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The study assessed the effect of six weeks of biweekly upper and lower limbs' weighted-belt resisted sprint training (BRST) and weighted-vest resisted sprint training (VRST), or normal sprint training (NST) on muscle strength, speed, change of direction and handball-throwing velocity in young handball players. Twenty-seven pubertal male handball players aged 14.4 years were randomly assigned into BRST (n = 9), VRST (n = 8), and NST (n = 8) groups. Sprint ability (10-m and 30-m), squat jump (SJ), countermovement jump (CMJ), free-arm countermovement jump (CMJFA), standing long jump (SLJ), Five-jump test (FJT), change of direction and handball-throw velocity were assessed before and after a 6-week training in-season program. Within-group interactions showed that BRST improved all tests' performances (moderate-to-large). VRST improved sprint, SLJ, FJT and handball-throw velocity performances (small-to-large). NST improved only the change of direction performances (moderate). Between-groups comparison revealed that BRST improved all testing performances, except change of direction, compared with NST (large) and improved 30-m sprint, CMJFA, FJT and handball-throw velocity performance compared with VRST (moderate-to-large). In addition, VRST improved 30-m sprint, SJ and handball-throw velocity performances compared with NST (moderate-to-large). Throwing performance changes correlated with changes in sprint time and horizontal and vertical jump abilities (r = 0.40 to r = 0.69; p < 0.01). We conclude that while both resisted sprint training improved players' sprint, jumping and handball-throw performances, substantial improvements were recorded with the BRST compared to VRST and NST. Thus, BRST could be recommended to male U15 handball players as a valuable training method for developing physical fitness and skill performances., Competing Interests: The authors declare no conflicts of interest related to the paper., (Copyright © Institute of Sport – National Research Instutite.)

Introduction: Invasive pulmonary aspergillosis is a serious complication in hematology., Aim: Describe the prevalence, diagnostic aspects, therapeutic modalities, and evolution of the IPA cases occurring in patients with acute leukemia., Methods: Our study was retrospective including patients with acute leukemia who developed invasive pulmonary aspergillosis during the period January 2009 and December 2020 at the hematology department in south Tunisia. The IPA was defined in three levels of probability according to the criteria of the EORTC / MSG 2019., Results: We collected 127 patients who presented with Invasive pulmonary aspergillosis. Sixty-three percent of our patients had acute myeloid leukemia. The diagnosis of invasive pulmonary aspergillosis was during the induction course in 76% of cases. Twenty-seven of our patients had chest pain. The chest Computed tomography (CT) scan showed the Halo sign in 89% of cases. The Aspergillus galactomannan antigen was positive in 38% of cases. Extrapulmonary aspergillosis involvement was noted in 18% of cases: IPA was possible and probable respectively in 59% and 41% of cases. All patients treated with Voriconazole with a favorable response in 54% of cases. The mortality rate was 46%. The overall survival at week 12 was 56%., Conclusion: The morbidity and mortality of patients who developed invasive pulmonary aspergillosis with acute leukemia in our series were high. We need to improve our strategy for early diagnosis and management.

This study aimed to investigate azole resistance mechanisms in Aspergillus flavus, which involve cyp 51A and cyp 51B genes. Real-time Reverse Transcriptase qPCR method was applied to determine the overexpression of cyp 51A and cyp 51B genes for 34 A. flavus isolates. PCR sequencing of these two genes was used to detect the presence of gene mutations. Susceptibility test found sensitivity to voriconazole (VOR) in all strains. 14.7% and 8.8% of isolates were resistant to itraconazole (IT) and posaconazole (POS), respectively, with a cross-resistance in 5.8%. For the double resistant isolates (IT/POS), the expression of cyp 51A was up to 17-fold higher. PCR sequencing showed the presence of 2 mutations in cyp 51A: a synonymous point mutation (P61P) in eight isolates, which did not affect the structure of CYP51A protein, and another non synonymous mutation (G206L) for only the TN-33 strain (cross IT/POS resistance) causing an amino acid change in the protein sequence. However, we noted in cyp 51B the presence of the only non-synonymous mutation (L177G) causing a change in amino acids in the protein sequence for the TN-31 strain, which exhibits IT/POS cross-resistance. A short single intron of 67 bp was identified in the cyp 51A gene, whereas three short introns of 54, 53, and 160 bp were identified in the cyp 51B gene. According to the models provided by PatchDock software, the presence of non-synonymous mutations did not affect the interaction of CYP51A and CYP51B proteins with antifungals. In our study, the overexpression of the cyp 51A and cyp 51B genes is the primary mechanism responsible for resistance in A. flavus collection. Nevertheless, other resistance mechanisms can be involved., (© 2024 Dhoha Ghorbel et al., published by Sciendo.)

Objective: Our study aimed to investigate the association between cytochrome P450 1A1 (CYP1A1) polymorphisms (T3801C and A2455G) and acute lymphoblastic leukemia (ALL) risk, considering genetic models and ethnicity., Materials and Methods: PubMed, Embase, Web of Knowledge, Scopus, and the Cochrane electronic databases were searched using combinations of keywords related to CYP1A1 polymorphisms and the risk of ALL. Studies retrieved from the database searches underwent screening based on strict inclusion and exclusion criteria., Results: In total, 2822 cases and 4252 controls, as well as 1636 cases and 2674 controls of the C3801T and A2455G variants of CYP1A1, respectively, were included in this meta-analysis. The T3801C polymorphism of CYP1A1 significantly increases the risk of ALL, particularly those observed in Asian and Hispanic populations, independent of age. Similarly, the A2455G polymorphism of CYP1A1 plays a significant role in the susceptibility to ALL in all genetic models, except the heterozygous form. This association was observed mainly in mixed populations and in both children and adults (except in the heterozygous model)., Conclusion: Our comprehensive analysis indicates that the T3801 and A2455G polymorphisms of CYP1A1 may increase the risk of ALL depending on ethnicity. Therefore, both variants should be considered promising biomarkers for ALL risk. Further large-scale investigations are necessary to assess other factors, such as gene-gene or gene-environment interactions., (© 2024. The Author(s).)

Background: In sports sciences, normative data serve as standards for specific physical performance attributes, enhancing talent identification within a specific population. The aim of this study was to provide standard data for Agility-15 m, Ball-15 m tests, and skill index, considering maturation level, specifically age at peak height velocity (PHV). The study also investigated the relationship between relative performances in these tests and anthropometrics, jumping (squat jump [SJ], countermovement jump [CMJ]), and sprinting abilities (S-5 m, S-10 m, S-20 m, S-30 m) in young soccer players., Methods: The study involved 647 soccer players aged 11-18 years, categorized into three groups: pre-PHV, circum-PHV, and post-PHV. Statistical analysis was conducted using analysis of variance and Bonferroni post hoc testing to detect variations among maturation groups, and Pearson's correlation test to examine the relationship between factors., Results: Agility-15 m and ball-15 m performances among maturity groups showed significant differences (p < 0.01). Significant correlations were identified in pre-PHV group, between lower limb length and Agility-15 m (r=-0.23, p < 0.05) and between height and Ball-15 m (r=-0.23, p < 0.05). In post-PHV group, there was a correlation between body fat percentage (BF %) and Agility-15 m (r = 0.17, p < 0.05) and Ball-15 m (r = 0.21, p < 0.05). In all maturity groups, there were significant correlations between agility and sprint tests (S-5 m, S-10 m, S-20 m, and S-30 m) and muscle power (SJ and CMJ)., Conclusion: The study revealed that both speed and lower limb power significantly influence agility in young soccer players, providing valuable insights for coaches and practitioners to create tailored training plans and interventions for different age groups and maturity levels., (© 2024. The Author(s).)

