Treatment Outcomes of Adolescents Compared to Younger Pediatric Patients with Acute Myeloid Leukemia: Do They Need a Special Approach?

BACKGROUND: The reports of studies that compare the survival of adolescents and young adults with younger children with acute myeloid leukemia (AML) are contradictory. PATIENTS AND METHODS: We retrospectively analyzed 220 AML patients aged 0-18 years treated in pediatric oncologic centers in Poland from 2015 to 2022. The evaluated group included 31 infants (below 1 year), 91 younger children (1-9.9 years), 59 older children (10-14.9 years), and 39 adolescents (15-18 years). RESULTS: A 5-year overall survival for adolescents was not significantly inferior compared to younger and older children (74.3 ± 7.6% vs. 80.5 ± 4.4% vs. 77.9 ± 5.1, p = 0.243). However, relapse-free survival was lower in adolescents compared to younger children (76.5 ± 7.8% vs. 65.7 ± 9.0%, p = 0.049), and treatment-related mortality tended to be higher (10.3% vs. 4.4%, p = 0.569). In the univariate analysis, high-risk genetics [HR, 2.0 (95% CI 1.1-3.6; p = 0.014)] and a leukocyte count at diagnosis above 100,000/µL [HR, 2.4 (95% CI 1.3-4.6; p = 0.004)] were found to be unfavorable prognostic factors for survival. CONCLUSIONS: Although we have not found that age over 15 years is an unfavorable factor for overall survival, the optimal approach to therapy in adolescents, as in other age groups, is to adjust the intensity of therapy to individual genetic risk and introduce targeted therapies when indicated.

Characteristics and Outcome of FLT3-ITD-Positive Pediatric Acute Myeloid Leukemia-Experience of Polish Pediatric Leukemia and Lymphoma Study Group from 2005 to 2022.

BACKGROUND: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10-15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the outcome and characteristics of FLT3-ITD-positive pediatric AML. METHODS: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations). RESULTS: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71, p = 0.041; 0.36 vs. 0.59, p = 0.0004; 0.47 vs. 0.70, p = 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27, p = 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33, p = 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27, p = 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69, p = 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44, p = 0.036). CONCLUSIONS: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.

Pediatric Acute Myeloid Leukemia Post Cytotoxic Therapy-Retrospective Analysis of the Patients Treated in Poland from 2005 to 2022.

Acute P./myeloid leukemia post cytotoxic therapy (AML-pCT) is rare complication of cancer treatment in childhood. The objective of the study was to identify clinical characteristics and provide an analysis of the outcomes in pediatric AML-pCT. We retrospectively analyzed the data of 40 children with AML-pCT, treated from 2005 to 2020 within the Polish Pediatric Leukemia and Lymphoma Study Group. The most common primary malignancies were acute lymphoblastic leukemia (32.5%) and brain tumors (20%). The median latency period was 2.9 years (range: 0.7-12.9). Probabilities of overall (OS), event-free (EFS), and relapse-free survival (RFS) in the whole cohort were 0.49 ± 0.08, 0.43 ± 0.08, and 0.64 ± 0.10, respectively. Significant improvements in outcomes were observed in patients treated from 2015-2022 (two induction cycles followed by stem cell transplantation-SCT in 69% of patients) compared to 2005-2014 (four induction cycles followed by SCT in 49% of patients). The probability of EFS increased from 0.30 ± 0.10 to 0.67 ± 0.12 (p = 0.07) and RFS increased from 0.46 ± 0.11 to 1.0 (p = 0.01). The poorest outcome (OS and EFS 0.25 ± 0.20) was in AML post brain tumor, mainly due to deaths from toxicities. To conclude, treatment results achieved in patients with AML-pCT treated from 2015-2022, with two induction cycles followed by immediate SCT, were better than those reported by other authors, and comparable to the results in de novo AML.

Colorectal Cancer-The Worst Enemy Is the One We Do Not Know.

