Remediation of soils contaminated with methomyl using electrochemically produced gaseous oxidants.

This prospective work focuses on the use of two different gaseous oxidants (chlorine dioxide and ozone) to remediate soil polluted with methomyl in two different applications: ex-situ and in-situ. In the first, the soil washing is integrated with the bubbling of the oxidant, while in the second, the gas was introduced by a perforated pipe located sub-superficially. Regarding the soil washing treatment, results demonstrate that direct use of ozone is not very efficient, although an important improvement is obtained following activation with hydrogen peroxide or UV light. In contrast, chlorine dioxide exhibited complete methomyl depletion from the soil, although with higher energy consumption and technical complexity compared to ozone. The direct dosing of the gaseous oxidants in perforated pipes is effective, achieving methomyl removals of 7.8 % and 9.2 % using ozone and chlorine dioxide, respectively. In these cases, soil conditions are not significantly modified, which becomes an important advantage of the technology as compared with other electrochemically assisted soil remediation process, in which large regions of the treated soil are affected by important changes in the pH or by depletion of ions. This lower impact makes these novel technologies more promising for further evaluations.

Treatment of Organics in Wastewater Using Electrogenerated Gaseous Oxidants.

This work focuses on the comparison of the performance of direct electrochemical oxidation with indirect electrolysis mediated by gaseous oxidants in the treatment of diluted wastewater. To do this, energy consumptions of the electrolysis using mixed metal oxide (MMO) electrodes are compared with those required for the production and use of chlorine dioxide in the degradation of methomyl contained in aqueous solutions. Results demonstrate the feasibility of the mediated oxidation process and that this process is competitive with direct oxidation. The oxidants are produced under optimized conditions using the same anodic material applied for the direct degradation of organics, thus avoiding efficiency losses associated with mass transfer limitations in the degradation of dilute organic solutions. Thus, using the ClO2 gaseous oxidant, a concentration of 0.1 mM of methomyl from a solution containing 500 mL is completely removed with an energy consumption as low as 50 Wh. The application of the same energy to a direct electrolytic process for treating the same wastewater can only reach less than half of this removal. These findings may have a very important application in the use of electrochemical technology to achieve the remediation of persistent pollutants in wastewater, where their low concentrations typically make direct processes very inefficient.

From field-induced to zero-field SMMs associated with open/closed structures of bis(ZnDy) tetranuclear complexes: a combined magnetic, theoretical and optical study.

We have prepared a bis(compartmental) Mannich base ligand H4L (1,4,8,11-tetraaza-1,4,8,11-tetrakis(2-hydroxy-3-methoxy-5-methylbenzyl)cyclotetradecane) specifically designed to obtain bis(TMIILnIII) tetranuclear complexes (TM = transition metal). In this regard, we have succeeded in obtaining three new complexes of the formula [Zn2(µ-L)(µ-OAc)Dy2(NO3)2]·[Zn2(µ-L)(µ-OAc)Dy2(NO3)(OAc)]·4CHCl3·2MeOH (1) and [TM2(µ-H2L)2(µ-succinate)Ln2(NO3)2] (NO3)2·2H2O·6MeOH (TMII = Zn, LnIII = Dy (2); TMII = Co, LnIII = Dy (3)). Compound 1 contains two different bis(ZnDy) tetranuclear molecules that cocrystallize in the structure, in which acetato bridging ligands connect the ZnII and DyIII ions within each ZnDy subunit. This compound does not exhibit slow magnetic relaxation at zero field, but it is activated in the presence of an applied dc magnetic field and/or by Dy/Y magnetic dilution, showing two relaxation processes corresponding to each of the two different bis(ZnDy) units found in the structure. As revealed by the theoretical calculations, magnetic relaxation in 1 is single-ion in origin and takes place through the first excited state of each DyIII ion. When using the succinato dicarboxylate bridging ligand instead of acetate, compounds 2 and 3 were serendipitously formed, which have a closed structure with the succinate anion bridging two ZnDy subunits belonging to two different ligands. It should be noted that only compound 2 exhibits slow relaxation of magnetization in the absence of an external magnetic field. According to experimental and theoretical data, 2 relaxes through the second excited Kramers doublet (Ueff = 342 K). In contrast, 3 displays field-induced SMM behaviour (Ueff = 203 K). However, the Co/Zn diluted version of this compound 3Zn shows slow relaxation at zero field (Ueff = 347 K). Ab initio theoretical calculations clearly show that the weak ferromagnetic coupling between CoII and DyIII ions is at the origin of the lack of slow relaxation of this compound at zero field. Compound 2 and its diluted analogues 2Y and 3Zn show hysteresis loops at very low temperature, thus confirming their SMM behaviour. Finally, compounds 1 and 2 show DyIII based emission even at room temperature that, in the case of 2, allows us to extract the splitting of the ground 6H15/2 term, which matches reasonably well with theoretical calculations.