Introduction: Imatinib is a first-line selective tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia. Although imatinib-induced hepatotoxicity may aggravate the patient's clinical condition and alter the treatment plan, the mechanism of imatinib-induced hepatotoxicity has rarely been investigated., Case Report: We report a 51-year-old man, suffering from acute toxic hepatitis after 5 months of imatinib treatment for chronic myeloid leukemia., Management and Outcome: The outcome was favorable after discontinuation of treatment with normalization of biological liver function after 12 weeks. The treatment was switched to nilotinib without any incidents., Discussion: Regular liver function test monitoring is recommended during imatinib treatment. In fact of acute hepatic toxicity, treatment with imatinib should be stopped in the case of cytolysis more than five times the upper limit of normal., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: perioperative anxiety in children may lead to psychological and physiological side effects. Clonidine is in increasing use in the pediatric population as an anxiolytic, sedative, and analgesic because of its central alpha2-adrenergic agonist effect. Our study aimed to evaluate the effect of clonidine in the prevention of perioperative children´s anxiety., Methods: we conducted a prospective controlled randomized double-blinded clinical trial including children aged between 2 and 15 years undergoing tonsillectomy surgery. The patients were randomly allocated to receive either an intranasal dose of clonidine (4 μg/kg) (clonidine group) or an equal volume dose of saline solution (control group) 30 minutes before entering the operating room. The level of anxiety assessed using the m-YPAS score was recorded before premedication, at the time of parent-child separation, and at the time of installation in the operating room. Acceptance of premedication, degree of sedation on entering the operating room as well as agitation on awakening, and sedation on arrival post-anesthesia care unit were noted. Adverse effects were recorded during the surgical procedure and in the postoperative recovery room., Results: the number of patients analyzed was 78 with 39 patients in each group. There were no signification differences in demographic data and premedication acceptance between the two groups. Levels of anxiety before any premedication were similar in the two groups. However, the anxiety level 30 minutes after premedication and in the operating room was significantly lower in the clonidine group (p<0.001). Children who received clonidine showed better sedation on entering the operating room (p=0.002) as well as postoperatively on entering the post-anesthesia unit care (p=0.006). The hemodynamic and respiratory parameters recorded were statistically comparable., Conclusion: intranasal clonidine is an interesting premedication to prevent perioperative children´s anxiety with few side effects., Competing Interests: The authors declare no competing interests., (Copyright: Mariem Keskes et al.)

Objective: Biclonal gammopathies (BGs) are rare situations characterized by the production of 2 monoclonal proteins. There are no available data on BGs in North Africa. We aimed to estimate the prevalence of BGs in our population and describe their clinical and laboratory features., Methods: We conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis., Results: A total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ± 10.87 years [range, 45-90 years]) were included. The main associated conditions were multiple myeloma (MM) (40%), BG of undetermined significance (BGUS) (34%), and lymphoproliferative diseases (23%). Only one-third of the patients had 2 monoclonal spikes on serum protein electrophoresis. The most common paraprotein combinations were immunoglobulin (Ig)G-IgG (25%) and IgG-IgA (23%) with different light chains in one-half of the cases. The mean follow-up was 25.6 months (median, 12 months). No BGUS evolved into a malignant disease., Conclusion: BGs are rare in clinical laboratory routine but must be accurately identified by the pathologist. Our cohort is characterized by a high prevalence of BGUS compared with MM., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cerebral venous thrombosis is a rare consequence of lumbar punctures for intrathecal therapy. We report a patient treated for diffuse large B cell lymphoma with cerebral venous thrombosis after intrathecal Methotrexate administration. In this patient, intrathecal treatment was discontinued and he was successfully treated with high-dose low-molecular-weight heparin subcutaneously. Haematologist must be aware about neurological symptoms of cerebral venous thrombosis as a complication of lumbar puncture especially among patients with high coagulopathy state. If neurological symptom occurs, patient should be referred early to neurologist to avoid fatal outcome and neurological deficit.

Introduction: Langerhans cell sarcoma (LCS) is a very rare malignant tumor of Langerhans cells that may metastasize to many organs. The diagnosis of this tumor is difficult and its prognosis is poor., Aim: To report the difficulty to diagnose LCS, and discuss therapeutic management of this rare entity., Case Presentation: We report a case of LCS in a 52-year-old man who presented with an axillar lymphadenopathy. The diagnosis of nodular sclerosis type Hodgkin's disease was established after histologic examination. The patient was treated with chemotherapy (ABVD regimen: Doxorubicin, Bleomycin, Vinblastine, Dacarbazine) and radiotherapy with a partial response. However, disease recurrence was observed and histological analysis confirmed the diagnosis of Langerhans cell sarcoma. A revision of the initial histological examination concluded to the diagnosis of sarcoma from the beginning. We chose the ESHAP (Etoposide, Methylprednisolone, Aracytine, Cisplatin) regimen and clinical improvement of LCS was obtained after 2 cycles but the patient had a fatal outcome and died by disease progression., Conclusion: Because of its rarity, diagnosis is difficult and an optimal treatment strategy for this disease has not yet been identified. Polychemotherapy can be an effective modality for the treatment of LCS.

Introduction: Non-Hodgkin lymphoma induced by imatinib, as a tyrosine kinase inhibitor, is a rare complication., Case Report: A 54-year-old female with a history of chronic myeloid leukemia (CML) was treated with imatinib as first-line therapy. The patient achieved a profound molecular response with treatment-free remission after five years but lost major molecular responses. A second deep molecular remission was again achieved. Nine years after imatinib therapy, the patient developed odynophagia and rhinorrhea. Physical examination revealed enlarged tonsils with a tumor-like appearance without palpable lymph nodes. Immunohistochemical examination of the tonsils revealed a large B-cell lymphoma. According to Naranjo's algorithm, the causality relationship with the drug is possible with a score of 3., Management and Outcome: Imatinib was discontinued. The lymphoma was treated with rituximab and chemotherapy., Discussion: Non-Hodgkin's lymphoma is a rare side effect of tyrosine kinase inhibitors and highlights the importance of follow-up CML patients.