BACKGROUND: Colorectal cancer is one of the most common cancers in humans. It is the third most frequently diagnosed malignant neoplasm and is the second highest cause of cancer mortality in the world. Every year, more and more people die of colorectal cancer because the diagnosis is conducted too late. This shows how important a role screening tests and the awareness of the population about the symptoms play in this aspect. This article aimed to determine the knowledge of the Polish population about morbidity, symptoms, prevention, and subjective feelings about the level of availability of knowledge about colorectal cancer. METHODS: In 2020, a study was conducted using an online questionnaire assessing the awareness of the Polish population about colorectal cancer. A self-authored questionnaire including questions about socio-demographic characteristics, and 18 questions related to substantive issues, was used. A research group was selected (n = 633). The substantive part of the questionnaire included questions examining the respondents' knowledge about morbidity, symptoms, prevention, and subjective feelings about the level of availability of knowledge about colorectal cancer. RESULTS: The respondents' awareness level was influenced by demographic factors, such as gender: (p < 0.05) and age (p < 0.05) and social factors, such as: level of education (p < 0.05) or professional situation (p < 0.05). Compared to thematic articles from other countries, the research group was divided into smaller subgroups due to the abovementioned factors, due to which it was possible to stratify and analyze the significance of differences between them.

Perspectives of Motor Functional Upper Extremity Recovery with the Use of Immersive Virtual Reality in Stroke Patients.

Stroke is one of the leading causes of disability, including loss of hand manipulative skills. It constitutes a major limitation in independence and the ability to perform everyday tasks. Among the numerous accessible physiotherapeutic methods, it is becoming more common to apply Virtual Reality "VR". The aim of this study was to establish whether immersive VR was worth considering as a form of physical therapy and the advisability of applying it in restoring post-stroke hand function impairment. A proprietary application Virtual Mirror Hand 1.0 was used in the research and its effectiveness in therapy was compared to classical mirror therapy. A total of 20 survivors after ischaemic stroke with comparable functional status were divided into a study group (n = 10) and control group (n = 10). Diagnostic tools included 36-Item Short Form Survey "SF-36" and the Fugl-Meyer Assessment Upper Extremity "FMA-UE". Collected metrics showed a normal distribution and the differences in mean values were tested by the student's t-test. In both, the study and control groups' changes were recorded. A statistically significant outcome for FMA-UE and SF-36 measured by the student's t-test for dependent or independent samples (p > 0.05) were obtained in both groups. Importantly, proven by conducted studies, an advantage of VR proprietary application was subjective sensations amelioration in pain and sensory impressions. Applying Virtual Mirror Hand 1.0 treatment to patients after a stroke appears to be a good solution and definitely provides the opportunity to consider VR applications as an integral part of the neurorehabilitation process. These results give a basis to plan further larger-scale observation attempts. Moreover, the development of the Virtual Mirror Hand 1.0 as an innovative application in physiotherapy may become equivalent to classical mirror therapy in improving the quality and effectiveness of the treatment used for post-stroke patients.

Multiple pathways mediate chloroplast singlet oxygen stress signaling.

KEY MESSAGE: Chloroplast singlet oxygen initiates multiple pathways to control chloroplast degradation, cell death, and nuclear gene expression. Chloroplasts can respond to stress and changes in the environment by producing reactive oxygen species (ROS). Aside from being cytotoxic, ROS also have signaling capabilities. For example, the ROS singlet oxygen (1O2) can initiate nuclear gene expression, chloroplast degradation, and cell death. To unveil the signaling mechanisms involved, researchers have used several 1O2-producing Arabidopsis thaliana mutants as genetic model systems, including plastid ferrochelatase two (fc2), fluorescent in blue light (flu), chlorina 1 (ch1), and accelerated cell death 2 (acd2). Here, we compare these 1O2-producing mutants to elucidate if they utilize one or more signaling pathways to control cell death and nuclear gene expression. Using publicly available transcriptomic data, we demonstrate fc2, flu, and ch1 share a core response to 1O2 accumulation, but maintain unique responses, potentially tailored to respond to their specific stresses. Subsequently, we used a genetic approach to determine if these mutants share 1O2 signaling pathways by testing the ability of genetic suppressors of one 1O2 producing mutant to suppress signaling in a different 1O2 producing mutant. Our genetic analyses revealed at least two different chloroplast 1O2 signaling pathways control cellular degradation: one specific to the flu mutant and one shared by fc2, ch1, and acd2 mutants, but with life-stage-specific (seedling vs. adult) features. Overall, this work reveals chloroplast stress signaling involving 1O2 is complex and may allow cells to finely tune their physiology to environmental inputs.

