Effects of Resistance and Endurance Training Alone or Combined on Hormonal Adaptations and Cytokines in Healthy Children and Adolescents: A Systematic Review and Meta-analysis.

BACKGROUND: No previous systematic review has quantitatively compared the effects of resistance training, endurance training, or concurrent training on hormonal adaptations in children and adolescents. Objective was to examine the effects of exercise training and training type on hormonal adaptations in children and adolescents. METHODS: A systematic literature search was conducted in the following databases: PubMed, Web of Science, and EBSCO. Eligibility criteria were: population: healthy youth population sample (mean age < 18 years); intervention: resistance training, endurance training, or concurrent training (> 4 weeks duration); comparison: control group; outcome: pre- and post-levels of hormones and cytokines; and study design: randomized and non-randomized controlled trials. We used a random-effect model for the meta-analysis. The raw mean difference in hormones from baseline to post-intervention was presented alongside 95% confidence intervals (CI). Further, the certainty of evidence quality and the risk of bias were assessed. RESULTS: A total of 3689 records were identified, of which 14 studies were eligible for inclusion. Most studies examined adolescents with fewer studies on children (age < 12 years, N = 5 studies) and females (N = 2 studies). Nine exercise training programs used endurance training, five studies used resistance training, and no eligible study used concurrent training. The meta-analysis showed no significant effect of exercise training on testosterone (MD = 0.84 nmol/L), cortisol (MD = - 17.4 nmol/L), or SHBG (MD = - 5.58 nmol/L). Subgroup analysis showed that resistance training significantly increased testosterone levels after training (MD = 3.42 nmol/L) which was not observed after endurance training (MD = - 0.01 nmol/L). No other outcome differed between training types. Exercise training resulted in small and non-significant changes in GH (MD = 0.48 ng/mL, p = 0.06) and IGF-I (MD = - 22.90 ng/mL, p = 0.07). GH response to endurance training may be age-dependent and evident in adolescents (MD = 0.59 ng/mL, p = 0.04) but not when children and adolescents are pooled (MD = 0.48 ng/mL, p = 0.06). Limited evidence exists to conclude on IL-6 and TNF-α effects of exercise training. Assessments of GRADE domains (risk of bias, consistency, directness, or precision of the findings) revealed serious weaknesses with most of the included outcomes (hormones and cytokines). CONCLUSIONS: This systematic review suggests that exercise training has small effects on hormonal concentrations in children and adolescents. Changes in testosterone concentrations with training are evident after resistance training but not endurance training. GH's response to training may be affected by maturation and evident in adolescents but not children. Further high-quality, robust training studies on the effect of resistance training, endurance training, and concurrent training are warranted to compare their training-specific effects. REGISTRATION: PROSPERO: CRD42021241130.

Fully covered self-expandable metal stent placed over a stapled colon anastomosis in an animal model: A pilot study of colon metabolism over the stent.

Background and Aim: Anastomotic leakage (AL) in colorectal resection and primary anastomosis is a common and feared complication. Fully covered self-expandable metal stents (FCSEMSs) have been used for the treatment of AL. It is still unknown whether FCSEMSs affect anastomosis healing negatively by causing ischemia. In an animal study, we investigated the metabolic effects over a FCSEMS covering a stapled colon anastomosis. Methods: Seven pigs were investigated using microdialysis after laparotomy, colon resection, and anastomosis with stent placement. Measurements were done at the proximal and distal ends of the anastomosis and at a reference catheter placed at the small intestine. Measurements of glucose, pyruvate, lactate, glycerol, and the lactate/pyruvate ratio (L/P) were carried out. Results: Lactate and L/P were significantly higher at the oral part of the anastomosis, while glucose showed a small declining tendency. At the distal part of the anastomosis, glucose decreased significantly after the resection but did not reach zero. Lactate increased significantly whereas L/P increased only slightly. Glycerol levels were stable. Conclusion: Colon resection caused initially hypermetabolism in the intestinal ends next to the resection site. This hypermetabolism neither deteriorated nor turned into ischemia during the initial postoperative course, but the start of hypoxemia could not be excluded during the study and after the placement of an FCSEMS.

