoing research is also shedding light on factors such as the age and breed of the donor pig to determine the optimal islet quantity and function.

Rate of hepatitis C viral clearance by human livers in human patients: Liver transplantation modeling primary infection and implications for studying entry inhibition.

To better understand the dynamics of early hepatitis C virus (HCV) infection, we determined how rapidly non-cirrhotic HCV-uninfected liver allografts clear HCV from the circulation of cirrhotic HCV-infected patients at the time of transplantation but before administration of immunosuppression. Specifically, we characterized serum HCV kinetics during the first 90 min of reperfusion for 19 chronically HCV-infected patients transplanted with an HCV-uninfected liver by measuring serum viral load immediately prior to reperfusion (t = 0) and then every 15 min for a total of 90 min (t = 90). Immunosuppression was withheld until all samples were taken to better model primary infection. During this period, rates of viral clearance varied more than 20-fold with a median rate constant of 0.0357 1/min, range 0.0089-0.2169; half-life (minutes) median 19.4, range 3.2-77.8. The majority of viral clearance occurred within the first 60 min. The amount of blood transfused during this 90-min period (a potential confounding variable of this human liver transplant model of primary infection) accounted for 53% and 59% of k (r = 0.53, p = 0.05) and half-life (r = 0.59, p = 0.03) variability, respectively. No other clinical variables tested (age, allograft weight, and degree of reperfusion injury as assessed by peak postoperative ALT or AST) accounted for the remaining variability (p>0.05). CONCLUSION: In a human liver transplant model of primary infection, HCV rapidly clears the bloodstream. With approximately 90% of clearance occurring in the first 90 minutes of reperfusion, studies of HCV entry inhibition could utilize rate of clearance during this early period as an outcome measure.

Intra-islet endothelial cell and ß-cell crosstalk: Implication for islet cell transplantation.

The intra-islet microvasculature is a critical interface between the blood and islet endocrine cells governing a number of cellular and pathophysiological processes associated with the pancreatic tissue. A growing body of evidence indicates a strong functional and physical interdependency of ß-cells with endothelial cells (ECs), the building blocks of islet microvasculature. Intra-islet ECs, actively regulate vascular permeability and appear to play a role in fine-tuning blood glucose sensing and regulation. These cells also tend to behave as "guardians", controlling the expression and movement of a number of important immune mediators, thereby strongly contributing to the physiology of islets. This review will focus on the molecular signalling and crosstalk between the intra-islet ECs and ß-cells and how their relationship can be a potential target for intervention strategies in islet pathology and islet transplantation.

sIL-6R Is Related to Weekly Training Mileage and Psychological Well-being in Athletes.

INTRODUCTION: Interleukin 6 (IL-6) has been ascribed both positive and negative roles in the context of exercise and training. The dichotomous nature of IL-6 signaling seems to be determined by the respective concentration of its receptors (both membrane-bound [IL-6R] and soluble [sIL-6R] forms). The purpose of the present study was to investigate the response of sIL-6R to long-term training and to investigate the relationship between sIL-6R, self-reported measures of well-being, and upper respiratory symptoms in highly trained endurance athletes. METHODS: Twenty-nine athletes provided resting blood samples and completed well-being and illness monitoring questionnaires on a weekly basis for a period of 18 wk during a winter training block. RESULTS: Upper respiratory symptoms were not correlated to concentrations of sIL-6R or cortisol, but there was a nonsignificant trend (P = 0.08) for the most illness-prone athletes (as defined by self-reported illness questionnaire data) to exhibit higher average sIL-6R concentrations compared with the least ill (23.7 ± 4.3 vs 20.1 ± 3.8 ng·mL). Concentrations of sIL-6R were positively correlated to subjective measures of stress (r = 0.64, P = 0.004) and mood (r = 0.49, P = 0.02) but were negatively correlated to sleep quality (r = -0.43, P = 0.05) and cortisol concentration (r = -0.17, P = 0.04). In a subgroup of 10 athletes, weekly training distance was quantified by coaching staff, and this negatively correlated with sIL-6R in the following week (r = -0.74, P < 0.005). CONCLUSION: The findings of the current study suggest that sIL-6R is responsive to prolonged periods of exercise training, with sIL-6R levels varying related to the volume of training performed in the preceding week. Importantly, our data indicate that changes in sIL-6R levels could be linked to common symptoms of overreaching, such as high levels of stress, and/or depressed mood.

Asymmetry During Maximal Sprint Performance in 11- to 16-Year-Old Boys.

PURPOSE: The aim of this study was to examine the influence of age and maturation upon magnitude of asymmetry in the force, stiffness and the spatiotemporal determinants of maximal sprint speed in a large cohort of boys. METHODS: 344 boys between the ages of 11 and 16 years completed an anthropometric assessment and a 35 m sprint test, during which sprint performance was recorded via a ground-level optical measurement system. Maximal sprint velocity, as well as asymmetry in spatiotemporal variables, modeled force and stiffness data were established for each participant. For analysis, participants were grouped into chronological age, maturation and percentile groups. RESULTS: The range of mean asymmetry across age groups and variables was 2.3-12.6%. The magnitude of asymmetry in all the sprint variables was not significantly different across age and maturation groups (p > .05), except relative leg stiffness (p < .05). No strong relationships between asymmetry in sprint variables and maximal sprint velocity were evident (rs < .39). CONCLUSION: These results provide a novel benchmark for the expected magnitude of asymmetry in a large cohort of uninjured boys during maximal sprint performance. Asymmetry in sprint performance is largely unaffected by age or maturation and no strong relationships exist between the magnitude of asymmetry and maximal sprint velocity.