Gemtuzumab ozogamicin for relapsed or primary refractory acute myeloid leukemia in children-the Polish Pediatric Leukemia and Lymphoma Study Group experience.

Background: Gemtuzumab ozogamicin (GO), one of the first targeted drugs used in oncology, consists of an anti-cluster of differentiation 33 (CD33) monoclonal antibody bound to a derivative of cytotoxic calicheamicin. After the drug withdrawn in 2010 due to a significantly higher rate of early deaths, GO regained approval in 2017 for the treatment of newly diagnosed, refractory, or relapsed acute myeloid leukemia (AML) in adults and children over 15 years of age. The objective of the study was a retrospective analysis of clinical characteristics, treatment outcomes, and GO toxicity profile in children with primary refractory or relapsed (R/R) AML treated in Poland from 2008 to 2022. Methods: Data were collected through the Polish Registry of Acute Myeloid Leukemia. From January 2008 to December 2022, 35 children with R/R AML were treated with GO in seven centers of the Polish Pediatric Leukemia and Lymphoma Study Group. Results: Most of the children (30 of 35) received only one GO cycle in combination with various chemotherapy cycles (IDA-FLA, DOXO-FLA, FLA, FLAG, and others). Eighteen children (51%) achieved complete remission (CR), 14 did not respond to treatment, and three progressed. GO therapy was followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 18 children in CR. The 5-year overall survival (OS) after GO therapy was 37.1% ± 8.7% for the total cohort. There was a trend toward a superior outcome in patients with strong expression of CD33 expression (over 50% positive cells) compared with that in patients with lower expression of CD33 (OS, 41.2% ± 11.9% versus 27.8% ± 13.2%; p = 0.5; 5-year event-free survival, 35.4% ± 11.6% versus 25.7% ± 12.3%; p = 0.5, respectively). Children under 15 years have better outcome (OS, 34.9% ± 10.4% versus 30% ± 14.5%, p = 0.3). The most common adverse events were bone marrow aplasia, fever of unknown origin, infections, and elevated liver enzyme elevation. Sinusoidal obstruction syndrome occurred in two children. Conclusions: The use of GO in severely pretreated children, including those under 15 years of age, with previous failure of AML treatment is a feasible and effective bridging therapy to allo-HSCT with an acceptable toxicity profile.

Efficacy of ruxolitinib in acute lymphoblastic leukemia: A systematic review.

Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk molecular subtype with a gene expression profile similar to Philadelphia-positive ALL, but not harboring the BCR-ABL1 gene fusion. We aimed to investigate the efficacy of target therapy with the Janus kinase inhibitor, ruxolitinib, in patients with Ph-like ALL and molecular signature of JAK-STAT signaling pathway. A systematic search of the literature was performed to identify reports concerning administration of ruxolitinib in Ph-like ALL patients. Additionally, Polish Pediatric ALL registries were searched for patients with Ph-like ALL treated with ruxolitinib. Extracted information included epidemiological background, somatic aberrations, treatment response, and patient outcome. After PubMed database search, twelve patients were identified, and one was identified in the Polish Pediatric ALL registry. In nine patients gene fusions affecting JAK2 (n = 7) and EPOR (n = 2) were detected. Surface overexpression of CRLF2 and IKZF1 deletions were observed in two and three patients, respectively. Induction failure occurred in all the patients. Therapy with ruxolitinib led to complete (n = 7) and partial (n = 2) remission, in three individuals no information was found. Based on the limited number of studies describing the efficacy of ruxolitinib as an additional compound administrated with standard ALL therapy, we conclude that this approach can be considered in patients with aberrations activating JAK-STAT pathway.

The core autophagy machinery is not required for chloroplast singlet oxygen-mediated cell death in the Arabidopsis thaliana plastid ferrochelatase two mutant.