Oxygen Uptake in Repeated Cycling Sprints Against Different Loads Is Comparable Between Men and Preadolescent Boys.

Children recover faster than adults in repeated sprints, but it is unclear if their aerobic responses differ. Purpose: This study tested the hypothesis that aerobic response (VO2) during repeated sprints is greater in preadolescent boys than in men. Further, this study compared normalization with conventional ratio-scaling and scaling with the use of body mass (BM) as a covariate. Methods: Nine boys (age: 11.8 ± 0.6 years, swimmers) and 11 men (age: 21.7 ± 0.6 years, recreational athletes) performed 10 maximal 6-s cycling sprints separated by 24-s of passive recovery, against two loads (optimum and 50% of optimum). Oxygen uptake (VO2) was measured continuously. Results: Men's mean power output (MPO) was greater than boys in each sprint, both in absolute (unscaled) values ( p < 0.05) and when adjusted for lean leg volume ( p < 0.05). Children had lower absolute VO2 ( p < 0.05) than men, but when it was adjusted for BM or power-output, VO2 was comparable between men and boys. Thus, most of the difference in VO2 between men and boys was due to body size and power-output differences. Conclusion: Our results suggest that men and boys have similar VO2 during repeated sprints when appropriately adjusted to body mass or power output. Results highlight the importance of using appropriate scaling methods to compare adults' and children's aerobic responses to high-intensity exercise.

Effects of Core Strength Training on Skiing Economy in Elite Junior Cross-Country Skiers.

Purpose: In cross-country (XC) skiing, the ability to use an efficient technique is essential for performance. The study aimed to compare the effects of supplemental static or dynamic core strength training on skiing economy in elite junior XC skiers. Methods: Twenty-four elite junior XC skiers (14 women, 10 men; 17.8 ± 1.1 years; 67.8 ± 10.0 kg, 173.7 ± 6.4 cm) participated in this study. Participants were allocated either to a static core training (ST) group (n =12) or to a dynamic core training (DT) group (n = 12). Both groups continued their normal aerobic endurance and muscular strength training. Experimental groups performed a 15 minutes, 3 days/week core strength-training program for 9 weeks and in addition to their training. Submaximal and maximal roller ski testing was conducted before and after the 9-week training period. Results: Results showed no significant interaction between groups for energetic costs in any of the submaximal workloads (first, p = .33; second, p =.79; third, p = .25). Pooled data showed a significant improvement in energetic cost pre- to posttesting in the first and third workload (ES 0.40, p = .0006 and ES 0.42, p = .04 respectively). Nine weeks of static or dynamic core strength training in elite junior XC skiers had a small effect on energetic cost in submaximal roller skiing. Conclusion: The type of supplemental core strength training does not seem to affect economy in submaximal roller skiing.

Results of postoperative microdialysis intraperitoneal and at the anastomosis in patients developing anastomotic leakage after rectal cancer surgery.

Introduction: Anastomotic leakage postoperatively in patients operated with rectum resection and primary anastomosis is a common and feared complication. We have studied seven patients with an anastomotic leakage after surgery and compared them with 13 patients without complications.Methods: Metabolic measurements with microdialysis were done during the first seven postoperative days, with measurements of glucose, pyruvate, lactate and glycerol. The lactate/pyruvate ratio was calculated. Measurements were performed subcutaneously, intraperitoneally and at the anastomosis. The inflammatory cytokines, IL 6 and IL 10, were measured intravenously and intraperitoneally 48 hours postoperatively.Results: Intravenous and intraperitoneal IL 6 were higher in the leakage group. Around the small intestine (intraperitoneally), we found that patients developing anastomotic leakage had higher lactate and lactate/pyruvate ratio immediately after surgery. They also showed lower glycerol levels. At the anastomosis, we found higher lactate and lactate/pyruvate ratio in anastomotic leak patients after the fourth postoperative day.Conclusions: The results indicate that a possible mechanism behind an anastomotic leakage is an impaired circulation and thus insufficient saturation to the small intestine peroperatively. This develops into an inflammation both intraperitoneally and intravenously, which, if not reversed, spread within the gastrointestinal tract .The colorectal anastomosis is the most vulnerable part of the gastrointestinal tract postoperatively and hypoxia and inflammation may occur there, and an anastomosis leakage will be the consequence.

