Search

Context: Female football is becoming an increasingly popular women's team sports discipline around the world. The Women's Football Committee in the Polish Football Association has developed a long-term strategic plan to popularize the discipline across the country and enhance girls' participation. On one hand, it is postulated to increase the number of female footballers, and on the other hand, it is crucial to decrease the number of girls quitting football prematurely. Objective: To find the reasons for sports career termination among female football players. Design: Cross-sectional with retrospective information about reasons of career termination. Setting: Online questionnaire was filled out by online access. Participants: Ninety-three former female footballers. Main Outcome Measures: Factors leading to career termination. Methods: Participants completed the online questionnaire. The analysis was performed referring to 2 groups: "injury group"—in which the injury was the main reason for quitting football, and "other group"—in which the female player stopped playing football due to all other factors. Results: Thirty percent of former Polish female football players terminated their career due to a long-term treatment for an injury. Over 27% (27.7%) females had ended their careers because they were not able to reconcile sports with work/studying. Over 10% (10.8%) of former football players reported that becoming a wife and/or mother was the reason for career termination. Losing motivation and interest in the sport was reported by 9.2% (n = 6) of present study participants who decided to terminate the career due to noninjury reasons. Conclusions: The results clearly show that more effort is needed to support female football players, especially after an injury, so that they do not quit the sport voluntarily. [ABSTRACT FROM AUTHOR]

Backgrounds: Balance performance and postural priority are important components of motor skill development. No published reports have investigated the differences in static balance abilities and postural priority among professional soccer players according to field position.Research Question: We hypothesized that static balance as well as dynamic postural priority is influenced by playing position in professional soccer players.Methods: The study covered a group of 101 elite professional soccer players who were divided into six subgroups according to playing positions: goalkeepers (G) (n = 10), central defenders (CD) (n = 15), external defenders (ED) (n = 15), central midfielders (CM) (n = 23), external midfielders (EM) (n = 15) and forwards (F) (n = 23). All participants completed the Delos Postural System Test using the standard protocol. The tests were performed unilaterally on non-dominant (NL) and dominant leg (DL) under static conditions (with open and closed eyes) standing on a stable platform and under dynamic conditions on an unstable base.Results: In the static test with open eyes (ST OE) there were no statistically significant differences between the legs and positions. In the static test with closed eyes (ST CE), the differences are statistically significant only between positions. Players on the CM position have significantly higher differences than G. In the dynamic postural priority test (DPPT) there is a difference between positions and legs. In fact, the statistically higher differentiation refers to players in the CM position relative to ED, CD, EM and F. We noticed a significantly greater difference in the NL compared to the DL.Significance: Static balance performance and postural priority varied with playing position in elite soccer players. Midfield players have better postural priority than players in other positions. Professional soccer players present greater balance postural priority on the non-dominant leg. [ABSTRACT FROM AUTHOR]