BACKGROUND: Chloroplasts respond to stress and changes in the environment by producing reactive oxygen species (ROS) that have specific signaling abilities. The ROS singlet oxygen (1O2) is unique in that it can signal to initiate cellular degradation including the selective degradation of damaged chloroplasts. This chloroplast quality control pathway can be monitored in the Arabidopsis thaliana mutant plastid ferrochelatase two (fc2) that conditionally accumulates chloroplast 1O2 under diurnal light cycling conditions leading to rapid chloroplast degradation and eventual cell death. The cellular machinery involved in such degradation, however, remains unknown. Recently, it was demonstrated that whole damaged chloroplasts can be transported to the central vacuole via a process requiring autophagosomes and core components of the autophagy machinery. The relationship between this process, referred to as chlorophagy, and the degradation of 1O2-stressed chloroplasts and cells has remained unexplored. RESULTS: To further understand 1O2-induced cellular degradation and determine what role autophagy may play, the expression of autophagy-related genes was monitored in 1O2-stressed fc2 seedlings and found to be induced. Although autophagosomes were present in fc2 cells, they did not associate with chloroplasts during 1O2 stress. Mutations affecting the core autophagy machinery (atg5, atg7, and atg10) were unable to suppress 1O2-induced cell death or chloroplast protrusion into the central vacuole, suggesting autophagosome formation is dispensable for such 1O2-mediated cellular degradation. However, both atg5 and atg7 led to specific defects in chloroplast ultrastructure and photosynthetic efficiencies, suggesting core autophagy machinery is involved in protecting chloroplasts from photo-oxidative damage. Finally, genes predicted to be involved in microautophagy were shown to be induced in stressed fc2 seedlings, indicating a possible role for an alternate form of autophagy in the dismantling of 1O2-damaged chloroplasts. CONCLUSIONS: Our results support the hypothesis that 1O2-dependent cell death is independent from autophagosome formation, canonical autophagy, and chlorophagy. Furthermore, autophagosome-independent microautophagy may be involved in degrading 1O2-damaged chloroplasts. At the same time, canonical autophagy may still play a role in protecting chloroplasts from 1O2-induced photo-oxidative stress. Together, this suggests chloroplast function and degradation is a complex process utilizing multiple autophagy and degradation machineries, possibly depending on the type of stress or damage incurred.

Beneficial effects of whole-body cryotherapy on glucose homeostasis and amino acid profile are associated with a reduced myostatin serum concentration.

The study investigated the effect of single and chronic (10 sessions) whole-body cryotherapy (WBC; 3-min, - 110 °C) on amino acid (AA) profile, myostatin, fibroblast growth factor 21 (FGF21), and concentrations of brain-derived neurotrophic factor (BDNF), irisin and adiponectin in relation to glucose homeostasis. Thirty-five, healthy men were randomly split into experimental (young: 28 ± 7 years and middle-aged: 51 ± 3 years) and control groups. Blood samples were taken before and 1 h after the first and last (10th) WBC session. Baseline myostatin correlated significantly with visceral fat area, glucose, insulin, HOMA-IR and irisin (all p < 0.05). The single session of WBC induced temporary changes in AA profile, whereas chronic exposure lowered valine and asparagine concentrations (p < 0.01 and p = 0.01, respectively) compared to the baseline. The chronic WBC reduced fasting glucose (p = 0.04), FGF21 (- 35.8%, p = 0.06) and myostatin (-18.2%, p = 0.06). Still, the effects were age-dependent. The decrease of myostatin was more pronounced in middle-aged participants (p < 0.01). Concentrations of irisin and adiponectin increased in response to chronic WBC, while BDNF level remained unchanged. By improving the adipo-myokine profile, chronic WBC may reduce effectively the risk of the metabolic syndrome associated with hyperinsulinemia, increased levels of valine and asparagine, and muscle atrophy.

Habitually inactive physically - a proposed procedure of counteracting cognitive decline in women with diminished insulin sensitivity through a high-intensity circuit training program.