Part 2: Forensic attribution profiling of Russian VX in food using liquid chromatography-mass spectrometry.

This work is part two of a three-part series in this issue of a Sweden-United States collaborative effort towards the understanding of the chemical attribution signatures of Russian VX (VR) in synthesized samples and complex food matrices. In this study, we describe the sourcing of VR present in food based on chemical analysis of attribution signatures by liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with multivariate data analysis. Analytical data was acquired from seven different foods spiked with VR batches that were synthesized via six different routes in two separate laboratories. The synthesis products were spiked at a lethal dose into seven food matrices: water, orange juice, apple purée, baby food, pea purée, liquid eggs and hot dog. After acetonitrile sample extraction, the samples were analyzed by LC-MS/MS operated in MRM mode. A multivariate statistical calibration model was built on the chemical attribution profiles from 118 VR spiked food samples. Using the model, an external test-set of the six synthesis routes employed for VR production was correctly identified with no observable major impact of the food matrices to the classification. The overall performance of the statistical models was found to be exceptional (94%) for the test set samples retrospectively classified to their synthesis routes.

Source attribution profiling of five species of Amanita mushrooms from four European countries by high resolution liquid chromatography-mass spectrometry combined with multivariate statistical analysis and DNA-barcoding.

Source attribution profiling of five species of Amanita mushrooms from four European countries was performed using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) combined with multivariate statistical analysis. Initially, species determination was carried out morphologically and was verified by DNA-analysis. This data was then combined with chemical profiling, generated from LC-HRMS full scan analysis. The untargeted data was processed and the 720 most abundant peaks in the LC-HRMS chromatogram were used to build a multivariate PLS-DA model. The two independent methods for species determination showed 100% correlation, indicating the potential use of chemical profiling as a supporting technique to genetic methods. When specimens of one species were studied, significant variation related to the region of growth was found. The potential of the geo-positioning was shown for A. phalloides from Sweden, Denmark and UK and A. virosa from Sweden and Denmark. Additionally, A. virosa specimens could be attributed to three geographically different regions of Sweden.

Analysis of paralytic shellfish toxins, potential chemical threat agents, in food using hydrophilic interaction liquid chromatography-mass spectrometry.

A novel method for determining paralytic shellfish toxin (PST) profiles in food was developed using a combination of silica and strong cation exchange (SCX) solid phase extraction (SPE) coupled to hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). Besides the risk for natural contamination of seafood and drinking water, PSTs also pose potent threats through intentional contamination of food, due to their high toxicity and the wide distributions of toxin-producing algae. The new preparation method aim to maintain the samples' original toxin profiles by avoiding conditions known to induce interconversion or degradation of the PSTs. The method was evaluated for PST extraction from water, milk, orange juice, apple purée, baby food, and blue mussels (Mytilus edulis). The extracts were found to produce reproducible retention times in HILIC-MS/MS analysis. When an authentic toxic mussel sample was analyzed using the novel method, saxitoxin and gonyautoxin-3 were identified, in agreement with data acquired using the Lawrence pre-column oxidation high-performance liquid chromatography-fluorescence detection (HPLC-FLD) method. Overall recoveries of the PSTs from tested foods by the novel method ranged from 36% to 111%.

Stochastic anomaly detection in eye-tracking data for quantification of motor symptoms in Parkinson's disease.

Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson's disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patients with Parkinson's disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects tracking visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson's disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson's disease.

Analysis of the mushroom nephrotoxin orellanine and its glucosides.