Multiple mask and boundary scoring R-CNN with cGAN data augmentation for bladder tumor segmentation in WLC videos.

Automatic diagnosis systems capable of handling multiple pathologies are essential in clinical practice. This study focuses on enhancing precise lesion localization, classification and delineation in transurethral resection of bladder tumor (TURBT) to reduce cancer recurrence. Despite deep learning models success, medical applications face challenges like small and limited datasets and poor image characterization, including the absence lack of color/texture modeling. To address these issues, three solutions are proposed: (1) an improved texture-constrained version of the pix2pixHD cGAN for data augmentation, addressing the tradeoff of generating high-quality images with enough stochasticity using the Fréchet Inception Distance (FID) measure. (2) Introducing the Multiple Mask and Boundary Scoring R-CNN (MM&BS R-CNN), a new mask sub-net scheme where multiple masks are generated from the different levels of the mask sub-net pipeline, improving segmentation accuracy by including a new scoring module to refine object boundaries. (3) A novel accelerated training strategy based on the SGD optimizer with the second momentum. Experimental results show significant mAP improvements: the data generation scheme improves by more than 12 %; MM&BS R-CNN proposed architecture is responsible for an improvement of about 1.25 %, and the training algorithm based on the second-order momentum increases mAP by 2-3 %. The simultaneous use of all three proposals improved the state-of-the-art mAP by 17.44 %.

Zero-Field SMM Behavior Triggered by Magnetic Exchange Interactions and a Collinear Arrangement of Local Anisotropy Axes in a Linear Co3II Complex.

A new linear trinuclear Co(II)3 complex with a formula of [{Co(µ-L)}2Co] has been prepared by self-assembly of Co(II) ions and the N3O3-tripodal Schiff base ligand H3L, which is obtained from the condensation of 1,1,1-tris(aminomethyl)ethane and salicylaldehyde. Single X-ray diffraction shows that this compound is centrosymmetric with triple-phenolate bridging groups connecting neighboring Co(II) ions, leading to a paddle-wheel-like structure with a pseudo-C3 axis lying in the Co-Co-Co direction. The Co(II) ions at both ends of the Co(II)3 molecule exhibit distorted trigonal prismatic CoN3O3 geometry, whereas the Co(II) at the middle presents an elongated trigonal antiprismatic CoO6 geometry. The combined analysis of the magnetic data and theoretical calculations reveal strong easy-axis magnetic anisotropy for both types of Co(II) ions (|D| values higher than 115 cm-1) with the local anisotropic axes lying on the pseudo-C3 axis of the molecule. The magnetic exchange interaction between the middle and ends Co(II) ions, extracted by using either a Hamiltonian accounting for the isotropic magnetic coupling and ZFS or the Lines' model, was found to be medium to strong and antiferromagnetic in nature, whereas the interaction between the external Co(II) ions is weak antiferromagnetic. Interestingly, the compound exhibits slow relaxation of magnetization and open hysteresis at zero field and therefore SMM behavior. The significant magnetic exchange coupling found for [{Co(µ-L)}2Co] is mainly responsible for the quenching of QTM, which combined with the easy-axis local anisotropy of the CoII ions and the collinearity of their local anisotropy axes with the pseudo-C3 axis favors the observation of SMM behavior at zero field.