This study verified the impact of five weeks of high-intensity circuit training (HICT) on changes in concentration of exerkines in relation to cognitive functions. Sedentary women (n = 33; age=39±13 years) were randomly assigned into the HICT (n = 21) group or the control group (n = 12). The HICT group performed 15 training sessions; meanwhile, the control group performed the HICT twice, only at baseline and at the end of the experiment. Blood samples were collected before, 1 h and 24 h after the first and last HICT, to evaluate the concentration of exerkines: brain-derived neurotrophic factor (BDNF), irisin, fibroblast growth factor-21 (FGF-21), interleukin-6 (IL-6) and cathepsin B (CATB) using enzyme immunoassay method. Cognitive functions and quality of life were assessed using the Vienna Test System and the Short Form Health Survey. HICT induced improvement of cognitive function and quality of life, and these changes were accompanied by an increase of BDNF and shifts in CATB concentration. HICT program caused a decrease in FGF-21 concentration, which was modified by age and insulin sensitivity. The improvement of cognitive functions was more pronounced in females, who experienced a drop in FGF-21. In summary, HICT program, that can be performed during pandemic, enhanced cognitive functions and this response was related to changes in exerkines.

Immunological Response and Match Performance of Professional Tennis Players of Different Age Groups During a Competitive Season.

ABSTRACT: Kozlowska, M, Zurek, P, Rodziewicz, E, Góral, K, Zmijewski, P, Lipinska, P, Laskowski, R, Walentukiewicz, AK, Antosiewicz, J, and Ziemann, E. Immunological response and match performance of professional tennis players of different age groups during a competitive season. J Strength Cond Res 35(8): 2255-2262, 2021-We aimed to investigate the effect of physical workloads on immunological response, match performance, and iron metabolism in professional tennis players of different age groups throughout the tournament season and to determine the interdependence of vitamin D status and inflammation. Thirty-eight young, male tennis players with a top national ranking (1-25) participated in this study and were assigned to the following age groups: cadets (CG), juniors (JG), and seniors (SG). Blood samples were collected at the beginning, midpoint, and end of the tournament season to assess the proinflammatory cytokine (tumor necrosis factor-alpha [TNF-α]), anti-inflammatory myokines (interleukin [IL]-6 and IL-10), heat shock proteins (HSP70, HSP27), iron metabolism markers, and vitamin D concentrations. The total number of matches (won and lost) at the national and international events was recorded. The IL-6 and IL-10 concentrations significantly increased across all groups in the middle and end of the tournament season (effect large and very likely). The TNF-α concentration was elevated at the end of the season in CG and SG. The increase in TNF-α concentration corresponded with an increase in hepcidin concentration in these groups. The significant increase in HSP27 concentration was only noticed in SG with normal vitamin D concentrations. In JG and SG, a mild seasonal increase in vitamin D concentration was noted, but still it was insufficient. The immunological response was not affected by the number of tennis matches; however, the anti-inflammatory effect was regulated by higher concentrations of vitamin D. Unexpectedly, most tennis players had vitamin D deficiency. Iron status remained unchanged.

Generating and characterizing single- and multigene mutants of the Rubisco small subunit family in Arabidopsis.

The primary CO2-fixing enzyme Rubisco limits the productivity of plants. The small subunit of Rubisco (SSU) can influence overall Rubisco levels and catalytic efficiency, and is now receiving increasing attention as a potential engineering target to improve the performance of Rubisco. However, SSUs are encoded by a family of nuclear rbcS genes in plants, which makes them challenging to engineer and study. Here we have used CRISPR/Cas9 [clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9] and T-DNA insertion lines to generate a suite of single and multiple gene knockout mutants for the four members of the rbcS family in Arabidopsis, including two novel mutants 2b3b and 1a2b3b. 1a2b3b contained very low levels of Rubisco (~3% relative to the wild-type) and is the first example of a mutant with a homogenous Rubisco pool consisting of a single SSU isoform (1B). Growth under near-outdoor levels of light demonstrated Rubisco-limited growth phenotypes for several SSU mutants and the importance of the 1A and 3B isoforms. We also identified 1a1b as a likely lethal mutation, suggesting a key contributory role for the least expressed 1B isoform during early development. The successful use of CRISPR/Cas here suggests that this is a viable approach for exploring the functional roles of SSU isoforms in plants.

Short-Term Resistance Training Supported by Whole-Body Cryostimulation Induced a Decrease in Myostatin Concentration and an Increase in Isokinetic Muscle Strength.

The study aimed to determine whether combining cryostimulation with resistance training would effectively increase muscle strength, and if so, whether this adaptation would be related to changes in circulating levels of exerkines (i.e., mediators of systemic adaptation to exercise). Twenty-five students completed 12 sessions of resistance training, each followed by either cryostimulation (n = 15, 3 min exposure at -110 °C) or passive recovery (n = 10). Prior to and post this intervention, participants performed two eccentric cycling bouts (before and after training). At these points, serum concentrations of muscle damage marker (myoglobin), exerkines (interleukin 6 (IL-6), interleukin 15 (IL-15), irisin, brain-derived neurotrophic factor), hypertrophy-related factors (myostatin, insulin-like growth factor 1), and muscle strength were measured. The applied procedure reduced the physiological burden of the second eccentric cycling bout and myoglobin concentrations only in the group subject to cryostimulation. The same group also exhibited decreased levels of myostatin (from 4.7 ± 1.7 to 3.8 ± 1.8 ng·mL-1, p < 0.05). A significant and large interaction between the group × time was noted in IL-15 concentration (p = 0.01, ηp2=0.27). Training and cryostimulation induced a positive and likely significant improvement of isokinetic muscle strength. Altogether, obtained results support the claim that resistance training combined with cold exposure modified muscle strength through modulation of myostatin and IL-15 concentrations.

Iron Status in Elderly Women Impacts Myostatin, Adiponectin and Osteocalcin Levels Induced by Nordic Walking Training.

Impaired iron metabolism is associated with increased risk of many morbidities. Exercise was shown to have a beneficial role; however, the mechanism is not well understood. The purpose of this study was to assess the relationship between exerkines and iron metabolism in elderly women before and after 12 weeks of Nordic Walking (NW) training. Exerkines like myostatin, adiponectin, and osteocalcin have been shown to have several positive effects on metabolism. Thirty-six post-menopausal women (66 ± 5 years old, mean ± SD) were randomly assigned to a NW intervention group (n = 18; body mass, 68.8 ± 11.37 kg; fat, 23.43 ± 7.5 kg; free fat mass, 45.37 ± 5.92 kg) or a control group (n = 18; body mass, 68.34 ± 11.81 kg; fat, 23.61 ± 10.03 kg; free fat mass, 44.73 ± 3.9 kg). The training was performed three times a week for 12 weeks, with the intensity adjusted to 70% of the individual maximum ability. Before and one day after the 12-weeks intervention, performance indices were assessed using a senior fitness test. Blood samples (5 mL) were obtained from the participants between 7 and 8 AM, following an overnight fast, at baseline and one day immediately after the 12-week training program. A significant and large time ´ group interaction was observed for iron (NW: 98.6 ± 26.68 to 76.1 ± 15.31; CON: 100.6 ± 25.37 to 99.1 ± 27.2; p = 0.01; = 0.21), myostatin (NW: 4.42 ± 1.97 to 3.83 ± 1.52; CON: 4.11 ± 0.95 to 4.84 ± 1.19; p = 0.00; = 0.62), adiponectin (NW: 12.0 ± 9.46 to 14.6 ± 10.64; CON: 12.8 ± 8.99 to 11.9 ± 8.53; p = 0.00; = 0.58), and osteocalcin (NW: 38.9 ± 26.04 to 41.6 ± 25.09; CON: 37.1 ± 33.2 to 37.2 ± 32.29; p = 0.03; = 0.13). Furthermore, we have observed the correlations: basal ferritin levels were inversely correlated with changes in myostatin (r = -0.51, p = 0.05), change in adiponectin, and change in serum iron (r = -0.45, p = 0.05), basal iron, and osteocalcin after training (r = -0.55, p = 0.04). These findings indicate that iron modulates NW training-induced changes in exerkine levels.

Prognostic value of respiratory index in haemodynamically stable patients with acute pulmonary embolism: The Respiratory Index model study.

BACKGROUND: Current strategies for prognostic stratification in haemodynamically stable patients with acute pulmonary embolism require improvement. The aims of this study in haemodynamically stable patients with acute pulmonary embolism were (a) to evaluate the prognostic value of a novel respiratory index (oxygen saturation in air to respiratory rate ratio) and (b) to derive a risk model which includes the respiratory index and evaluate its value in predicting 30-day mortality. METHODS: Prospective cohorts of haemodynamically stable patients with acute pulmonary embolism were merged to a collaborative database that served to create two subsequent derivation and validation cohorts based on a temporal criterion. The study outcome was 30-day all-cause death. RESULTS: Thirty-day all-cause death occurred in 7.5% and in 6.9% of patients in the derivation and validation cohorts (each composed of 319 patients). In the derivation cohort, the respiratory index (odds ratio 0.66, 95% confidence interval 0.48-0.90) and simplified Pulmonary Embolism Severity Index (odds ratio 9.16, 95% confidence interval 1.22-68.89) were predictors of 30-day mortality. The cut-off value of the respiratory index ⩽3.8 was identified to best predict 30-day all-cause death (15.4% vs 5.0%, odds ratio 2.94, 95% confidence interval 1.22-7.11). The respiratory index ⩽3.8 was combined with the simplified Pulmonary Embolism Severity Index to create the Respiratory Index model that showed a good discriminatory power in the derivation (c-statistic 0.703, 95% confidence interval 0.60-0.80) and in the validation cohort (c-statistic 0.838, 95% confidence interval 0.768-0.907). CONCLUSION: In hemodynamically stable patients with acute pulmonary embolism, the respiratory index was an independent predictor of 30-day all-cause death. The Respiratory Index model which includes the simplified Pulmonary Embolism Severity Index and the respiratory index, provides a good risk stratification of haemodynamically stable patients with acute pulmonary embolism.

The beneficial effects of 15 units of high-intensity circuit training in women is modified by age, baseline insulin resistance and physical capacity.

AIM: To investigate the effect of a single and 15 units of high-intensity circuit training (HICT) programme on glucose metabolism, myokines' response and selected genes' expression in women. METHODS: Thirty-three, non-active women (mean age: 38 ±â€¯12) were split into a HICT (n = 20) or a control group (CON, n = 13). The training protocol included three circuits of nine exercises with own body weight as a workload performed 3 times a week for five weeks. The CON group performed HICT twice. Blood samples were taken before, 1 h and 24 h after the first and last unit to determine IGF-1, myostatin, irisin, decorin, HSP27, interleukin-15 concentrations using the ELISA immunoenzymatic method. To evaluate HSPB1, TNF-α and DCN mRNA, real-time PCR was used. Pre- and post-intervention, the oral glucose test and body composition assessment were completed. RESULTS: The following parameters tended to decrease after the 5-week HICT program: insulin and HOMA-IR Training diminished insulin/IGF-1 ratio (51% CI: -63% to -34%) and induced the drop of myostatin concentration but significantly only among middle-aged women and at baseline insulin resistance. CONCLUSION: Obtained data revealed that HICT improved an insulin sensitivity and diminished myostatin concentration among older, insulin-resistant women with lower baseline physical capacity.

Acute Postexercise Change in Circulating Irisin Is Related to More Favorable Lipid Profile in Pregnant Women Attending a Structured Exercise Program and to Less Favorable Lipid Profile in Controls: An Experimental Study with Two Groups.

INTRODUCTION: The blood irisin concentrations may be affected both by exercise and pregnancy. We aimed to determine acute responses in serum irisin after a single exercise session and relationships between exercise-induced changes in this hormone and lipid profile in pregnancy. MATERIAL AND METHODS: It was an experimental study in 20 Caucasian women in normal pregnancy (age 30 ± 3 years, 28 ± 6 weeks of gestation; mean ± SD). Participants were assigned to training (n = 8) and control groups (n = 12). Before the experiment, women from the training group attended a structured exercise program 3 times a week for 6 weeks. Blood samples were collected before and 30 minutes after a single bout of 60-minute moderate- to high-intensity exercise to determine serum levels of irisin, insulin, glucose concentration, and lipid profile. RESULTS: At baseline, we recorded slightly lower irisin levels in the training group compared to controls (12.2 ± 2.4 and 13.9 ± 3.3 ng · ml-1, respectively). Only in the training group all women presented increase in irisin levels after exercise (on average by 14%); and this change was statistically significant (p = 0.002). In the controls, we found positive significant relationships between postexercise irisin change and low-density lipoproteins (R = 0.594; p = 0.04) and total cholesterol (R = 0.734; p = 0.006). Surprisingly, in the training group, these relationships were also significant but inverse (R = -0.738 and p = 0.036; R = -0.833 and p = 0.01, respectively). CONCLUSIONS: Training and control pregnant women responded differently to a single exercise session, both in the postexercise change in irisin and its relationship to the blood lipids. Only in the training group we observed the postexercise increase in irisin, which was related to more favorable lipid profile. Systematic prenatal physical activity may optimize the postexercise irisin response and lipid metabolism regulated by this hormone. Therefore, exercise programs should be promoted in pregnant women and obstetric care providers.

Kidney Transplant Outcome Is Associated with Regulatory T Cell Population and Gene Expression Early after Transplantation.

Successful long-term kidney allograft survival with parallel reduction of complications resulting from prolonged immunosuppressive treatment is a goal in kidney transplantation. We studied the immune changes in cell phenotypes and gene expression induced by kidney transplantation. Our goal was to find a phenotypic and/or transcriptional pattern that might be considered prognostic for the kidney transplant outcome. The analysis was performed prospectively on 36 KTx recipients sampled during the first year and followed for five years after transplantation and on 40 long-term KTx recipients (7.9 ± 2.2 y. post-KTx). The research involved flow cytometry assessment of lymphocyte subpopulations (including Tregs and CD3+CD8+CD28- lymphocytes) and gene expression analysis of immune-related genes (CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGFB, and TNFA). The analysis of patterns observed over the first post-KTx year was confronted with control, pretransplant, and long-term transplant results. Treg counts at months one and three post-KTx correlated positively with the current and future allograft function. FOXP3 gene expression at month one post-KTx was also associated with long-term allograft function. The KTx-induced CD3+CD8+CD28- population correlated with GZMB and PRF1 expression and suggested their cytotoxic properties. The size of the Treg population and regulatory FOXP3 gene expression in the early period after transplantation are associated with kidney transplant outcome. The outlined predictive power of the Treg population needs to be investigated further to be confirmed as one of the immune monitoring strategies that may help achieve the best long-term kidney allograft outcomes.

A 2-Week Specific Volleyball Training Supported by the Whole Body Cryostimulation Protocol Induced an Increase of Growth Factors and Counteracted Deterioration of Physical Performance.

Potentially beneficial effects of cold therapies on training adaptation still remain unequivocal. We have, thus, decided to evaluate the effects of a 2-week volleyball training program supported by 10 sessions of whole body cryostimulation (WBC) on growth factors and physical performance. Twenty healthy college-aged men and women randomly assigned either to the cryostimulation group (CRY) or the control group (CON; executed passive rest). Both groups took part in the same 2-weeks training program. Additionally, the CRY group attended in 10 cryo-sessions (3 min, -110°C temperature, five times/week). Blood samples were collected at baseline, 1 h after the first cryo-session as well as before and 1 h after the last session of WBC to assess growth factors, myokines concentration and the amino acid profile. Motor abilities were tested before commencing the training program and 2 days after its completion. The applied intervention resulted in an increase of brain-derived neurotrophic factor and insulin-like growth factor 1 concentrations. The adjusted effect describing the difference between groups in response to applied procedures was for both growth factors large and very likely in the CRY, higher than in the CON group (113%; Coefficient Interval: 38-230%, 45%; Coefficient Interval: 17-79%, respectively). Physical performance dropped in both groups, yet in the CRY group, the magnitude of change was smaller. The fibroblast growth factor dropped significantly 1 h following the first cryo-session, yet irisin remained statistically unchanged. The similar tendency was maintained after the whole procedure, still the range of changes was smaller. In the CRY group, an elevated uptake of tryptophan and valine noted in response to the whole intervention, could have induced a significant decrease of fasting glucose concentration (the adjusted effect small and very likely -6%; Coefficient Interval: -10 to -2%). Overall, a 2-week volleyball training program supported by the whole body cryostimulation protocol resulted in an increase of growth factors and offset a decline of physical performance. Thus these procedure can be applied in professional sport during competition period, especially among those disciplines focusing on an explosive power and ability to concentrate.