Orellanine is a nephrotoxin found in various Cortinaceae mushroom species. Unintentional consumption after these species were confused with edible mushrooms such as Cantharellus tubaeformis has caused several casualties. In this work, a quantitative HPLC-ESI-MS/MS method for total orellanine in Cortinarius rubellus, spiked blood plasma, and a mushroom stew prepared from C. tubaeformis with the addition of a single specimen of C. rubellus is presented. The existence of mono- and diglucosylated orellanine in C. rubellus was also proven, although quantitative analysis could not be obtained for the glucosides due to rapid hydrolyzation to orellanine in the extract. Extraction with 3 M HCl or water mainly yielded orellanine, while MeOH or acidified MeOH mainly extracted mono- and diglucosylated orellanine. The highest recovery of total orellanine was obtained with 3 M HCl, which was subsequently used for quantitative analysis. A C18 HPLC column and low pH in the eluents retained all these toxins. Orellanine could be detected at a 4.9 ng/mL level in all extracts, which is well below the threshold for acute toxic effects. Additionally, the fragmentation pattern of orellanine upon electrospray MS/MS was probed. The method described is useful for two important applications. First, it allows quantitative analysis of processed food products that may be contaminated by orellanine from Cortinaceae mushrooms. Second, orellanine is currently being evaluated as a potential cure of metastatic renal cancer, and this work provides a method for monitoring orellanine at low concentrations within the therapeutic interval in blood serum.

A concept study on identification and attribution profiling of chemical threat agents using liquid chromatography-mass spectrometry applied to Amanita toxins in food.

Accidental or deliberate poisoning of food is of great national and international concern. Detecting and identifying potentially toxic agents in food is challenging due to their large chemical diversity and the complexity range of food matrices. A methodology is presented whereby toxic agents are identified and further characterized using a two-step approach. First, generic screening is performed by LC/MS/MS to detect toxins based on a list of selected potential chemical threat agents (CTAs). After identifying the CTAs, a second LC/MS analysis is performed applying accurate mass determination and the generation of an attribution profile. To demonstrate the potential of the methodology, toxins from the mushrooms Amanita phalloides and Amanita virosa were analyzed. These mushrooms are known to produce cyclic peptide toxins, which can be grouped into amatoxins, phallotoxins and virotoxins, where α-amanitin and ß-amanitin are regarded as the most potent. To represent a typical complex food sample, mushroom stews containing either A. phalloides or A. virosa were prepared. By combining the screening method with accurate mass analysis, the attribution profile for the identified toxins and related components in each stew was established and used to identify the mushroom species in question. In addition, the analytical data was consistent with the fact that the A. virosa specimens used in this study were of European origin. This adds an important piece of information that enables geographic attribution and strengthens the attribution profile.

Evaluation of a generic multi-analyte method for detection of >100 representative compounds correlated to emergency events in 19 food types by ultrahigh-pressure liquid chromatography-tandem mass spectrometry.

A generic extraction procedure combined with triple quadrupole mass spectrometric detection was evaluated for multi-residue analysis in 19 different foods. Measurable peaks could be obtained at relevant concentrations for 108 out of a total of 127 targeted compounds representing a wide range of physicochemical properties and compound classes related to emergency situations. Recoveries were determined for all 19 foods spiked with the 108 compounds. Seventy-five percent of the compounds had extraction recoveries of 70% or higher, with no compound below 46%. Suppression or enhancement effects on the MS response of the compounds dissolved in the extracts were low, as more than 80% of them had matrix effects between -35% and +20% and no compound was below -44% compared to matrix-free standard. In a validation, all compounds could be quantified at 200 µg/kg and 400 µg/kg food sample and 81% of the compounds at 40 µg/kg. It is concluded that the method is useful for the detection of various types of organic chemical toxicants at levels generally well below concentration thresholds for severe acute intoxication.

Optimization of the in vitro cardiac safety of hydroxamate-based histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors have shown promise in treating various forms of cancer. However, many HDAC inhibitors from diverse structural classes have been associated with QT prolongation in humans. Inhibition of the human ether a-go-go related gene (hERG) channel has been associated with QT prolongation and fatal arrhythmias. To determine if the observed cardiac effects of HDAC inhibitors in humans is due to hERG blockade, a highly potent HDAC inhibitor devoid of hERG activity was required. Starting with dacinostat (LAQ824), a highly potent HDAC inhibitor, we explored the SAR to determine the pharmacophores required for HDAC and hERG inhibition. We disclose here the results of these efforts where a high degree of pharmacophore homology between these two targets was discovered. This similarity prevented traditional strategies for mitigating hERG binding/modulation from being successful and novel approaches for reducing hERG inhibition were required. Using a hERG homology model, two compounds, 11r and 25i, were discovered to be highly efficacious with weak affinity for the hERG and other ion channels.