Objective: To measure the sensitivity and specificity of differences cut-off values for isokinetic Hcon/Qcon ratio in order to improve the capacity to evaluate (retrospectively) the injury of hamstring muscles in professional soccer screened with knee isokinetic tests. Design: Retrospective study. Methods: Medical and biomechanical data of professional football players playing for the same team for at least one season between 2010 and 2016 were analysed. Hamstring strain injury cases and the reports generated via isokinetic testing were investigated. Isokinetic concentric(con) hamstring(H) and quadriceps(Q) absolute strength in addition with Hcon/Qcon ratio were examined for the injured versus uninjured limbs among injured players, and for the injured and non-injured players. 2 x 2 contingency table was used for comparing variables: predicted injured or predicted uninjured with actual injured or actual uninjured. Sensitivity, specificity, accuracy, positive and negative predictive values, and positive and negative likelihood ratio were calculated for three different cut-off values (0.47 vs. 0.6 vs. 0.658) to compare the discriminative power of an isokinetic test, whilst examining the key value of Hcon/Qcon ratio which may indicate the highest level of ability to predispose a player to injury. McNemar’s chi2 test with Yates’s correction was used to determine agreement between the tests. PQStat software was used for all statistical analysis, and an alpha level of p <0.05 was used for all statistical comparisons. Results: 340 isokinetic test reports on both limbs of 66 professional soccer players were analysed. Eleven players suffered hamstring injuries during the analysed period. None of these players sustained recurrence of hamstring injury. One player sustained hamstring strain injury on both legs, thus the total number of injuries was 12. Application of different cut-off values for Hcon/Qcon significantly affected the sensitivity and specificity of isokinetic test used as a tool for muscle injury detection. The use of 0.47 of Hcon/Qcon as a discriminate value resulted in significantly lower sensitivity when compared to 0.658 threshold (sensitivity of 16.7% vs. 91.7%, respectively; t = 6.125,p = 0.0133). Calculated values of specificity (when three different cut-off were applied) were also significantly different. Threshold of 0.6 of Hcon/Qcon resulted with significantly lower specificity compared to 0.47 value (specificity of 46.9% vs. 94.5%, respectively; t = 153.0,p<0.0001), and significantly higher specificity when compared to 0.658 (specificity of 46.9% vs. 24.1%, respectively; t = 229.0, p<0.0001). Conclusion: The use of different cut-off values for Hcon/Qcon significantly affected the sensitivity and specificity of isokinetic testing. The interpretation of usefulness of isokinetic test as a screening tool in a group of male professional football players to predict hamstring injury occurrence within the next 12 months might be therefore significantly biased due to the different threshold values of Hcon/Qcon. Using one “normative” value as a cut-off (e.g. 0.47 or 0.60, or 0.658) to quantify soccer players (or not) to the group with a higher risk of knee injury might result in biased outcomes due to the natural strength asymmetry that is observed within the group of soccer players. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare isokinetic strength performance profiles in elite soccer players across different field positions. A total of 111 elite international players of Polish Ekstraklasa (the top division in Poland) were examined during the 2010–2015 seasons. The players were classified into six positional roles: central defenders (CD), external defenders (ED), central midfielders (CM), external midfielders (EM), forwards (F), and goalkeepers (G). The concentric isokinetic strength (peak torque [PT] of quadriceps and hamstrings, H/Q ratios) was calculated for the dominant leg and the non-dominant leg at angular velocity of 1.05 rad ·s–1, whereas to assess isokinetic muscle endurance, the total work [TW] at angular velocity of 4.19 rad ·s–1, was taken into consideration. The results showed that isokinetic strength performance varies significantly among players in different playing positions. The analysis of PT for quadriceps (PT-Q) and hamstrings (PT-H) generally showed that the goalkeepers and central midfielders had lower strength levels compared to other playing positions. In the case of PT-H and hamstring/quadricep (H/Q) peak torque ratios, statistically significant differences were also noted for the legs, where mean values noted for the dominant leg were higher than for the non-dominant leg. For TW for quadriceps (TW-Q) and hamstrings (TW-H), statistically significant differences were noted only between playing positions. TW-Q values for goalkeepers were lower than for central defenders and external midfielders. TW-H values for goalkeepers were lower than for central midfielders, central defenders and external midfielders. This study showed that specific functional activity of players in individual positions on the field influences the varied profile of isokinetic strength performance. [ABSTRACT FROM AUTHOR]

We have previously found that ex vivo expanded human CD4CD25Treg cells suppress proliferation of lymphoma B-cell lines. Here we demonstrate that the immunomodulatory drug lenalidomide potentiates suppression of lymphoma B-cell proliferation by freshly isolated CD4CD25Tregs, as well as suppression by Tregs expanded polyclonally in the presence of rapamycin from CD4CD25T cells or CD4CD25CD127T cells. The regulation of lymphoma cell proliferation by Tregs pre-expanded with 'third-party' allogeneic MoDCs in the presence of rapamycin was also potentiated by lenalidomide. Lenalidomide contributed to the suppression exerted by Tregs despite concomitant downregulation of Treg proliferation. Lenalidomide did not reduce the suppression of conventional T cells by expanded Tregs. The exposure of polyclonally expanded Tregs to lenalidomide did not significantly alter their phenotype. There was no uniform pattern of lenalidomide effect on Treg-mediated regulation of lymphoma B cells freshly isolated from patients. Freshly isolated lymphoma cells activated with multimeric CD40L and IL-4 to support their survival in vitro varied in their sensitivity to lenalidomide, and the regulatory effect of Tregs on such lymphoma cells ranged from suppression to help in individual patients. Lenalidomide potentiated or attenuated Treg effects on the survival of freshly isolated lymphoma cells. A combination of lenalidomide treatment with adoptive transfer of CD4CD25Tregs or CD4CD25CD127Tregs expanded ex vivo could be used to suppress proliferation of residual lymphoma in select patients with lymphoma responsive to the regulation by Tregs and sensitive to lenalidomide. [ABSTRACT FROM AUTHOR]