Germination test for the evaluation of plant-growth promoting microorganisms.

There is an increased interest for finding strains able to contribute to plant nutrition and health, since these are desirable for the formulation of agricultural bioinoculants. Obtaining a safe and efficient product requires exhaustive evaluations from which most methods used for this purpose involve the use of substrates or are established under uncontrolled conditions, so that various factors can mask the results of the plant-microorganism interaction. In vitro methods mostly involve the use of Petri Dishes (PD) but limit the results to seed germination. Other methods of germination involve the use of acrylic boxes (GB) allowing for better plant development, but are little known. Methods such as ISTA are widely used to evaluate the physiological quality of seeds in productive terms. Despite their efficiency, these methods have not been previously used to evaluate the effect of plant-microorganism interaction on crops. In the present study, modifications were made to the germination between paper of ISTA (BP) method, and were compared to the PD anf GB methods to evaluate the impact of the bacterium Serratia liquefaciens 385 and the yeast Clavispora lusitaniae Y35 on maize, bean and squash. Through the evaluation of physiological parameters in seed and seedling, the results clearly showed the superiority of the BP method to evaluate the effect of microorganisms since it allows observing a better development in the seedlings in terms of growth of the plumule, a better architecture of the radical system in which the emergence of adventitious secondary roots and differentiated radical hairs is observed in comparison with seedlings obtained under the other methods. Similarly, it was possible to observe the different effects on each of the three crops with respect to the inoculation of the bacteria and yeast. These results were significantly better in seedlings obtained in the BP method independently of the type of crop evaluated, considering the BP method suitable to be applied in large-scale bioprospecting plant-growth-promoting microorganism studies.

Dexametasona frente a metilprednisolona ajustada al peso en pacientes con neumonía moderada-grave por SARS-CoV-2 / Dexamethasone versus weight-adjusted methylprednisolone in patients with moderate-severe SARS-CoV-2 pneumonia

Objetivos: Comparar el desenlace clínico (mortalidad y/o ingreso en UCI) a 30 días de los pacientes ingresados por neumonía moderada-grave por SARS-CoV-2 tratados con dexametasona tras el estudio RECOVERY frente aquellos tratados con metilprednisolona ajustada al peso.MétodosEstudio de cohortes retrospectivo de 65 pacientes con neumonía moderada-grave que recibieron 6 mg/día de dexametasona (grupo DXM) frente a 80 tratados con metilprednisolona ajustada al peso (grupo MTPN).ResultadosFallecieron 21 (32,3%) pacientes del grupo DXM vs. 8 (10%) del grupo MTPN (valor p < 0,001) y 29 (44,6%) del grupo DXM requirieron ingreso en UCI vs. 2 (2,5%) del grupo MTPN (valor p < 0,001). No hubo diferencias basales respecto a características sociodemográficas con un qSOFA medio superior en el grupo MTPN. La razón de riesgo para la mortalidad y el ingreso en UCI ajustada por edad, sexo y PCR al ingreso fue de 2,189 (1,082-4,426; IC 95%) y 10,589 (2,139-48,347; IC 95%) para el grupo DXM, respectivamente, vs. grupo MTPN.ConclusionesLa mortalidad e ingreso en UCI fue menor en pacientes tratados con metilprednisolona ajustada al peso frente a los tratados con dexametasona. (AU)