We aimed to describe the clinical and biological characteristics and the prognosis of patients presenting with an additional light chain (LC) band along with a complete monoclonal protein on immunofixation (IF).An 8-year descriptive study was conducted to assess all cases with confirmed monoclonal gammopathies (MG). We studied those with an entire M-protein with 2 bands of LC of the same isotype based on the results of IF. Data were collected from patients' files.Among 548 cases of MG, we found 32 cases (5.8%) with an additional LC band. We included 28 patients (5%) with a confirmed diagnosis of multiple myeloma (MM). The m/f ratio was 2.5 with a median age of 63 years [32-80 years]. All MM patients had anemia, 16 (57%) had renal failure, 14 (50%) had lytic lesions, 9 (32%) received hemodialysis, and 7 (25%) had hypercalcemia. The free-kappa-lambda ratio was abnormal in all cases: median = 0.07 [0.002-58.57]. The mean overall survival (OS) was 22 months ± 38.76.Fifteen MM patients (48%) received chemotherapy, and 7 (22%) autologous stem cell transplants (SCT). Patients who received SCT had an OS higher than those who received other treatments (p = 0.038). OS was low in patients with high β2microglobulin levels (rho = -0.791; p = 0.001), and abnormally low free-kappa-lambda ratio (rho = -0.852;p = 0.04).The presence of an additional LC band with a complete monoclonal protein seems to identify newly diagnosed MM patients with poor outcomes and frequent renal impairment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study was to compare physical and hormonal responses of seventeen elite rugby sevens players over a 6-week intense training block (IT) and a consecutive 2-week tapering period (TAP), using a fatigue cut-off score of 20 as a potential moderating variable. Training was monitored by daily training load (TL) and strain (TS) (using the session rating of perceived exertion [sRPE]) and also the weekly total score of fatigue (TSF; 8-item questionnaire tool). Testing and 24 h urinary cortisol (CL), cortisone (CN), adrenaline (AD) and noradrenalin (NAD) concentrations were also analysed before (T0) and after IT (T1) and after the TAP (T2). Players were assigned to group 1 with a TSF above 20 (G1 > 20, n = 9) and group 2 with a TSF below 20 (G2 < 20, n = 8) according to the French Society for Sports Medicine guidelines. TSF (effect size [ES] from 1.17 to 1.75), TL (ES from 0.81 to 1.06) and TS (ES from 1.23 to 1.40) were higher in G1 > 20 than in G2 < 20 over IT. Likewise, performance standards (ES from 1.58 to 2.61) and AD levels were lower (ES = 3.20), whereas CL and CL/CN ratio (ES from 1.60 to 3.47) were higher in G1 > 20 than in G2 < 20. After the TAP, TSF, TL and TS returned to baseline values for both groups, with an increase in performance standards and normalization in hormone levels. We suggest that a TSF greater than or equal to 20 could be considered as a fatigue threshold generating hormone disturbance and performance decrement, making it a potentially useful preventive and complementary training monitoring tool., Competing Interests: None., (Copyright © Biology of Sport 2023.)

Background: The 6-min walk test (6MWT) provides information regarding functional capacity, response to therapy and prognosis in a variety of chronic cardiovascular disorders. Variability in body size and composition, particularly in obese people, confounds the six-minute covered distance (6MWD). The aim of the present study was to adopt allometric models to identify the most appropriate body size/shape; i.e., body mass (BM), body height (BH), body mass index (BMI) and estimated fat-free mass (FFM); associated with the 6MWD in 190 young girls with obesity., Methods: Nonlinear allometric modeling was used to calculate common body size exponents for BM, BH, BMI and FFM. In a validation sample of 35 age-matched obese girls, these allometric exponents were used prospectively., Results: The point estimates for the size exponents (95% confidence interval) from the separate allometric models were: BM 0.23 (0.19-0.27), BH 0.91 (0.78-1.03), BMI 0.33 (0.23-0.44) and FFM 0.28 (0.24-0.33). The presence of significant residual size correlations for 6MWD/BH -0.91 indicates that the influence of body size was not correctly partitioned out. In the validation group, the correlations between 6MWD BM -b and BM, 6MWD BMI -b and BMI, and 6MWD FFM -b and FFM using the established exponents were not statistically different from zero (r = 0.01), implying that participants in the allometric investigation were not penalized based on their BM, BMI, or FFM., Conclusion: We conclude that BM, BMI, BH and FFM, as indicators of body size/shape, are the most valid allometric denominators for the scaling of 6MWD in a group of young girls with obesity.

Introduction: Tyrosine kinase inhibitor had changed the prognosis of chronic myeloid leukemia (CML) and the overall survival had reached 95%. Unfortunately, adverse events (AEs) remain an obstacle to following successful treatment in CML impairing the quality of life and sometimes endangering the lives of patients. To this end, we show this clinical case to discuss strategies to deal with rare AEs in a way to preserve the patient's life and to maintain not only a good response to treatment but also confidence and compliance of the patient., Case Report: We report the case of a 57-year-old woman diagnosed with CML at the chronic phase who developed rare life-threatening hepatotoxicity (major cytolysis and prothrombin time fall) secondary to Nilotinib used as second-line treatment. This complication settled despite an optimal molecular response., Management and Outcome: We discuss below the follow-up and management in our center and according to the literature with more sophisticated pharmacological methods., Discussion: Although we used to monitor disease molecular response to treatment, we need solutions and manuscripts for monitoring drug dose parameters to avoid unusual dangerous effects risking the patient life. We conclude that monitoring the disease as well as the treatment pharmacokinetics is mandatory to better carry on CML patients.

Aim: This study was carried out to assess the minimal residual disease in Tunisian patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors in routine clinical practice, to recognize potentially eligible carrier for treatment discontinuation, based on a molecular response (MR)., Patients and Methods: A retrospective study was carried out in the Hospital University of Sfax, south of Tunisia from January 2016 to October 2020, including all CML patients in the chronic phase at diagnosis, treated with TKI (tyrosine kinase inhibitors) for a minimum duration of 6 months. Quantitative assessment of the BCR-ABL transcript was performed using the Cepheid Xpert BCR-ABL ultra-assay. Molecular response and outcome were evaluated, according to the European Leukemia Net guidelines., Results: A total of 162 CML patients were carried out. The median age was 50 years, the sex ratio M/F was 1.62. The rate of cumulative EMR; MMR and DMR was 80.8%; 73.8% and 55.9% respectively. According to the ELN criteria, 141 CML patients were evaluable. Optimal, suboptimal response and failure were noted in 81 (57.4%), 33(23.4%), and 27(19.1%) patients, respectively. Overall survival (OS) and progression-free survival (PFS) were 96.3% and 85%. Risk factors for an event (death/progression) were lack of EMR, MMR, and DMR (P < 0.05). Among 149 patients with sustained DMR; 14 (8.6%) CML patients have discontinued TKI therapy., Conclusion: Despite the limit of our study (duration and size), the available real-life molecular responses with TKI therapy should be considered to identify potentially CML patients eligible for discontinuation of TKI therapy.

Hemophilia is a rare constitutional hemorrhagic disorder. There is insufficient epidemiological data on hemophilia in Tunisia. To describe the epidemiological, clinical, therapeutic, and outcome of a cohort of patients with hemophilia in southern Tunisia. A retrospective study was conducted on patients with hemophilia at the Hemophilia Treatment Center of Southern Tunisia in Sfax over 38 years (from January 1982 to December 2020). Data were collected in a regional hemophilia registry of the South Tunisian center. We collected 141 cases of hemophilia, 85% of whom had hemophilia A and 15% had hemophilia B. The severe form represented 65%, followed by the moderate form at 25%. The prevalence of hemophilia was 4.4 in 100 000 population. Family history of hemophilia was found in 70%. The mean age of patients at diagnosis was 28 months. Hemophilia was detected in 87% of cases after hemorrhagic syndrome. Bleeding occurred mainly in hemarthrosis (73%), hematoma (70%), and visceral bleeding (28%). Intracranial bleeding occurred in 6% of cases. Thirty-six percent of patients were on prophylactic therapy. Hemophilic arthropathy was the most important orthopedic complication in our patients (38%). Inhibitory antibodies occurred in 16% of PWH. Transfusion-transmitted infections with HIV and hepatitis C were in 2 and 31% of cases, respectively. The prevalence of hemophilia is still underestimated in our center. The severe form of hemophilia is the most frequent. Hemophilic arthropathy was the most important complication in our patients. This showed that hemophilia is still a disabling disease in our country., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Primary plasma leukemia is defined by the presence of more than 20% plasma cells in the peripheral blood or number of circulating plasma cells greater than 2G/L. It has points in common with multiple myeloma and has certain characteristics, in particular its aggressiveness and poor prognosis. Through 02 cases diagnosed in the flow cytometry laboratory, the authors present the clinical, cytological and especially immunophenotypic features of this disease, with the emphasis on the role of flow cytometry in the diagnosis.