Influence of Age, Maturity, and Body Size on the Spatiotemporal Determinants of Maximal Sprint Speed in Boys.

Meyers, RW, Oliver, JL, Hughes, MG, Lloyd, RS, and Cronin, JB. Influence of age, maturity, and body size on the spatiotemporal determinants of maximal sprint speed in boys. J Strength Cond Res 31(4): 1009-1016, 2017-The aim of this study was to investigate the influence of age, maturity, and body size on the spatiotemporal determinants of maximal sprint speed in boys. Three-hundred and seventy-five boys (age: 13.0 ± 1.3 years) completed a 30-m sprint test, during which maximal speed, step length, step frequency, contact time, and flight time were recorded using an optical measurement system. Body mass, height, leg length, and a maturity offset represented somatic variables. Step frequency accounted for the highest proportion of variance in speed (∼58%) in the pre-peak height velocity (pre-PHV) group, whereas step length explained the majority of the variance in speed (∼54%) in the post-PHV group. In the pre-PHV group, mass was negatively related to speed, step length, step frequency, and contact time; however, measures of stature had a positive influence on speed and step length yet a negative influence on step frequency. Speed and step length were also negatively influence by mass in the post-PHV group, whereas leg length continued to positively influence step length. The results highlighted that pre-PHV boys may be deemed step frequency reliant, whereas those post-PHV boys may be marginally step length reliant. Furthermore, the negative influence of body mass, both pre-PHV and post-PHV, suggests that training to optimize sprint performance in youth should include methods such as plyometric and strength training, where a high neuromuscular focus and the development force production relative to body weight are key foci.

Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation.

UNLABELLED: Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation. METHODS: We used a factorial approach to evaluate the effect of high and low target activities of recombinant class I (rC1) and class II (rC2) collagenase on human islet yield. Consequently, 4 different enzyme formulations with divergent C1:C2 collagenase mass ratios were assessed, each supplemented with the same dose of neutral protease. Both split pancreas and whole pancreas models were used to test enzyme targets (n = 20). Islet yield/g pancreas was compared with historical enzymes (n = 42). RESULTS: Varying the Wunsch (rC2) and collagen degradation activity (CDA, rC1) target dose, and consequently the C1:C2 mass ratio, had no significant effect on tissue digestion. Digestions using higher doses of Wunsch and CDA resulted in comparable islet yields to those obtained with 60% and 50% of those activities, respectively. Factorial analysis revealed no significant main effect of Wunsch activity or CDA for any parameter measured. Aggregate results from 4 different collagenase formulations gave 44% higher islet yield (>5000 islet equivalents/g) in the body/tail of the pancreas (n = 12) when compared with those from the same segment using a standard natural collagenase/protease mixture (n = 6). Additionally, islet yields greater than 5000 islet equivalents/g pancreas were also obtained in whole human pancreas. CONCLUSIONS: A broader C1:C2 ratio can be used for human islet isolation than has been used in the past. Recombinant collagenase is an effective replacement for the natural enzyme and we have determined that high islet yield can be obtained even with low doses of rC1:rC2, which is beneficial for the survival of islets.

The Influence of Maturation on Sprint Performance in Boys over a 21-Month Period.

PURPOSE: This study examined how the characteristics of maximal overground sprint performance are affected by the period of peak height velocity (PHV) in boys. METHODS: One hundred eighty-nine school-age boys completed two assessments of maximal sprint performance, separated by a 21-month period. Kinematic characteristics of sprint performance were collected during a 30-m sprint using a floor-level optical measurement system, with modeled force and stiffness characteristics also calculated. Participants were grouped according to maturation using a noninvasive predictive equation. Individuals whose maturity offset was <-0.5 yr in both assessments were classed as "pre-PHV" (n = 67), whereas those whose maturity offset developed from <-0.5 to >0.5 yr in test two were classed as "pre-to-post PHV" (n = 39). Participants with a maturity offset between >-0.5 and <0.5 yr at test 2 were removed from analysis (n = 67) to ensure that the entire pre-to-post-PHV group had experienced the PHV spurt. RESULTS: The pre-to-post-PHV group experienced significantly greater increases in speed (10.4% vs 5.6%) and relative vertical stiffness (12.1% vs 5.6%) compared with the pre-PHV group. Step frequency declined (-2.4%) and contact time increased (2.3%) in the pre-PHV group, whereas step frequency increased (2.7%) and contact time decreased (-3.6%) in the pre-PHV to post-PHV group. Changes in relative measures of vertical stiffness, maximal force, and leg stiffness accounted for 79% and 83% of the changes in speed between assessments for pre-PHV and pre-to-post-PHV groups, respectively. CONCLUSIONS: As boys experience PHV, there are greater increases in maximal sprint speed compared with those who remain pre-PHV. Furthermore, measures of relative stiffness and relative maximal force appear to exert an important influence on the development of maximal sprint speed in boys, regardless of maturity.

Interleukin-6 and associated cytokine responses to an acute bout of high-intensity interval exercise: the effect of exercise intensity and volume.

Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL-10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6-related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 ± 1.51) than LOW (1.40 ± 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise.