The Beneficial Effects of Nordic Walking Training Combined with Time-Restricted Eating 14/24 in Women with Abnormal Body Composition Depend on the Application Period.

The aim of the study was to assess the impact of two lengths of Nordic walking (NW) training interventions combined with time-restricted eating (TRE) on improving body-composition parameters, lipid profiles, and levels of selected adipokines in women with elevated body mass. Overweight and obese women (n = 55, age: 21-85) were recruited. Four groups were selected: 6 weeks (SG6, n = 13) and 12 weeks intervention (SG12, n = 13); and two control groups: CON6 (n = 13) and CON12 (n = 13). The training sessions took place three times a week (60 min each) and were conducted outdoors under the supervision of a professional coach. The training intensity was determined individually. The extended NW program combined with TRE induced a significant weight reduction in SG12 by 1.96 kg (p = 0.010) and fat tissue by 1.64 kg (p = 0.05). The proposed interventions did not affect LBM, TBW [kg], VFA, and lipid profile. The LDL/HDL ratio changed with a small size effect. The leptin concentration differed between groups (p = 0.006), but not over time. For resistin, the differentiating factor was time (p = 0.019), with lower results observed after the intervention. The change in leptin concentration was negatively correlated with its baseline concentration (p = 0.025). Extended to 12 weeks, this intervention allows for an improvement in body composition. Neither 6 nor 12 weeks of training and fasting affected the lipoprotein profile. It is, therefore, indicated to recommend prolonged training protocols and to inform patients that beneficial effects will be seen only after prolonged use of training and time-restricted eating.

The Impact of a 6-Week Nordic Walking Training Cycle and a 14-Hour Intermittent Fasting on Disease Activity Markers and Serum Levels of Wnt Pathway-Associated Proteins in Patients with Multiple Myeloma.

Background: Multiple myeloma (MM) accounts for about 10-15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Materials and methods: Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60 min workouts 3 times a week was conducted. Body mass and composition as well as the levels of vitamin D, calcium and phosphorus, beta2-microglobulin, and albumin were examined before and after the completion of the training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN), and Tartrate-resistant acid phosphatase 5b (TRACP 5b). Results: There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumins was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p = 0.001 and p = 0.022, respectively). The change in the concentration of this vitamin negatively correlated with the concentration of TRACP 5b (r = -0.413, p = 0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p = 0.026, time vs. group: p = 0.033) and TRACP 5b (time: p < 0.001, time vs. group p < 0.001) was indicated. Conclusions: The obtained results allow one to indicate the training with the poles as a safe and beneficial form of physical activity that should be recommended to patients suffering from MM. However, the results obtained in the present study are not sufficient to show the beneficial effect of IF applied without trainings.

Fibroblast Growth Factor Receptor Inhibitors Decrease Proliferation of Melanoma Cell Lines and Their Activity Is Modulated by Vitamin D.

Regardless of the unprecedented progress in malignant melanoma treatment strategies and clinical outcomes of patients during the last twelve years, this skin cancer remains the most lethal one. We have previously documented that vitamin D and its low-calcaemic analogues enhance the anticancer activity of drugs including a classic chemotherapeutic-dacarbazine-and an antiangiogenic VEGFRs inhibitor-cediranib. In this study, we explored the response of A375 and RPMI7951 melanoma lines to CPL304110 (CPL110), a novel selective inhibitor of fibroblast growth factor receptors (FGFRs), and compared its efficacy with that of AZD4547, the first-generation FGFRs selective inhibitor. We also tested whether 1,25(OH)2D3, the active form of vitamin D, modulates the response of the cells to these drugs. CPL304110 efficiently decreased the viability of melanoma cells in both A375 and RPMI7951 cell lines, with the IC50 value below 1 µM. However, the metastatic RPMI7951 melanoma cells were less sensitive to the tested drug than A375 cells, isolated from primary tumour site. Both tested FGFR inhibitors triggered G0/G1 cell cycle arrest in A375 melanoma cells and increased apoptotic/necrotic SubG1 fraction in RPMI7951 melanoma cells. 1,25(OH)2D3 modulated the efficacy of CPL304110, by decreasing the IC50 value by more than 4-fold in A375 cell line, but not in RPMI7951 cells. Further analysis revealed that both inhibitors impact vitamin D signalling to some extent, and this effect is cell line-specific. On the other hand, 1,25(OH)2D3, have an impact on the expression of FGFR receptors and phosphorylation (FGFR-Tyr653/654). Interestingly, 1,25(OH)2D3 and CPL304110 co-treatment resulted in activation of the ERK1/2 pathway in A375 cells. Our results strongly suggested possible crosstalk between vitamin D-activated pathways and activity of FGFR inhibitors, which should be considered in further clinical studies.

Wheat Bread Enriched with House Cricket Powder (Acheta domesticus L.) as an Alternative Protein Source.

The house cricket (Acheta domesticus L.) is one of four edible insect species introduced to the EU market as a novel food and alternative protein source. Innovative products, such as cricket flour, are increasingly appearing on supermarket shelves and can offer an alternative to traditional cereals, while providing the body with many valuable nutrients of comparable quality to those found in meat and fish. The aim of this study was to investigate the possibility of using cricket powder as a substitute for wheat flour in the production of bread. The physicochemical properties of cricket powder were evaluated in comparison to wheat flour. As a result of technological studies, bread compositions with 5%, 10% and 15% replacements of wheat flour by cricket powder were designed and their quality characteristics (physicochemical, sensory and microbiological) were evaluated. Cricket powder was characterised by a higher protein (63% vs. 13.5%) and fat (16.3% vs. 1.16%) content and a lower carbohydrate (9.8% vs. 66%) and fibre (7.8% vs. 9.5%) content as compared to wheat flour. The tested preparations had a similar pH (6.9 and 6.8, respectively, for cricket powder and flour) and fat absorption capacity (0.14 vs. 0.27 g oil/g powder, respectively, for cricket powder and flour) but different water holding capacities and completely different colour parameters. All breads had good microbiological quality after baking and during 7 days of storage. In instrumental tests, the 10 and 15% replacements of wheat flour by cricket powder affected the darker colour of the breads and caused a significant increase in the hardness of the breads. The research has shown that the optimal level of replacement, which does not significantly affect the physiochemical and sensory characteristics, is 5% cricket powder in the bread recipe. Considering the results obtained and the fact that insects provide a sufficient supply of energy and protein in the human diet, are a source of fibre, vitamins and micronutrients, and have a high content of monounsaturated and polyunsaturated fatty acids, the suitability of cricket powder for protein enrichment of bakery products is confirmed.

Effect of Various Hydration Strategies on Work Intensity and Selected Physiological Indices in Young Male Athletes during Prolonged Physical Exercise at High Ambient Temperatures.

Background: In high temperatures, adequate hydration is vital for sustained physical exercise. This study explores the effect of three hydration strategies on physiological indices and work intensity. Methods: The research involved 12 healthy males who engaged in three test series, each separated by a one-week interval. During the trials, participants underwent a 120 min cycling session in a thermal climate chamber (temperature: 31 ± 2 °C, humidity: 60 ± 3%, air movement: <1 m/s). Measurements of rectal temperature (Tre) and heart rate (HR), and assessment of subjective workload perception, and thermal comfort were made both before and during the exercise. The computation of the physical strain index (PSI) relied on Tre and HR values. Three hydration strategies (isotonic drink, water, and no hydration) were administered before, during, and after the exercise. Results: Regardless of the hydration strategy, the participants' mean body mass decreased as a result of the exercise. Statistically significant differences in HR were observed between the no-hydration and water groups (p < 0.036). The mean PSI values significantly varied between hydration strategies, with the no hydration group exhibiting a higher PSI compared to the isotonic drink or water groups (p < 0.001). Conclusions: All hydration strategies contribute to thermoregulatory processes and mitigate the rise in internal body temperature during sustained physical exercise in elevated ambient temperatures.

Rheological properties of blood in multiple myeloma patients.

Multiple myeloma (MM) is considered to be one of the hematological malignancies formed by excessive and abnormal proliferation of plasmocytes. Among other parameters, several blood tests are used to diagnose multiple myeloma. The hemorheological profile in multiple myeloma is not widely studied. Hemorheology includes the study of measuring the deformability and aggregation of erythrocytes, blood viscosity, and sedimentation rate. The degree of deformability of blood cells is necessary to maintain proper vital functions. Proper deformability of red blood cells ensures proper blood circulation, tissue oxidation and carbon dioxide uptake. The aim of the study was to compare morphology and blood rheology parameters in patients with MM and healthy individuals. The study included 33 patients with MM, and 33 healthy subjects of the same age. The hematological blood parameters were evaluated using ABX MICROS 60 hematology analyzer. The LORCA Analyzer to study erythrocyte aggregation and deformability. Patients with MM had lower red blood cells count (RBC) (9.11%) (p < 0.001) and half time of total aggregation (T1/2) (94.29%) (p < 0.001) values and higher mean corpuscular volume (MCV) (5.50%) (p < 0.001), aggregation index (AI) (68.60%) (p < 0.001), total extent of aggregation (AMP) (87.92%) (p < 0.001) values than the healthy control group. Aggregation in patients with MM is different compared to healthy individuals. It was observed that the percentage of cell aggregation is almost 50% higher than in the control group. The study of morphology, aggregation and deformability of erythrocytes in patients with suspected MM may be helpful in making clinical decisions.

The Impact of Intermittent Hypoxic Training on Aerobic Capacity and Biometric-Structural Indicators among Obese Women-A Pilot Study.

BACKGROUND: Obesity, a common lifestyle-related condition, is correlated with factors like inadequate physical activity. Its connection to diverse health issues presents a significant challenge to healthcare. This pilot study investigated the effects of hypoxic training on aerobic capacity and biometric-structural indicators in obese women. The secondary objective was to determine the feasibility, effectiveness, and safety of the planned research procedures and their potential for larger-scale implementation. MATERIAL AND METHODS: Forty-one non-trained women with first-degree obesity were randomly assigned to even normobaric hypoxic training (H + E), normoxic training (E), passive exposure to hypoxia (H), and a control group (C). Training sessions were conducted three times a week for four weeks (12 training sessions). Body composition parameters were assessed, metabolic thresholds were determined, and maximal oxygen consumption (VO2max) was measured before and after interventions. RESULTS: The results demonstrated that training in hypoxic conditions significantly affected somatic parameters, with the H + E group achieving the best outcomes in terms of weight reduction and improvements in body composition indicators (p < 0.001). Normoxic training also induced a positive impact on body weight and body composition, although the results were less significant compared to the H + E group (p < 0.001). Additionally, training in hypoxic conditions significantly improved the aerobic capacity among the participants (p < 0.001). The H + E group achieved the best results in enhancing respiratory endurance and oxygen consumption (p < 0.001). CONCLUSIONS: The results of this pilot study suggest, that hypoxic training can be effective for weight reduction and improving the aerobic capacity in obese women. Despite study limitations, these findings indicate that hypoxic training could be an innovative approach to address obesity and related conditions. Caution is advised in interpreting the results, considering both the strengths and limitations of the pilot study. Before proceeding to a larger-scale study, the main study should be expanded, including aspects such as dietary control, monitoring physical activity, and biochemical blood analysis.

IP-10 for the Diagnosis and Treatment Monitoring of Tuberculosis in Children.

PURPOSE: To determine the utility of interferon-gamma-inducible protein 10 (IP-10) for identifying active tuberculosis (TB) and TB infection (TBI) in children in BCG-vaccinated populations, establish its diagnostic performance characteristics, and evaluate changes in IP-10 level during anti-TB chemotherapy. METHODS: Concentrations of IP-10 and IFN-γ were measured in QuantiFERON-TB Gold (QFT) supernatants in children with suspected TB or due to recent TB contact. A total of 225 children were investigated: 33 with active TB, 48 with TBI, 83 TB contacts, 20 with suspected TB but other final diagnoses, and 41 controls. In 60 children, cytokine responses were evaluated at a follow-up visit after 2 months of anti-TB treatment. RESULTS: IP-10 expression was significantly higher in infected children (active TB and TBI cases) than in uninfected individuals. IP-10 proved effective in identifying TB infection at its optimal cut-off (>1084.5 pg/mL) but was incapable of differentiating between children with active TB and TBI. Combining IP-10 and IFN-γ increased the QFT sensitivity. IP-10 but not IFN-γ decreased significantly during anti-TB treatment in children with active TB (p = 0.003). CONCLUSION: IP-10 identifies TB infection and declines during anti-TB chemotherapy in children. Incorporating IP-10 into new immunodiagnostic assays could improve TB diagnosis and allow for treatment monitoring.

Resting metabolic rate is increased after a series of whole body vibration in young men.

Resting metabolic rate (RMR) is the largest component of total energy expenditure and increasing it can be of great importance in reducing excess body fatness. Whole body vibration (WBV) can affect energy expenditure during single session of WBV, but the effects of repeated WBV on resting metabolic rate have not been reported. The purpose of this study was to investigate whether a series of WBV would increase resting metabolism in young men. Thirty-two healthy men aged of 21-23 were recruited and randomly assigned to two 16-member groups: a group participating in the WBV intervention and a group without the intervention. The intervention lasted 2 weeks and WBV was performed 5 times a week. Diet, physical activity, body composition and resting metabolic rate were analyzed in the participants. In WBV group significantly increased resting oxygen uptake (p = 0.049) and consequently RMR (p = 0.035) after the intervention. Similar changes were not observed in the control group. This indicates that applied type of vibration in this study can be an addition to obesity therapy, in which, WBV can, among other beneficial metabolic effects, increase RMR and thus total energy expenditure.

The Effect of a Six-Week Nordic Walking Training Cycle on Oxidative Damage of Macromolecules and Iron Metabolism in Older Patients with Multiple Myeloma in Remission-Randomized Clinical Trial.

Multiple myeloma (MM) is an incurable hematologic malignancy originating from clonal plasma cell proliferation within the bone marrow, predominantly affecting older individuals. While anemia serves as a diagnostic criterion for MM, it often ameliorates upon achieving disease remission. Iron metabolism parameters have emerged as potential prognostic indicators in MM. Notably, physical exercise has been established to influence iron metabolism. This study aimed to assess alterations in serum iron, ferritin, and transferrin concentrations, as well as leukocyte gene expression, in MM patients undergoing a six-week cycle of Nordic walking training. Thirty patients divided into an exercise group (NW, n = 15, mean age 63.1 ± 8.4 years) and a control group (CG, n = 15, mean age: 63.5 ± 3.6 years) completed the study protocol. Blood samples were collected at baseline, after three and six weeks of training, and after nine weeks. Serum ferritin, transferrin, and iron concentrations were measured, along with the leukocyte expression of genes. Additionally, serum oxidative damage marker levels were determined. Following the Nordic walking training cycle, a declining trend in serum ferritin concentrations was observed. Intracellular mRNA levels of genes associated with iron metabolism were positively influenced by the training regimen, indicating the potential impact of this physical activity on gene expression and ferritin concentrations. Although positive trends were noted, extended training periods might be requisite for significant changes. To conclude, moderate-intensity exercise induces favorable shifts in the analyzed parameters among MM patients, potentially influencing disease progression. Consequently, Nordic walking training is a safe recommendation for MM patients, though sustained training beyond six weeks could be necessary for notable effects on iron metabolism factors.

PDIA3 modulates genomic response to 1,25-dihydroxyvitamin D3 in squamous cell carcinoma of the skin.

An active form of vitamin D3 (1,25-dihydroxyvitamin D3) acts through vitamin D receptor (VDR) initiating genomic response, but several studies described also non-genomic actions of 1,25-dihydroxyvitamin D3, implying the role of PDIA3 in the process. PDIA3 is a membrane-associated disulfide isomerase involved in disulfide bond formation, protein folding, and remodeling. Here, we used a transcriptome-based approach to identify changes in expression profiles in PDIA3-deficient squamous cell carcinoma line A431 after 1,25-dihydroxyvitamin D3 treatment. PDIA3 knockout led to changes in the expression of more than 2000 genes and modulated proliferation, cell cycle, and mobility of cells; suggesting an important regulatory role of PDIA3. PDIA3-deficient cells showed increased sensitivity to 1,25-dihydroxyvitamin D3, which led to decrease migration. 1,25-dihydroxyvitamin D3 treatment altered also genes expression profile of A431ΔPDIA3 in comparison to A431WT cells, indicating the existence of PDIA3-dependent genes. Interestingly, classic targets of VDR, including CAMP (Cathelicidin Antimicrobial Peptide), TRPV6 (Transient Receptor Potential Cation Channel Subfamily V Member 6), were regulated differently by 1,25-dihydroxyvitamin D3, in A431ΔPDIA3. Deletion of PDIA3 impaired 1,25-dihydroxyvitamin D3-response of genes, such as PTGS2, MMP12, and FOCAD, which were identified as PDIA3-dependent. Additionally, response to 1,25-dihydroxyvitamin D3 in cancerous A431 cells differed from immortalized HaCaT keratinocytes, used as non-cancerous control. Finally, silencing of PDIA3 and 1,25-dihydroxyvitamin D3, at least partially reverse the expression of cancer-related genes in A431 cells, thus targeting PDIA3 and use of 1,25-dihydroxyvitamin D3 could be considered in a prevention and therapy of the skin cancer. Taken together, PDIA3 has a strong impact on gene expression and physiology, including genomic response to 1,25-dihydroxyvitamin D3.

Effects of Vibrotherapy with Different Characteristics and Body Position on Post-Exercise Recovery after Anaerobic Exercise.

The aim of this project was to indicate the optimal parameters such as frequency, duration of a single vibrotherapy, and body position, which will be used as a form of recovery modality after physical exercise. Sixteen healthy male volunteers were involved in this study. The aerobic and anaerobic capacity of participants was assessed. Each of the subjects performed a set of intensive physical exercises and then underwent vibrotherapy treatment. In random order, each of the men tested the effectiveness of eight of the combinations of frequency, duration, and body position. The effect of the procedure accelerating recovery was assessed 24 h after physical exercise with the Wingate test. Changes in oxygen saturation and biochemical markers (interleukins: Il-1ß, Il-6, and creatine kinase: CK), hemoglobin (Hb), and hematocrit (Hct) were assessed 1 h and 24 h after the physical effort. Lactate concentrations were measured 3, 15, 30, and 60 min after the end of the vibration. It was indicated that the optimal treatment should be based on lower ranges of frequency values (2-52 Hz). The procedure with raised feet is also more beneficial than the flat, supine position. To improve the overall work, and a number of biochemical markers (CK and Il-1ß), a 45 min treatment will be more efficient, because significantly lower CK activity was indicated for the 45 min treatment. For this duration, higher values of Il-1ß were indicated in the measurement carried out for samples collected 60 min after the treatment and lower in the measurement carried out 24 h after the treatment.

Mirogabalin Decreases Pain-like Behaviors by Inhibiting the Microglial/Macrophage Activation, p38MAPK Signaling, and Pronociceptive CCL2 and CCL5 Release in a Mouse Model of Neuropathic Pain.

Neuropathic pain is a chronic condition that significantly reduces the quality of life of many patients as a result of ineffective pain relief therapy. For that reason, looking for new analgesics remains an important issue. Mirogabalin is a new gabapentinoid that is a specific ligand for the α2σ-1 and α2σ-2 subunits of voltage-gated calcium channels. In the present study, we compared the analgesic effect of pregabalin and mirogabalin in a neuropathic pain chronic constriction injury (CCI) of the sciatic nerve in a mouse model. The main purpose of our study was to determine the effectiveness of mirogabalin administered both once and repeatedly and to explain how the drug influences highly activated cells at the spinal cord level in neuropathy. We also sought to understand whether mirogabalin modulates the selected intracellular pathways (p38MAPK, ERK, JNK) and chemokines (CCL2, CCL5) important for nociceptive transmission, which is crucial information from a clinical perspective. First, our study provides evidence that a single mirogabalin administration diminishes tactile hypersensitivity more effectively than pregabalin. Second, research shows that several indirect mechanisms may be responsible for the beneficial analgesic effect of mirogabalin. This study reports that repeated intraperitoneally (i.p.) mirogabalin administration strongly prevents spinal microglia/macrophage activation evoked by nerve injury, slightly suppresses astroglia and neutrophil infiltration, and reduces the p38MAPK levels associated with neuropathic pain, as measured on Day 7. Moreover, mirogabalin strongly diminished the levels of the pronociceptive chemokines CCL2 and CCL5. Our results indicate that mirogabalin may represent a new strategy for the effective pharmacotherapy of neuropathic pain.

Ductus venosus opens in high-risk pregnancies without signs of increased central venous pressure.

OBJECTIVES: It has been belived that changes in diastolic blood velocities in the fetal ductus venosus were due to increased central venous pressure secondary to increased fetal heart strain during hypoxia or heart failure. There have been recent reports of changes in ductus venosus blood velocity without signs of increased fetal heart strain. The aim of this evaluation was to compare blood velocity in the right hepatic vein as a marker of increased central venous pressure in relationship to changes in ductus venosus blood velocity. MATERIAL AND METHODS: Fifty pregnancies suspected of fetal growth resitriction were evaluated by Doppler ultrasound. Blood velocity was recorded in the right hepatic vein, ducus venosus and in the umbilical vein. Placental blood flow was also recorded in the uterine and umbilical arteries as well as the fetal middle cerebral artery. RESULTS: Increased umbilical artery pulsatility index was recorded in 19 fetuses and 20 has signes of brain sparing according to recordings in the middle cerebral artery. Abnormal blood velocity in the ductus venosus was recorded in 5 fetuses, none of these fetuses had an abnormal pulsatility in the right hepatic vein. CONCLUSIONS: Opening of the ductus venosus is not only related to fetal cardiac strain. This might indicate that the ductus venosus does not primarily open due to increased central venous pressure in moderate fetal hypoxia. Increased fetal cardiac strain might be a late event in the process of chronic fetal hypoxia.

The Role of Increased Expression of Sirtuin 6 in the Prevention of Premature Aging Pathomechanisms.

Sirtuins, in mammals, are a group of seven enzymes (SIRT1-SIRT7) involved in the post-translational modification of proteins-they are considered longevity proteins. SIRT6, classified as class IV, is located on the cell nucleus; however, its action is also connected with other regions, e.g., mitochondria and cytoplasm. It affects many molecular pathways involved in aging: telomere maintenance, DNA repair, inflammatory processes or glycolysis. A literature search for keywords or phrases was carried out in PubMed and further searches were carried out on the ClinicalTrials.gov website. The role of SIRT6 in both premature and chronological aging has been pointed out. SIRT6 is involved in the regulation of homeostasis-an increase in the protein's activity has been noted in calorie-restriction diets and with significant weight loss, among others. Expression of this protein is also elevated in people who regularly exercise. SIRT6 has been shown to have different effects on inflammation, depending on the cells involved. The protein is considered a factor in phenotypic attachment and the migratory responses of macrophages, thus accelerating the process of wound healing. Furthermore, exogenous substances will affect the expression level of SIRT6: resveratrol, sirtinol, flavonoids, cyanidin, quercetin and others. This study discusses the importance of the role of SIRT6 in aging, metabolic activity, inflammation, the wound healing process and physical activity.

Vitamin D Modulates the Response of Patient-Derived Metastatic Melanoma Cells to Anticancer Drugs.

Melanoma is considered a lethal and treatment-resistant skin cancer with a high risk of recurrence, making it a major clinical challenge. Our earlier studies documented that 1,25(OH)2D3 and its low-calcaemic analogues potentiate the effectiveness of dacarbazine and cediranib, a pan-VEGFR inhibitor. In the current study, a set of patient-derived melanoma cultures was established and characterised as a preclinical model of human melanoma. Thus, patient-derived cells were preconditioned with 1,25(OH)2D3 and treated with cediranib or vemurafenib, a BRAF inhibitor, depending on the BRAF mutation status of the patients enrolled in the study. 1,25(OH)2D3 preconditioning exacerbated the inhibition of patient-derived melanoma cell growth and motility in comparison to monotherapy with cediranib. A significant decrease in mitochondrial respiration parameters, such as non-mitochondrial oxygen consumption, basal respiration and ATP-linked respiration, was observed. It seems that 1,25(OH)2D3 preconditioning enhanced cediranib efficacy via the modulation of mitochondrial bioenergetics. Additionally, 1,25(OH)2D3 also decreased the viability and mobility of the BRAF+ patient-derived cells treated with vemurafenib. Interestingly, regardless of the strict selection, cancer-derived fibroblasts (CAFs) became the major fraction of cultured cells over time, suggesting that melanoma growth is dependent on CAFs. In conclusion, the results of our study strongly emphasise that the active form of vitamin D, 1,25(OH)2D3, might be considered as an adjuvant agent in the treatment of malignant melanoma.

Lung Ultrasound in the Evaluation of Lung Disease Severity in Children with Clinically Stable Cystic Fibrosis: A Prospective Cross-Sectional Study.

With the increasing longevity of cystic fibrosis (CF), there is a growing need to minimise exposure to ionising radiation in patients who undergo regular imaging tests while monitoring the course of the lung disease. This study aimed to define the role of lung ultrasounds (LUS) in the evaluation of lung disease severity in children with clinically stable CF. LUS was performed on 131 patients aged 5 weeks to 18 years (study group) and in 32 healthy children of an equivalent age range (control group). Additionally, an interobserver study was performed on 38 patients from the study group. In CF patients, the following ultrasound signs were identified: I-lines; Z-lines; single, numerous and confluent B-lines; Am-lines; small and major consolidations; pleural line abnormalities and small amounts of pleural fluid. The obtained results were evaluated against an original ultrasound score. LUS results were correlated with the results of chest X-ray (CXR) [very high], pulmonary function tests (PFTs) [high] and microbiological status [significant]. The interobserver study showed very good agreement between investigators. We conclude that LUS is a useful test in the evaluation of CF lung disease severity compared to routinely used methods. With appropriate standardisation, LUS is highly reproducible.

Effect of Whole-Body Vibration Training on Hemorheological Blood Indices in Young, Healthy Women.

The aim of the study is to assess the effect of single and 12-week WBVT and training without vibration on changes in hemorheological blood indices and plasma fibrinogen levels in young, healthy women. Three groups are distinguished: the experimental group-participating in WBVT (n = 17); the comparison group-implementing the same physical exercise protocol without the vibration factor (n = 12); and the control group-no intervention (n = 17). In the experimental and comparison group, blood is collected before and after the first and last training, while in the control group, blood is collected twice, 3 months apart. After a series of WBVT, a significant decrease in the mean erythrocyte volume and mean hemoglobin mass in erythrocytes, as well as a slight increase in the mean erythrocyte hemoglobin concentration, is found, and the effect of the last training is a significant decrease in plasma volume. Under the influence of repeated WBVT, there is an increase in erythrocyte deformability at low shear stress and an increase in the aggregation amplitude. The study shows that WBVT improves blood flow in the vessels and does not affect erythrocyte aggregation and the level of fibrinogen, which confirms the safety of this form of exercise.

Effect of Whole-Body Vibration on Serum Levels of Brain Derived Neurotrophic Factor and Cortisol in Young, Healthy Women.

Vibration exercises on a platform (whole-body vibration, WBV), widely used in rehabilitation, sports medicine, and fitness, is an alternative to strength effort. The presented study assessed the effect of a 12-week cycle of vibration training on the serum concentrations of brain-derived neurotrophic factor (BDNF) and cortisol in young women (trial ID: ACTRN 12621000114842). Volunteers were assigned to three groups: performing exercises on a vibrating platform (n = 17), performing identical exercises without a platform (n = 12), and passive control group (n = 17). The concentration of BDNF and cortisol was assessed four times: before the first training session, 5 min after it, also before, and 5 min after the last training session. There were no statistically significant changes in the groups or among groups for both substances. WBV in the presented form did not increase the secretion of BDNF and is not a stressful stimulus.

Effects of Elevated Body Temperature on Selected Physiological Indices and Thermal Stress in Athletes and Non-Athletes.

The purpose of this study was to determine the effects of active and passive overheating. A group of athletes (A) and non-athletic men (N) underwent an exercise stress test at elevated ambient temperature and sauna bathing until an increase in rectal temperature of 1.2°C was observed. It was shown that group A performed physical exercise for a longer period of time, which elicited significantly higher amounts of work performed in the stress test. Both forms of overheating caused a significant decrease in BM and a significant change in plasma volume, while greater dehydration was observed after active overheating. Changes observed in group A were higher than in group N. MCV levels were initially higher in group A. The levels in both groups decreased after sauna bathing, although in non-athletes the decrease was greater. Both forms of overheating increased Hb, HCT, and SBP, while only the non-athletic group showed a decrease in DBP after the exercise stress test. However, a decrease in DBP was observed in both groups after sauna bathing. The PSI increased after both tests, yet to a higher extent after the stress test than after sauna bathing. The PSI was negatively correlated with VO2max in both groups. The increase in cortisol concentration was higher after sauna bathing. There was a correlation between cortisol levels and the work performed during the stress test in group A. Endurance training resulted in more efficient thermoregulatory mechanisms in athletes.