Activated regulatory T cells (Tregs) suppress proliferation and differentiation of normal B cells. In our study, allogeneic polyclonal CD4 + CD25 + Tregs and CD4 + CD25 + CD127loTregs expandedin vitroin the presence of rapamycin and low dose IL-2 suppressed proliferation of 11 out of 12 established lymphoma B-cell lines. The effect of expanded CD4 + CD25 + Tregs on survival of freshly isolated lymphoma B cells maintained in culture with soluble multimeric CD40L and IL-4 was variable across lymphoma entities. The survival of freshly isolated follicular lymphoma cells usually decreased in cocultures with CD4 + CD25 + Tregs. Treg effect on chronic lymphocytic leukemia/small lymphocytic lymphoma cells ranged from suppression to help in individual patients. CD4 + CD25 + Tregs or CD4 + CD25 + CD127loTregs expandedex vivowith rapamycin could be used to suppress regrowth of residual lymphoma after autologous hematopoietic cell transplantation (HCT), and to counteract both graft-versus-host disease and lymphoma re-growth after allogeneic HCT in select patients with lymphoma susceptible to the regulation by Tregs. [ABSTRACT FROM AUTHOR]

The main objective(s) of the study: The aim of this study was to analyze: a) abnormalities in the length of lower limb muscles, b) the correctness of movement patterns, and c) the impact of functional limitations of muscles on the correctness of fundamental movement patterns in a group of female soccer players, in relation to their skill level. Materials and Methods: 21 female soccer players from Polish Ekstraklasa and 22 players from the 1st Division were tested for lower limb muscle length restrictions and level of fundamental movement skills (with the Fundamental Movement Screen™ test concept by Gray Cook). Chi-square test was used for categorical unrelated variables. Differences between groups in absolute point values were analyzed using the non-parametric Mann-Whitney U test. Statistical significance was set at p<0.05. Results: Statistically significant higher number of measurements indicating an abnormal length of rectus femoris was observed in the 1st Division group (p = 0.0433). In the group of Ekstraklasa the authors obtained a significantly higher number of abnormal hamstring test results (p = 0.0006). Ekstraklasa players scored higher in the rotational stability test of the trunk (p = 0.0008), whereas the 1st Division players scored higher in the following tests: deep squat (p = 0.0220), in-line lunge (p = 0.0042) and active straight leg raise (p = 0.0125). The results suggest that there are different functional reasons affecting point values obtained in the FMS™ tests in both analyzed groups. Conclusions: The differences in the flexibility of rectus femoris and hamstring muscle observed between female soccer players with different levels of training, may result from a long-term impact of soccer training on the muscle-tendon system and articular structures. Different causes of abnormalities in fundamental movement patterns in both analyzed groups suggest the need for tailoring prevention programs to the level of sport skills represented by the players. [ABSTRACT FROM AUTHOR]

Isometric strength testing using a digital dynamometer is reliable for muscle function evaluation. It allows us to objectify manual strength assessment measurement. We tested intra- and inter-observer reliability of a user-friendly efficient digital dynamometer—the Forcemeter—equipped with a computer program to monitor the measurements and to store the data. Abduction, forward flexion, and external and internal rotation of both shoulders were tested three times in 20 healthy volunteers with no record of shoulder trauma. Isometric contracture was recorded in newtons. The first and the third test were carried out by Examiner A (intra-rater reliability); the second test, by Examiner B (inter-rater reliability). Good reliability was shown for intra-class correlation coefficient (ICC) values which mean moderate to high correlations (r = 0.66–0.93) for both examiners. Moderate to high correlations (r = 0.72–0.91) were found for comparisons between the results obtained by Examiner A. [ABSTRACT FROM AUTHOR]

An editorial is presented on expecting manuscripts for using estimation methods instead of null hypothesis statistical tests. Topics include statistical inference being the process of making inferences about populations using data from samples; and availability of alternative methods of statistical inference and promotion of the methods in statistical, medical, and physiotherapy journals.

The aim of the study was to recognise what participant-, training- and post-injury-related factors are associated with an injury and re-injury occurrence in female pole dancers (PDs). 320 female PDs fulfilled a custom survey. 1050 injuries were reported by 276 PDs, 59% of injuries were related to lower extremity, 39% to upper extremity and 10% to spine and trunk. 156 PDs reported sustaining a re-injury, and overall, 628 re-injuries were reported. The median weekly pole-specific training session volume was 90 min and 240 min in the low and high qualified group, respectively. The total training volume was 180 min in the low qualified PDs and 240 min in the high qualified group. PDs with higher height and spending more time on pole-specific training in studio and on other forms of training have higher odds of sustaining an injury. PDs with lower level of experience in training, who sustained an injury, and who had a shorter pause between the moment of injury and the return to performance, and thus who did not fully recover, have higher odds of sustaining a re-injury. Sport-specific injury prevention strategies should be developed and implemented in this cohort, since over 85% of pole dancers reported sustaining some kind of injury. [ABSTRACT FROM AUTHOR]

• Stemness-related genes are upregulated in human colon cancer cells which survived 5-FU treatment. • Imatinib inhibits the regrowth of 5-FU-pretreated human colon cancer cells under normoxia and hypoxia. • A combination of imatinib and PRI-2191 downregulates stemness-related genes in 5-FU refractory cells more efficiently than imatinib alone. • PRI-1906 abolishes the effect of imatinib on gene expression in 5-FU-refractory HCT-116 cells undergoing renewal under normoxia. • Imatinib cooperates with PRI-2191 interfering with colorectal cancer renewal in vitro following treatment with 5-FU. Conventional cytotoxic drugs preferentially eliminate differentiated cancer cells but spare relatively more resistant stem-like cancer cells capable to initiate recurrence. Due to cancer cell plasticity, the stem-like phenotype can be also acquired by cancer cells refractory to treatment with cytotoxic drugs. We investigated whether drugs inhibiting receptor tyrosine kinases could be used to target human colon cancer cells initiating cancer regrowth following conventional cytotoxic treatment. The moderately differentiated cell line HT-29 and poorly differentiated cell line HCT-116 were exposed to 5-fluorouracil (5-FU). Cells that resisted the exposure to 5-FU were subsequently treated with imatinib or sunitinib. Both drugs reduced clonogenicity of 5-FU-refractory cells under normoxic and hypoxic culture conditions. The expression of numerous stemness-related genes was upregulated in cancer cells following the exposure to 5-FU, and remained at a high level in 5-FU-refractory cells undergoing renewal under normoxia, but decreased spontaneously under hypoxia. Imatinib downregulated the expression of stemness-related genes in cells undergoing renewal under normoxia. A combination of imatinib with PRI-2191, an analogue of 1,25-dihydroxyvitamin D 3 , downregulated stemness-related genes in HCT-116/5-FU cells more efficiently than imatinib alone. A synthetic analogue of 1,25-dihydroxyvitamin D 2 (PRI-1906) abolished the effect of imatinib on gene expression in HCT-116/5-FU cells undergoing renewal under normoxia. Sunitinib promoted shift of phenotype of HT-29/5-FU cells undergoing renewal toward stem-like one. It suggests that the phenotype shift toward stemness induced by sequential sunitinib treatment following 5-FU treatment could increase a risk of cancer recurrence. In contrast to sunitinib, imatinib could be used both to interfere with cancer regrowth after conventional chemotherapy and to downregulate the expression of stemness-related genes in residual colon cancer cells capable to initiate cancer recurrence. The findings suggest that imatinib could also be combined with vitamin D analogue PRI-2191 to prevent recurrence more efficiently than imatinib alone and to compensate for vitamin D deficiency resulting from imatinib treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to perform the translation and cross-cultural adaptation of the Achilles tendon Total Rupture Score (ATRS) into Polish version, and to evaluate its reliability and validity.Methods: The ATRS was translated into Polish language according to the Beaton recommendations. A total number of 71 patients previously treated surgically (from 2011 to 2015), due to the Achilles tendon rupture, were enrolled in this study. ATRS-Polish was performed twice within a period of 5-10 days. To evaluate test-retest reliability, intra-rater coefficient (ICC) was calculated. Construct validity was determined by the Spearman’s rank coefficient correlation between the ATRS-Polish and a Polish version of EQ-5D-5L questionnaire.Results: Test-retest reliability was found to be excellent (ICC 0.9). The mean and standard deviation of the first and second assessment amounted 87.4 ± 14.0 and 88.4 ± 13.2, respectively. Construct validity analysis showed a strong correlation between the ATRS and the EQ-5D-5L score (r = − 0.69.) and moderate correlation between ATRS and actual comfort (r = 0.47).Conclusions and perspectives: Polish version of the Achilles tendon Total Rupture Score was found to be reliable and valid.Level of evidence: Level II. [ABSTRACT FROM AUTHOR]

Purpose: Glenohumeral range of motion adaptations may affect throwing athletes and contribute to shoulder injury. The purpose of this study was to evaluate shoulder rotation deficits among elite professional handball players and its correlation to the presence of shoulder pain and morphological changes.Methods: Eighty-seven elite professional handball players and 41 healthy non-athlete volunteers participated in the study. Evaluations included measurement of range of internal and external rotation, total arch of motion, identification of shoulder pain and ultrasound scan for diagnosis of rotator cuff tears and internal impingement.Results: Glenohumeral rotational deficits (>20-25°) were found among 11 players group (13%). The throwing shoulders in the players group showed a decrease in internal rotation and an increase in external rotation with significantly larger ranges among players compared to the non-athlete group. Internal rotation deficit >20° was associated with higher incidence of shoulder pain among players. Both internal rotation deficits (>25°) and total arch of motion deficit (>20°) co-existed with higher incidence of internal impingement. Shoulder pain was common (36/97-41%) and was associated with decreased external rotation and total arch of motion. Internal impingement (found in 13/87-15%) correlated with decreased rotation ranges and a greater deficit in total arch of motion, whereas higher gain in external rotation correlated with a partial rotator cuff tear (found in 12/87-14%).Conclusions: Shoulder pathologies and problems commonly affected the group of handball players. Greater glenohumeral rotational deficits in throwing shoulders of handball players correlate with shoulder pain and internal impingement, while increased external rotation with partial rotator cuff tears. Such deficits affect 13% of the athlete population. Major clinical relevance of the study is to monitor handball players' shoulders both clinically and by proper imaging. Evaluation of range of rotation seems to identify shoulders at risk of the pathology.Level Of Evidence: Cross-Sectional study with control group, Level II. [ABSTRACT FROM AUTHOR]

A correction to the article "Statistical Inference Through Estimation: Recommendations From the International Society of Physiotherapy Journal Editors," by M. R. Elkins et al, that was published in a 2022 issue is presented.

This study aimed to evaluate the capacity of hypocalcemic analogues of 1α,25-dihydroxyvitamin D2 (1,25D2) and 1α,25-dihydroxyvitamin D3 (1,25D3) to inhibit regrowth and regulate the stemness-related gene expression in colon cancer cells undergoing renewal after exposure to 5-fluorouracil (5-FU). All of the tested analogues of 1,25D2 equally potently decreased the clonogenicity and the proliferative activity of HT-29 cells which survived the exposure to 5-FU, but differently regulated gene expression of these cells during their renewal. 1,25D2 and analogues (PRI-1907 and PRI-1917), as well as 1,25D3 and analogue PRI-2191, decreased the relative expression level of several stemness-related genes, such as NANOG, OCT3/4, PROM1, SOX2, ALDHA1, CXCR4, in HT-29/5-FU cells during their renewal, in comparison to untreated HT-29/5-FU cells. The other 1,25D2 analogues (PRI-1906 and PRI-1916) were not capable of downregulating the expression of these stemness-related genes as the analogues PRI-1907 and PRI-1917 did. All of the tested vitamin D analogues upregulated CDH1, the gene encoding E-cadherin associated with epithelial phenotype. Out of the series of analogues studied, side-chain branched analogues of 1,25D2 (PRI-1907, PRI-1917) and the analogue of 1,25D3 (PRI-2191) might be used to target cancer cells with stem-like phenotypes that survive conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Plantaris tendon, peronus brevis tendon and flexor hallucis longus tendon augmentation, commonly used in Achilles tendon rupture, often lead to weakening of injured foot and they require the immobilization after the surgery. It is essential to develop the technique, which gives no such limitation and allows for immediate functional improvement.Methods: We present our method of minimally invasive, endoscopic Achilles tendon reconstruction using semitendinosus and gracilis tendons with Endobutton stabilization.Results: Posterolateral and posteromedial portals were made approximately 3 cm above the posterosuperior part of the calcaneus to clean the area of the Achilles tendon endoscopically. Then the hamstrings are harvested and prepared for the "Endobutton" system. A midline incision of the skin is performed approximately 1 cm above the posterosuperior part of the calcaneus to approach to the posterosuperior part of the calcaneus. Then under fluoroscopy the calcaneus was drilled through using K-wire. The distal end of the graft equipped with an Endobutton loop was entered into the drilled tunnel in the calcaneus. Later, 8 consecutive skin incisions are performed. Proximal ends of the graft were brought out through the native Achilles tendon reaching medial and lateral skin incisions. The final step was to transfer and tie the graft ends through the most proximal skin incision.Conclusions: This minimally invasive, endoscopic technique allows reconstruction of the Achilles tendon using semitendinosus and gracilis tendons with Endobutton stabilization and can be used in so-called "difficult", resistant cases as a "salvage procedure". [ABSTRACT FROM AUTHOR]

Resistance to glucocorticosteroids (GCs) is a major adverse prognostic factor in B-ALL, but the molecular mechanisms leading to GC resistance are not completely understood. Herein, we sought to elucidate the molecular background of GC resistance in B-ALL and characterize the therapeutic potential of targeted intervention in these mechanisms. Using exploratory bioinformatic approaches, we found that resistant cells exhibited significantly higher expression of MEK/ERK (MAPK) pathway components. We found that GC-resistant ALL cell lines had markedly higher baseline activity of MEK and small-molecule MEK1/2 inhibitor selumetinib increased GCs-induced cell death. MEK inhibitor similarly increased in vitro dexamethasone activity in primary ALL blasts from 19 of 22 tested patients. To further confirm these observations, we overexpressed a constitutively active MEK mutant in GC-sensitive cells and found that forced MEK activity induced resistance to dexamethasone. Since recent studies highlight the role GC-induced autophagy upstream of apoptotic cell death, we assessed LC3 processing, MDC staining and GFP-LC3 relocalization in cells incubated with either DEX, SEL or combination of drugs. Unlike either drug alone, only their combination markedly increased these markers of autophagy. These changes were associated with decreased mTOR activity and blocked 4E-BP1 phosphorylation. In cells with silenced beclin-1 (BCN1), required for autophagosome formation, the synergy of DEX and SEL was markedly reduced. Taken together, we show that MEK inhibitor selumetinib enhances dexamethasone toxicity in GC-resistant B-ALL cells. The underlying mechanism of this interaction involves inhibition of mTOR signaling pathway and modulation of autophagy markers, likely reflecting induction of this process and required for cell death. Thus, our data demonstrate that modulation of MEK/ERK pathway is an attractive therapeutic strategy overcoming GC resistance in B-ALL patients. [ABSTRACT FROM AUTHOR]

Purpose: Prenyl ammonium iodides (Amino-Prenols, APs), semi-synthetic polyprenol derivatives were studied as prospective novel gene transfer agents. Methods: AP-7, -8, -11 and -15 (aminoprenols composed of 7, 8, 11 or 15 isoprene units, respectively) were examined for their capacity to form complexes with pDNA, for cytotoxicity and ability to transfect genes to cells. Results: All the carriers were able to complex DNA. The highest, comparable to commercial reagents, transfection efficiency was observed for AP-15. Simultaneously, AP-15 exhibited the lowest negative impact on cell viability and proliferation—considerably lower than that of commercial agents. AP-15/DOPE complexes were also efficient to introduce pDNA to cells, without much effect on cell viability. Transfection with AP-15/DOPE complexes influenced the expression of a very few among 44 tested genes involved in cellular lipid metabolism. Furthermore, complexes containing AP-15 and therapeutic plasmid, encoding the TIMP metallopeptidase inhibitor 2 (TIMP2), introduced the TIMP2 gene with high efficiency to B16-F10 melanoma cells but not to B16-F10 melanoma tumors in C57BL/6 mice, as confirmed by TIMP2 protein level determination. Conclusion: Obtained results indicate that APs have a potential as non-viral vectors for cell transfection. [ABSTRACT FROM AUTHOR]

Inhibition of spleen tyrosine kinase (SYK) in tonic B-cell receptor (BCR) signal-dependent diffuse large B-cell lymphomas (DLBCLs) inhibits cellular proliferation, decreases cholesterol biosynthesis, and triggers apoptosis, at least in part via a mechanism involving decreased activity of phosphatidylinositol 3-kinase/AKT axis. Because forkhead box O1 (FOXO1) is a major effector of this pathway, we investigated the role of FOXO1 in toxicity of BCR pathway inhibition. Inhibition of SYK in DLBCL cells with tonic BCR signaling decreased phospho-AKT and phospho-FOXO1 levels and triggered FOXO1-driven gene expression. Introduction of constitutively active FOXO1 mutant triggered cell cycle arrest and apoptosis, indicating that increased FOXO1 activity is toxic to these DLBCL cells. Depletion of FOXO1 with short hairpin RNA led to almost complete resistance to chemical SYK inhibitor R406, demonstrating that FOXO1 is also required for R406-induced cell death. FOXO1 in these cells is also involved in regulation of expression of the critical master regulator of cholesterol biosynthesis, SREBP1. Because HRK is the key effector of SYK inhibition, we characterized a mechanism linking FOXO1 activation and HRK induction that involves caspase-dependent cleavage of HRK's transcriptional repressor DREAM. Because AKT in lymphoma cells can be regulated by other signals than BCR, we assessed the combined effects of the AKT inhibitor MK-2206 with R406 and found markedly synergistic FOXO1-dependent toxicity. In primary DLBCLs, FOXO1 expression was present in 80% of tumors, correlated with SYK activity, and was associated with longer overall survival. These results demonstrate that FOXO1 is required for SYK and AKT inhibitor-induced toxicity. [ABSTRACT FROM AUTHOR]

HOXA genes encode transcription factors, which are crucial for embryogenesis and tissue differentiation and are involved in the early stages of hematopoiesis. Aberrations in HOXA genes and their cofactor MEIS1 are found in human neoplasms, including acute myeloid leukemia (AML). The present study investigated the role of HOXA4, HOXA5 and MEIS1 promoter DNA methylation and mRNA expression in AML. Samples from 78 AML patients and 12 normal bone marrow (BM) samples were included. The levels of promoter DNA methylation were determined using quantitative methylation-specific polymerase chain reaction (PCR; qMSP) and the relative expression levels were measured using reverse transcription quantitative PCR in Ficoll-separated BM mononuclear cells and in fluorescent activated cell sorting-sorted populations of normal hematopoietic progenitors. In total, 38.1 and 28.9% of the patients exhibited high methylation levels of HOXA4 and HOXA5, respectively, compared with the control samples, and MEIS1 methylation was almost absent. An inverse correlation between HOXA4 methylation and expression was identified in a group of patients with a normal karyotype (NK AML). An association between the genes was observed and correlation between the DNA methylation and expression levels of the HOXA gene promoter with the expression of MEIS1 was observed. Patients with favorable chromosomal aberrations revealed a low level of HOXA4 methylation and decreased expression levels of HOXA5 and MEIS1 compared with the NK AML and the adverse cytogenetic risk patients. The NK AML patients with NPM1 mutations exhibited elevated HOXA4 methylation and expression levels of HOXA5 and MEIS1 compared with the NPM1 wild-type patients. Comparison of the undifferentiated BM-derived hematopoietic CD34+CD38low, CD34+CD38+ and CD15+ cells revealed a gradual decrease in the expression levels of these three genes and an increase in HOXA4 promoter methylation. This differentiation-associated variability was not observed in AML, which was classified according to the French-American-British system. [ABSTRACT FROM AUTHOR]