Purpose: To investigate differences in athletes' knowledge, beliefs, and training practices during COVID-19 lockdowns with reference to sport classification and sex. This work extends an initial descriptive evaluation focusing on athlete classification., Methods: Athletes (12,526; 66% male; 142 countries) completed an online survey (May-July 2020) assessing knowledge, beliefs, and practices toward training. Sports were classified as team sports (45%), endurance (20%), power/technical (10%), combat (9%), aquatic (6%), recreational (4%), racquet (3%), precision (2%), parasports (1%), and others (1%). Further analysis by sex was performed., Results: During lockdown, athletes practiced body-weight-based exercises routinely (67% females and 64% males), ranging from 50% (precision) to 78% (parasports). More sport-specific technical skills were performed in combat, parasports, and precision (∼50%) than other sports (∼35%). Most athletes (range: 50% [parasports] to 75% [endurance]) performed cardiorespiratory training (trivial sex differences). Compared to prelockdown, perceived training intensity was reduced by 29% to 41%, depending on sport (largest decline: ∼38% in team sports, unaffected by sex). Some athletes (range: 7%-49%) maintained their training intensity for strength, endurance, speed, plyometric, change-of-direction, and technical training. Athletes who previously trained ≥5 sessions per week reduced their volume (range: 18%-28%) during lockdown. The proportion of athletes (81%) training ≥60 min/session reduced by 31% to 43% during lockdown. Males and females had comparable moderate levels of training knowledge (56% vs 58%) and beliefs/attitudes (54% vs 56%)., Conclusions: Changes in athletes' training practices were sport-specific, with few or no sex differences. Team-based sports were generally more susceptible to changes than individual sports. Policy makers should provide athletes with specific training arrangements and educational resources to facilitate remote and/or home-based training during lockdown-type events.

Introduction: Functional variants of the Methylenetetrahydrofolate reductase ( MTHFR ) gene, the C677T and A1298C, have largely investigated in pharmacogenomics of Methotrexate (MTX) in acute lymphoblastic leukemia (ALL), yet the conclusions are inconsistent. In addition; most of these studies do not analyze haplotypes. Here, we investigate the MTHFR 677/1298 genotypes and the 677-1298 haplotype and characterize the MTX response in Northern African ALL patients., Methods: Genomic DNA was extracted from whole venous from a total of 28 patients with ALL. Genotyping were carried out with restriction fragment length polymorphism (RFLP). A toxicity score (TS) is calculated for each patient and correlate to the haplotype., Results: The allelic frequency of MTHFR 677T-1298C haplotype was 10.7% in ALL patients. According to the toxicity's score (TS) there was no significant differences between haplotype groups (p = 0.79): TS was higher with wild type of MTHFR (TS = 3.43; SEM ± 0.85) followed by combined genotype (677T-1298C) (TS = 2.67; SEM ± 0.88) and isolated variant (C677T or A1298C) (TS = 2.64; SEM ± 0.92)., Conclusion: Despite the limitation of this study; our results suggest that the MTHFR 677T-1298C haplotype is common in ALL and may be a promising HD-MTX chemotherapy-related adverse effects biomarker.

Objective: Our objective was to explore the training-related knowledge, beliefs, and practices of athletes and the influence of lockdowns in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: Athletes (n = 12,526, comprising 13% world class, 21% international, 36% national, 24% state, and 6% recreational) completed an online survey that was available from 17 May to 5 July 2020 and explored their training behaviors (training knowledge, beliefs/attitudes, and practices), including specific questions on their training intensity, frequency, and session duration before and during lockdown (March-June 2020)., Results: Overall, 85% of athletes wanted to "maintain training," and 79% disagreed with the statement that it is "okay to not train during lockdown," with a greater prevalence for both in higher-level athletes. In total, 60% of athletes considered "coaching by correspondence (remote coaching)" to be sufficient (highest amongst world-class athletes). During lockdown, < 40% were able to maintain sport-specific training (e.g., long endurance [39%], interval training [35%], weightlifting [33%], plyometric exercise [30%]) at pre-lockdown levels (higher among world-class, international, and national athletes), with most (83%) training for "general fitness and health maintenance" during lockdown. Athletes trained alone (80%) and focused on bodyweight (65%) and cardiovascular (59%) exercise/training during lockdown. Compared with before lockdown, most athletes reported reduced training frequency (from between five and seven sessions per week to four or fewer), shorter training sessions (from ≥ 60 to < 60 min), and lower sport-specific intensity (~ 38% reduction), irrespective of athlete classification., Conclusions: COVID-19-related lockdowns saw marked reductions in athletic training specificity, intensity, frequency, and duration, with notable within-sample differences (by athlete classification). Higher classification athletes had the strongest desire to "maintain" training and the greatest opposition to "not training" during lockdowns. These higher classification athletes retained training specificity to a greater degree than others, probably because of preferential access to limited training resources. More higher classification athletes considered "coaching by correspondence" as sufficient than did lower classification athletes. These lockdown-mediated changes in training were not conducive to maintenance or progression of athletes' physical capacities and were also likely detrimental to athletes' mental health. These data can be used by policy makers, athletes, and their multidisciplinary teams to modulate their practice, with a degree of individualization, in the current and continued pandemic-related scenario. Furthermore, the data may drive training-related educational resources for athletes and their multidisciplinary teams. Such upskilling would provide athletes with evidence to inform their training modifications in response to germane situations (e.g., COVID related, injury, and illness)., (© 2021. The Author(s).)

Introduction: Nilotinib, as the second generation of tyrosine kinase inhibitor, has significant efficacy in patients with chronic myeloid leukemia resistant or intolerant to Imatinib. Aplastic anemia induced by tyrosine kinase inhibitors is an uncommon complication., Case Report: A 34-year-old female case with CML in the chronic phase was treated with Imatinib in first-line therapy. Nilotinib was switched because of failure to achieve complete cytogenetic response at 6 months following Imatinib. Three years with Nilotinib, the patient developed a persistent pancytopenia grade 4 while a major molecular response was achieved., Management & Outcome: Nilotinib was discontinued. However, the hematologic finding of the patient had not recovered after three months. A bone marrow biopsy showed marked hypocellularity and fatty tissue without evidence of myelofibrosis. Immunosuppressive therapy was started. Unfortunately, the patient died due to septic and hemorrhagic shock nine months after Nilotinib interruption. According to Naranjo's algorithm, the causality relationship with the drug is probable with a score of 5., Discussion: Aplastic anemia is an uncommon adverse event of tyrosine kinase inhibitors but it can be a fatal complication. The early diagnosis of aplastic anemia related to Nilotinib therapy is needed to avoid further detrimental effects of the drug.

Introduction: Palliative care is an approach that improves the quality of life of patients with advanced disease., Objective: The aim of this study is to evaluate the process of palliative care in patients with hematologic malignancies., Methods: In this prospective observational study, we included patients with hematologic malignancies who received palliative care over a 12 month period from June 1, 2019, to May 31, 2020 at the day care hospital of the hematology department in University Hospital of Sfax, Tunisia. Blood transfusion was used to relieve symptoms of anemia and bleeding., Results: Fifty-five patients were included. The median age was 68 years. Forty-three percent of patients were diagnosed with acute leukemia and 41.8% with myelodysplastic syndrome. Red cell and platelet transfusions were indicated in 94.5% and 36.3% of cases respectively. Patients reported improvement after blood transfusion in 50% of cases. Twenty-five transfusion reactions (45%) were noted. Fever was noted in 33 patients (60%), with documented sites of infection in 84.8% of them. Pulmonary infection was frequently noted (50%). Antimicrobial treatment was prescribed in all febrile cases. Pain was reported in 22 patients and in 77.5% of these cases, it was nociceptive. Patients who received analgesics showed clinical improvement in pain in 81% of cases. Anorexia with malnutrition was reported in 23% of cases which was treated with enteral nutrition in 75% of cases. Sleep disturbance (20 patients), anxiety (7 patients), and depression (4 patients) were mentioned respectively., Conclusion: Palliative care in hematology should be a multidisciplinary care approach with a global management of the various physical, psychological and sociological complications., (Copyright © 2021 Société française de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Biclustering is a non-supervised data mining technique used to analyze gene expression data, it consists to classify subgroups of genes that have similar behavior under subgroups of conditions. The classified genes can have independent behavior under other subgroups of conditions. Discovering such co-expressed genes, called biclusters , can be helpful to find specific biological features such as gene interactions under different circumstances. Compared to clustering, biclustering has two main characteristics: bi-dimensionality which means grouping both genes and conditions simultaneously and overlapping which means allowing genes to be in more than one bicluster at the same time. Biclustering algorithms, which continue to be developed at a constant pace, give as output a large number of overlapping biclusters. Visualizing groups of biclusters is still a non-trivial task due to their overlapping. In this paper, we present the most interesting techniques to visualize groups of biclusters and evaluate them., (© 2021 Haithem Aouabed et al., published by De Gruyter, Berlin/Boston.)

Introduction: Pulmonary toxicity causally related to Imatinib (IM) therapy is uncommon in patients with chronic myeloid leukemia., Case Report: A 61-year-old patient with chronic myeloid leukemia was treated with IM at 400 mg daily dose. One month within IM, he developed skin lesions and then acute dyspnea and non-productive cough. Chest radiograph and high-resolution lung computed tomography (CT) revealed bilateral reticulonodular infiltration in both lungs. According to Naranjo's algorithm, the causality relationship with the drug is probable with a score of 7. The pharmacovigilance investigation was carried out and implicated IMManagement & outcome: IM was discontinued and started steroid therapy (Prednisolone®) at 1 mg/kg daily. Two weeks after, the dyspnea, and abnormal X-ray and CT findings are improved., Discussion: The early diagnosis of pulmonary toxicity related to IM therapy is needed to avoid further determinal effects of the drug.

Introduction: Diagnoses of myeloproliferative disorder is based on molecular marker. Chronic Myeloid Leukemia and Myeloproliferative neoplasms were considered mutually exclusive and co-existence of BCR/ABL1 and JAK2 mutation is a rare phenomenon., Case Report: Here, we present two cases of co-existence of BCR-ABL and JAK2V617F positivity. We characterize the course of the disease, mainly the minimal residual disease. Management and outcome: The two cases was initially managed as Chronic Myeloid Leukemia and treated by TKI inhibitors. The first one was diagnosed in 2010. He started the first line of TKI, and then switched to second line without obtaining a major molecular response. Hence he was tested for JAK2V617F mutation and positivity was diagnosed. The second patient showed Chronic Myeloid Leukemia phenotype with coexistence of BCR/ABL1 and JAK2 mutation at diagnosis. Molecular monitoring reveals a high BCR-ABL1 transcript level (20%) at the last follow-up (12 months)., Discussion: Ours results highlight that JAK2V617F/BCR-ABL double positivity may be a potential marker of resistance in Chronic Myeloid Leukemia and clonal molecular analysis is mandatory to elucidate the mechanism. Moreover, the combination of JAK and TKI inhibitors might be effective and potentially be guided by molecular monitoring of minimal residual disease.

Background: Methotrexate (MTX) is a key drug in acute lymphoblastic leukemia (ALL) treatment; it inhibits DNA replication by blocking the conversion of 5, 10 Methylenetetrahydrofolate to 5-methylene tetrahydrofolate by methylenetetrahydrofolate reductase (MTHFR). Variants of the Methylenetetrahydrofolate reductase (MTHFR) and MTX related toxicities were largely investigated in several populations, nevertheless, the results are conflicting., Objective: This study aimed to assess the prevalence of MTHFR SNVs: C677>T and A1298>C in Tunisian patients with ALL and the relation to the frequency of drug-induced complications., Methods: 28 ALL patients were included in the study. They were treated according to EORTOC, in which a high dose of MTX (HDMTX) was prescribed. A toxicity score (ST) is calculated for each patient, summing the grades of toxicities. Genotyping of MTHFR variants was done with a PCR-based restriction fragment length polymorphism assay., Results: The toxicity's score (TS) was higher with C677T variant compared to wild genotype (C677C) (TS = 4; IC95% [-2.65-13.32] versus TS = 2.5; IC95% [1.65-4.55], respectively; p = 0.2); but lower with the A1298C mutation compared to those with the wild genotype (A1298A) (TS = 2.5; IC95% [0.48-4.77], versus TS =3; IC95% [1.9-5.69], p = 0.4). HDMTX-related toxicity is associated with the 677CT genotype in ALL patients (RR = 1.41, p = 0.2); not for the A1298C [OR = 0.46, [0.08-2.61], p = 0.18]., Conclusion: Our preliminary findings highlight the impact of the C677T variant of MTHFR, but not the A1289C; in HD-MTX chemotherapy-related adverse effects in younger Tunisian ALL.

Background: Acute lymphoblastic leukemia (ALL), a common blood cancer, is characterized by the interaction between genetic and environmental factors. Several variants of the Methylenetetrahydrofolate reductase (MTHFR), mainly the C677T (rs1801133), may affect susceptibility to ALL., Aim of the Study: The authors conducted this case-control study to evaluate the relationship between this variant of the MTHFR gene and the risk of ALL., Materials and Methods: Forty-one patients with ALL and 35 non-ALL controls recruited in this study were genotyped utilizing polymerase chain reaction-restriction fragment length polymorphism methodology., Results: The MTHFR 677CT genotype was significantly more frequently found in patients with ALL having a 2-fold increase in risk (P <0.01)., Conclusion: Our results suggest that rs1801133 of MTHFR is a predictive risk marker to ALL in Tunisian ALL., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: To develop a 6-minute walk-distance (6MWD) reference equation for children and adolescents with obesity, and to assess its determinant factors., Methods: A cross-sectional study using mixed linear and multiple regression models was conducted in 497 children (235 girls and 262 boys) aged 6-18 years with a body mass index (BMI) greater than 97th percentile. Anthropometrics and a 6-minute walk test (6MWT) were performed., Results: Mean 6MWD was 547 ± 86 m for girls and 575 ± 96 m for boys, which averaged ~80% of a reference normal-weight population matched for age and ethnicity. Age, weight and BMI were positively correlated with 6MWD whereas waist and hip circumferences (WC and HC, respectively) were negatively correlated with 6MWD for both genders. The combination of age, height, BMI and HC explained 69% of the 6MWD variability in the equation for the whole population. Moreover, the combination of age, height, HC as well as the combination of age, height, BMI and WC explained 67% and 75% of the variability in the girls' and boys' equations, respectively., Conclusion: This 6MWD reference equation, which was influenced by abdominal obesity markers in a gender-specific way, extends and enhances scientific knowledge and provides useful predictive tools for the care of obese children., (© 2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

One of the main methods to analyze gene expression data is biclustering, a nonsupervised technique, which consists of selection subgroups of genes that co-expressed under subgroups of experimental conditions. A large number of biclustering algorithms have been developed to classify gene expression data. These algorithms can give as output a large number of overlapped biclusters, whose visualization still requires deeper studies. We present VisBicluster, a web-based interactive visualization tool for displaying biclustering results. The developed visualization technique consists of laying out the generated biclusters in a two-dimensional matrix where each bicluster is represented as a column and each overlap between a set of biclusters is represented as a row. A search interface for the user is developed to query the matrix of bicluster intersection and visualize the results matching the queries. Our tool supports many interactive features such as sorting, zooming, and details-on-demand. We proved the usefulness of VisBicluster with biclustering results from real and synthetic datasets. Besides, we performed a user study with 14 participants to illustrate the clarity and simplicity of overlap representation with our tool.

Background: The P-glycoprotein (P-gp) is one of the mechanisms of Imatinib (IM) resistance in chronic myeloid leukemia (CML). P-gp has been identified as an efflux pump involved in releasing of IM outside CML cells. To date, the P-gp involvement in the IM resistance development was not completely understood. Therefore, the present study aimed at measuring the P-gp expression level on lymphocytes from Tunisian patients with CML and correlating this level with a molecular response to IM., Method: The expression of P-gp on peripheral blood lymphocytes from 59 Tunisian patients with CML (27 IM responder patients vs 32 IM non-responder patients) was evaluated by flow cytometry., Result: Our finding showed significantly positive expression of P-gp in the lymphocytes from the IM non-responder group when compared to the IM-responder group (P = .001). In IM non-responder CML patients, the comparison between CCyR achievers and non-achievers showed a high mean fluorescence intensity (MFI) of P-gp expression in patients who did not achieve their CCyR (P = .001). The comparison between patients with primary and secondary resistance to IM showed an increasing MFI value in patients with primary resistance to IM (P = .001). Besides, the comparison between nilotinib-treated and dasatinib-treated patients proved a high value of MFI in nilotinib-treated patients (P = .001)., Conclusion: The overexpression of P-gp on lymphocytes has significantly correlated with the failed molecular response to IM in patients with CML., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Selmi, MA, Sassi, RH, Yahmed, MH, Giannini, S, Perroni, F, and Elloumi, M. Normative data and physical determinants of multiple sprint sets in young soccer players aged 11-18 years: Effect of maturity status. J Strength Cond Res 34(2): 506-515, 2020-The aims of the study were: (a) to establish normative data for repeated-sprint sets (RSS) test based on the maturity status (age at peak height velocity [PHV]) and (2) to investigate the relationship between anthropometrical variables (stature, sitting height, body mass, and body fat percentage), RSS (2 × 5 × 20 m with 15-second recovery between sprints and 1-minute recovery between sets), and fitness tests {squat jump, countermovement jump, standing long jump, standing triple jump, 5-jump test, and 20-m shuttle run (multistage shuttle run test [MSRT])}. Young male soccer players (n = 262; age: 14.5 ± 2.9 years) were evaluated and classified into 4 groups according to their maturity status: pre-PHV, circum-PHV1, circum-PHV2, post-PHV. An analysis of variance and Bonferroni post hoc were used to determine maturity group differences (p ≤ 0.05), whereas Pearson's correlation was used between variables. Repeated-sprint sets' indices (sum of sprint times [SST] and best sprint time [BST]) were significantly different between the maturity groups. Significant correlations between SST with body mass (from -0.73 to -0.33) and MSRT (from -0.49 to -0.30) among each maturity group were found. With the different maturity groups, correlations between SST (s), BST (s), and vertical jump (cm) (r = -0.63 to -0.25 and r = -0.68 to -0.23) and horizontal jump (m) (r = -0.70 to -0.38 and r = -0.63 to -0.43) were observed. Repeated-sprint sets' values improve during maturation of young soccer players and the correlations between RSS and fitness tests vary through the maturity groups. This information could be useful for the coach to identify talent and to prescribe specific physical training to improve performance.

Background: This work aimed to evaluate oxidative stress in chronic myeloid leukemia (CML) patients treated with tunisian (IM) vs controls and in CML patients with resistance to IM vs patients without resistance to IM., Methods: The study included 40 CML patients and 34 controls. Of 40 patients with CML, 26 patients were developed in resistance to IM. The oxidant/antioxidant markers were evaluated by spectrophotometric methods for all used samples., Results: For CML patients, increased malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels were found compared to controls (P < .001; P = .01). Higher catalase (CAT) activity (P = .048) and lower superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, reduced Glutathione (GSH) and vitamin C levels were found in CML patients (P < .001). The comparison between the resistant vs no-resistant CML patients revealed higher MDA level (P = .02) and CAT and SOD activities in IM-resistant patients (P = .04, P = .03). GPx activity was reduced (P = .04). Furthermore, increased mean ratio of MDA/GSH, MDA/GPx, and SOD/(GPx + CAT) was found in IM-resistant patients as compared with no-resistant (P = .01, P = .01, P = .035). The mean ratio of GPx/GSH in the IM-resistant CML patients was lower than in IM no-resistant one (P = .039). For IM-resistant patients, we found negative correlation between MDA level and the ratio SOD/(CAT + GPx) (r = -0.46, P = .002); and positive correlation between SOD and (CAT + GPx) activities (r = 0.38, P = .06) and between GSH level and GPx activity (r = 0.53, P = .01)., Conclusions: Our results have shown a highly disturbed oxidative profile in IM-resistant CML patients as compared to no-resistant. The H 2 O 2 has a key role in the resistance to IM treatment., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Optic nerve infiltration is relatively rare in acute lymphoblastic leukemia. We present a case of a -53 year-old-man who was diagnosed with T- acute lymphoblastic leukemia (ALL). The patient was treated with ALL national protocol and the central nervous system (CNS) prophylactic management. On treatment, the patient presented with sudden severe vision deterioration of both eyes. Fundoscopic examination of the eye and magnetic resonance imaging of the orbits were in favor of an infiltration of the optical nerve. An isolated extramedullary relapse of the optical nerve was retained. The patient was treated with salvage chemotherapy systematic and intrathecal. Waiting forthe beginning of radiotherapy, the patient presented a bone marrow relapse. He died of a severe hemorrhagic syndrome. Conclusion: Optic nerve leukemic infiltration has a severe prognosis. Ophthalmic assessment is essential in patients with ALL in order to diagnose an early ocular involvement and the patient's vision can be preserved if treatment is initiated promptly.

Context: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, mainly the C677T, have been implicated as risk factors for several cancers as the acute lymphoblastic leukemia (ALL). In addition, a potential effect of such variant on the efficacy of methotrexate (MTX) has been reported., Objective: In this study, we evaluated the impact of the C677T variant of MTHFR on MTX-related toxicity in ALL patients from Tunisia; to provide new insights for a personalized therapy based on the human genotype., Materials and Methods: Genotyping was carried out with restriction fragment length polymorphism (RFLP) on blood samples from a total of 35 younger patients; suffering from ALL., Results: In the ALL patients, the MTHFR 677CT genotype confers a greater risk of toxicity with 1.3 times as relative risk mainly the hepatic toxicity when compared with MTHFR 677CC., Conclusion: Our findings suggest that C677T polymorphism of MTHFR seems to be a good marker for MTX-related toxicity in ALL.

Background: Emotional intelligence refers to how individuals deal with intrapersonal or interpersonal emotional information and how a subject identifies, expresses, understands, regulates, and uses his/her own emotions or those of others. The purpose of the present study was to validate the Arabic version of the "Profile of Emotional Competence" (PEC) questionnaire., Methods: A sample of 285 Tunisian participants (153 men and 132 women) was recruited, age range: 12-18 years (15.2±2.4 years). The participants were prospectively classified into the following two groups: athletes (n=101) and nonathletes (n=184)., Results: Findings of the present study indicated that the Arabic version of the PEC questionnaire has good psychometric properties. The Cronbach's a suggested that all subscales had adequate internal consistency. Test-retest reliability was excellent. The correlations between interpersonal and intrapersonal subscales were low to moderate (from 0.37 to 0.59), except for the regulation interpersonal, utilization interpersonal, and utilization intrapersonal subscales, which showed negligible correlations with the other subscales. The two-factor solution (interpersonal and intrapersonal competence models) accounted for 62.1% of variance. All subscales loaded on the expected factor, except for the utilization intrapersonal and regulation interpersonal subscales, which did not yield a satisfactory loading. Age and athletes' status impacted on all the PEC dimensions, except for some subscales., Conclusion: Finally, psychologists and practitioners in the Arab world could use the PEC questionnaire as a valid and reliable instrument for planning ad hoc interventions., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Cutaneous leishmaniasis (CL) is a major disease in many parts of the world. Since no vaccine has been developed, treatment is the best way to control it. In most areas, antimonial resistance whose mechanisms have not been completely understood has been reported. The main aim of this study is gene expression assessing of J - binging protein 1 and J - binding protein 2 in clinical Leishmania major isolates. The patients with CL from central and north Iran were considered for this study. The samples were transferred in RNAlater solution and stored in - 20 °C. RNA extraction and cDNA synthesis were performed. The gene expression analysis was done with SYBR Green real-time PCR using ∆∆CT. Written informed consent forms were filled out by patients, and then, information forms were filled out based on the Helsinki Declaration. Statistical analysis was done with SPSS (16.0; SPSS Inc, Chicago) using independent t test, Shapiro-Wilk, and Pearson's and Spearman's rank correlation coefficients. P  ≤ 0.05 was considered significant. The gene expression of JBP1 and JBP2 had no relation with sex and age. The JBP1 gene expression was high in sensitive isolates obtained from north of the country. The JBP2 gene expression was significant in sensitive and no response-antimonial isolates from the north, but no significant differences were detected in sensitive and resistant isolates from central Iran. Differential gene expression of JBP1 and JBP2 in various clinical resistances isolates in different geographical areas shows multifactorial ways of developing resistance in different isolates., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.

Purpose: We aimed to evaluate therapeutic results of radiotherapy for gastric mucosa-associated lymphoid tissue (MALT) lymphomas., Patients and Methods: We reviewed retrospectively the records of 11 patients presenting with gastric MALT lymphoma treated between 1993 and 2014. Patients with low-grade lymphoma in failure after helicobacter eradication had exclusive gastric external radiotherapy. Chemotherapy followed by radiotherapy were indicated in case of high grade lymphoma. Radiotherapy doses range between 30 and 40Gy (2Gy per fraction, five fractions per week)., Results: All tumours were IE stage. Seven patients with low-grade lymphoma had radiotherapy. Four patients with high-grade lymphoma received chemotherapy then radiotherapy. Ten patients are in complete remission after treatment achievement. Five and 10 years disease-free survival are 100%. No severe toxicity was seen., Conclusion: Eradication of Helicobacter pylori is the mainstay of treatment of gastric MALT. External irradiation is an effective and well-tolerated treatment modality in case of resistance to helicobacter eradication., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy, but it is associated with serious toxicities in a considerable number of patients., Objectives: The aim of the current study was to determine which variables were associated with MTX toxicity in children, adolescents and young adults with ALL., Material and Methods: In this prospective study, 35 patients with newly diagnosed ALL, treated according to the 58951 European Organization for Research and Treatment of Cancer - Children's Leukemia Group (EORTC-CLG) protocol, were prospectively enrolled. Toxicity data was collected objectively after each high-dose methotrexate (HD-MTX) course. The risk factors of MTX toxicity were determined using multiple linear regression analysis, with age, gender, immunophenotype, risk group, plasma MTX levels, plasma homocysteine (HCY) levels, and MTHFR C677T included as independent variables., Results: Twenty-five (71.4%) patients experienced toxicity on at least 1 course of HD-MTX. In the univariate linear regression, the global toxicity score was associated with a significant rise in plasma HCY concentrations within 48 h after MTX administration (β = 0.4; R2 = 0.12; p = 0.02). In the multiple regression model, the global toxicity score was significantly associated with a higher MTX plasma levels at 48 h (β = 0.5; R2 = 0.38; p = 0.001) and CT 677 MTHFR genotype (β = 0.3; R2 = 0.38; p = 0.01)., Conclusions: Routine monitoring of plasma MTX concentrations is essential to detect patients at a high risk of MTX toxicity. MTHFR C677T genotyping may be useful for predicting MTX toxicity.

Objective: In Tunisia, the management of Adult Hodgkin's Lymphoma (HL) has been standardized since 1999. We propose in this study to report the therapeutic results of the national protocol of adult HL treatment (MDH2008)., Patients and Methods: Our study is prospective multicenter interesting 444 patients followed for HL between July 2008 and June 2013 and treated according to the MDH2008 protocol. The median age of our patients was 30 years. B symptoms were present in 62.8 % of our patients. According to the Ann Arbor classification, our patients were in stages I, II, III and IV in 3 %, 42 %, 26 % and 29 %, respectively. The MDH2008 protocol is based on a strategy adapted to the therapeutic response to 2 cycles of chemotherapy., Results: Response≥75 % to 2 courses of chemotherapy was achieved in 43 % of patients and the response rate at the end of treatment was 92.1 %. Forty-eight patients (11.4 %) had primary failure. In the multi-variant study, bulky mediastinal mass (IMT≥0.35) was an independent predictive factor of primary failure (P: 0.000). Nineteen toxic deaths (4.35 %) were reported. The relapse rate was 7.8 %. Event free survival, relapse-free survival and overall survival at 5years were 75 %, 89 % and 90 %, respectively. Adaptation of the treatment to the 2 cycles response was effective in unfavorable early stages and advanced stages., Conclusion: Compared to MDH2002 (second version of Tunisian prospective protocol), the MDH2008 reduced the primary failure rate, the rate of toxic deaths with escalated BEACOPP and the rate of relapse in Tunisian patients., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology. Response (hematologic, cytogenetic, and molecular responses) and outcome-overall survival (OS), event-free survival (EFS), and progression-free survival (PFS)-were evaluated. The following prognostic factors were analyzed for their impact on the European leukemia net (ELN) response, OS, EFS, and PFS at 5 years: age, sex, leukocyte count, Sokal score, European Treatment and Outcome Study (EUTOS) score, CML phase, time to starting IM, and impact of adverse events. The median age was 45 years (3-85 years). Two hundred ten (51.2%) patients were male. Splenomegaly was present in 322 of the 410 (79%). Additional cytogenetic abnormalities were encountered in 25 (6.3%) patients. At diagnosis, 379 (92.4%) patients were in CP, 31 (7.6%) were in AP. The Sokal risk was low in 87 (22.5%), intermediate in 138 (35.7%), and high in 164 patients (41.9%). The EUTOS risk was low in 217 (74%), and high in 77 (26%) patients. The rates of cumulative complete cytogenetic response (CCyR), major molecular response (MMR), and molecular response 4/5 log (MR4.5) in CP/AP-CML patients were 72, 68.4, and 46.4%, respectively. The median time to reach CCyR, MMR, and MR4.5 was 6 months (3-51), 18 months (3-72), and 24 months (3-100), respectively. According to the ELN criteria, optimal, suboptimal response, and failure were noted in 206 (51.8%), 61 (15.3%), and 125 (31.4%) patients, respectively. Five-year event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) were 81, 90, and 90%, respectively. By multivariate analysis, AP, high EUTOS risk, and baseline WBC ≥ 150G/l remained independent predictive factors of non-optimal response to IM. The adverse events (AE) of IM were moderate and tolerable. With the caveats that the monitoring of the disease was not optimal, response rates were similar to those reported in previous studies. It is clear to us that improvements should be made in treatment of AP-CML and high Sokal risk group of CP-CML. The frontline use of second-generation tyrosine kinase inhibitor (TKI) is expected to improve the results of the first-line treatment of these high-risk Tunisian patients, but cost and accessibility of this therapy remain the problems in developing countries.

Emotional Intelligence (EI) can be defined as an "ability to monitor one's own and others' feelings and emotions, to discriminate among them and to use this information to guide one's thinking and actions" (Salovey and Mayer, 1990) [1]. As such EI plays a major role in sport sciences. Studies conducted so far have shown contrasting findings. The paper contains data concerning the psychometric properties of the "Profile of Emotional Competence" questionnaire administered to a sample of 479 subjects (239 athletes, 240 non-athletes, age ranging from 12 to 18 years old, 239 men, and 240 women) in order: i) to explore EI between athletes and non-athletes students and ii) to examine differences in EI of young participants in terms of gender and age.

Cutaneous leishmaniosis (CL) is treated with pentavalent antimony (SbV) as a first-line drug, while amphotericin B and paromomycin are potential alternatives in antimonial- resistant isolates. However, the mechanisms of drug resistance remain unclear. The present study analyses the gene expression of RNA polymerase II (RNAP II) and J-binding protein 1 (JBP1), and J-binding protein 2 (JBP2) in Leishmania major after exposure to drugs in vitro. L. major (MRHO/IR/75/ER) promastigotes were exposed to various concentrations of glucantime, paromomycin and amphotericin B for 72 hours. The RNA was then extracted and used for cDNA synthesis. The expressions of JBP1, JBP2 and RNAP II were analysed using SYBR Green real-time PCR. No change in JBP2 or RNAP II expression was associated with amphotericin B, but JBP1 expression decreased with increasing drug concentration. Paromomycin had no effect on JBP2 expression, but a 13.5-fold increase in JBP1 was observed at 100 μg/ml, and a decrease in RNAP II expression at 25 and 50 μg/ml. Exposure to glucantime resulted in 1.4-fold lower JBP1 expression at 5 μg/ml, and 333.33- to 500-fold lower RNAP II at concentrations of 5 to 15 μg/ml. As Base J synthesis requires both JBP1 and JBP2, RNAP II (encoding RNA polymerase II) could reduce expression. However, RNAP II was not expressed in all groups, indicating that the genes associated with drug resistance may be regulated in other ways.

: Factor XIII deficiency is a rare autosomal recessive disorder of hemostasis characterized by a plasmatic factor XIII level less than 1% in homozygote and bleeding as of the youth. The aim of the study is to describe the clinical features and the outcome of the patients and to determine molecular characteristics. A retrospective study, was conducted on seven patients with factor XIII deficiency in the department of hematology and pediatrics, Hedi Chaker Hospital, Sfax, Tunisia during the period of 14 years (2001-2014). The activity of factor XIII in plasma of the patients was less than 1%. Seven patients from five unrelated families were recorded (four men and three women). Median age at diagnosis was 3.5 years. All patients had consanguineous parents. Six patients presented umbilical bleeding and only three patients had intracranial bleeding. Other bleeding features were seen, including skin and mucosal bleeding, muscular hematoma, and splenic rupture. Recurrent abortions were observed in one patient. The standard screening tests were normal. Genetic analysis identified two mutations interesting the subunit A of factor XIII. All patients received transfusion of fresh frozen plasma monthly. One patient was died because of intracranial hemorrhage.Factor XIII deficiency is a rare bleeding disorder which frequently increases in areas with high consanguinity. In our study, we identified a founder mutation. The prognosis of the disorder is related to hemorrhagic complications especially to life-threatening intracranial bleeding. Prophylaxis consists of factor XIII concentrate or recombinant factor XIII. If these are unavailable, fresh frozen plasma may be used.

The aim of the present study was to evaluate in patients with acute lymphoblastic leukemia (ALL), the oxidative status and antioxidant defense and its involvement in the relapse of ALL. The plasmatic levels of malondialdehyde, advanced oxidation of protein products and reduced glutathione (GSH), and the plasmatic activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase were determined in 34 patients who were newly diagnosed with ALL and compared with 92 healthy individuals. The plasmatic concentrations of malondialdehyde and advanced oxidation of protein products were higher in ALL patients than in controls and increased during chemotherapy. A decrease in glutathione peroxidase activity and an increase in catalase and SOD activities and GSH plasma levels were observed in ALL patients, as compared with sex-matched controls. Moreover, SOD activity and GSH levels were significantly correlated with the relapse of ALL patients. These data suggest the involvement of oxidative stress in acute lymphoid leukemias and leukemic relapse.