Highlights: [•] Promoter regions of genes encoding CCAAT/enhancer binding proteins: alpha, delta and epsilon are hypermethylated in a large proportion of AML patients. [•] Promoter methylation levels of CEBPA and CEBPD are not observed in normal bone marrow nor hematopoietic precursor cells and are correlated with decreased gene expression. [•] AML cytogenetic risk groups and patients with particular translocation are characterized by distinct methylation/expression profile of CEBPs encoding genes. [Copyright &y& Elsevier]

Objective: The aim of the study was to: 1) evaluate the differences in pre-post operative knee functioning, mechanical stability, isokinetic knee muscle strength in simultaneous arthroscopic patients after having undergone an anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) with hamstring tendons reconstruction, 2) compare the results of ACL/PCL patients with the control group. Design: Controlled Laboratory Study. Materials and Methods: Results of 11 ACL/PCL patients had been matched with 22 uninjured control participants (CP). Prior to surgery, and minimum 2 years after it, functional assessment (Lysholm and IKDC 2000), mechanical knee joint stability evaluation (Lachman and “drawer” test) and isokinetic tests (bilateral knee muscle examination) had been performed. Different rehabilitation exercises had been used: isometric, passive exercises, exercises increasing the range of motion and proprioception, strength exercises and specific functional exercises. Results: After arthroscopy no significant differences had been found between the injured and uninjured leg in all isokinetic parameters in ACL/PCL patients. However, ACL/PCL patients had still shown significantly lower values of strength in relative isokinetic knee flexors (p = 0.0065) and extensors (p = 0.0171) compared to the CP. There were no differences between groups regarding absolute isokinetic strength and flexors/extensors ratio. There was statistically significant progress in IKDC 2000 (p = 0.0044) and Lysholm (p = 0.0044) scales prior to (44 and 60 points respectively) and after the reconstruction (61 for IKDC 2000 and 94 points for Lysholm). Conclusions: Although harvesting tendons of semitendinosus and/or gracilis from the healthy extremity diminishes muscle strength of knee flexors in comparison to the CP, flexor strength had improved. Statistically significant improvement of the knee extensor function may indicate that the recreation of joint mechanical stability is required for restoring normal muscle strength. Without restoring normal muscle function and strength, surgical intervention alone may not be sufficient enough to ensure expected improvement of the articular function. [ABSTRACT FROM AUTHOR]

The article presents the recommendations from the "International Society of Physiotherapy Journal" on the use of statistical inference through estimation.

Purpose: The aim of this study was to perform the translation and cross-cultural adaptation of the Achilles tendon Total Rupture Score (ATRS) into Polish version, and to evaluate its reliability and validity.Methods: The ATRS was translated into Polish language according to the Beaton recommendations. A total number of 71 patients previously treated surgically (from 2011 to 2015), due to the Achilles tendon rupture, were enrolled in this study. ATRS-Polish was performed twice within a period of 5-10 days. To evaluate test-retest reliability, intra-rater coefficient (ICC) was calculated. Construct validity was determined by the Spearman's rank coefficient correlation between the ATRS-Polish and a Polish version of EQ-5D-5L questionnaire.Results: Test-retest reliability was found to be excellent (ICC 0.9). The mean and standard deviation of the first and second assessment amounted 87.4 ± 14.0 and 88.4 ± 13.2, respectively. Construct validity analysis showed a strong correlation between the ATRS and the EQ-5D-5L score (r = - 0.69.) and moderate correlation between ATRS and actual comfort (r = 0.47).Conclusions and Perspectives: Polish version of the Achilles tendon Total Rupture Score was found to be reliable and valid.Level Of Evidence: Level II. [ABSTRACT FROM AUTHOR]