Objectives: To compare the 30-day outcome (mortality and/or ICU admission) of patients admitted for moderate-severe SARS-CoV-2 pneumonia treated with dexamethasone after the Recovery study versus those treated with weight-adjusted methylprednisolone.MethodsRetrospective cohort study of 65 patients with moderate-severe pneumonia who received dexamethasone 6 mg/day (DXM group) versus 80 treated with weight-adjusted methylprednisolone (MTPN group).ResultsTwenty-one (32.3%) patients in the DXM group died vs. 8 (10%) in the MTPN group (p-value < 0.001) and 29 (44.6%) in the DXM group required ICU admission vs. 2 (2.5%) of the MTPN group (p-value < 0.001). There were no baseline differences regarding sociodemographic characteristics with a higher mean qSOFA in the MTPN group. The hazard ratio for mortality and ICU admission adjusted for age, sex, and admission CRP was 2.189 (1.082–4.426; 95% CI) and 10.589 (2.139–48.347; 95% CI) for the DXM group, respectively, vs. MTPN group.ConclusionsMortality and admission to the ICU were lower in patients treated with weight-adjusted methylprednisolone compared to those treated with dexamethasone. (AU)

Pushing up the easy-axis magnetic anisotropy and relaxation times in trigonal prismatic CoII mononuclear SMMs by molecular structure design.

The replacement of pyridine by 1-methyl-imidazol in the arms of a N6-tripodal ligand allows preparing two new CoII complexes with quasi-ideal triangular prismatic geometry, which behave as SIMs (Single Ion Magnets) at zero dc field with enhanced axial magnetic anisotropy, magnetic relaxation times and magnetic hysteresis.

Dexamethasone versus weight-adjusted methylprednisolone in patients with moderate-severe SARS-CoV-2 pneumonia.

Objectives: To compare the 30-day outcome (mortality and/or ICU admission) of patients admitted for moderate-severe SARS-CoV-2 pneumonia treated with dexamethasone after the Recovery study versus those treated with weight-adjusted methylprednisolone. Methods: Retrospective cohort study of 65 patients with moderate-severe pneumonia who received dexamethasone 6 mg/day (DXM group) versus 80 treated with weight-adjusted methylprednisolone (MTPN group). Results: 21 (32.3%) patients in the DXM group died vs 8 (10%) in the MTPN group (p-value < 0.001) and 29 (44.6%) in the DXM group required ICU admission vs 2 (2,5%) of the MTPN group (p-value <0.001). There were no baseline differences regarding sociodemographic characteristics with a higher mean qSOFA in the MTPN group. The hazard ratio for mortality and ICU admission adjusted for age, sex, and admission CRP was 2.189 (1.082-4.426; 95% CI) and 10.589 (2.139-48.347; 95% CI) for the DXM group, respectively, vs. MTPN group. Conclusions: Mortality and admission to the ICU were lower in patients treated with weight-adjusted methylprednisolone compared to those treated with dexamethasone.

Objetivos: Comparar el desenlace clínico (mortalidad y/o ingreso en UCI) a 30 días de los pacientes ingresados por neumonía moderada-grave por SARS-CoV-2 tratados con dexametasona tras el estudio Recovery frente aquellos tratados con metilprednisolona ajustada al peso. Métodos: Estudio de cohortes retrospectivo de 65 pacientes con neumonía moderada-grave que recibieron 6 mg/día de dexametasona (grupo DXM) frente a 80 tratados con metilprednisolona ajustada al peso (grupo MTPN). Resultados: Fallecieron 21 (32,3%) pacientes del grupo DXM vs 8 (10%) del grupo MTPN (p-valor < 0,001) y 29 (44,6%) del grupo DXM requirieron ingreso en UCI vs 2 (2,5%) del grupo MTPN (p-valor < 0,001). No hubo diferencias basales respecto a características sociodemográficas con un qSOFA medio superior en el grupo MTPN. La razón de riesgo para la mortalidad y el ingreso en UCI ajustada por edad, sexo y PCR al ingreso fue de 2,189 (1,082−4,426; IC 95%) y 10,589 (2,139−48,347; IC 95%) para el grupo DXM, respectivamente, vs grupo MTPN. Conclusiones: La mortalidad e ingreso en UCI fue menor en pacientes tratados con metilprednisolona ajustada al peso frente a los tratados con dexametasona.

[Dexamethasone versus weight-adjusted methylprednisolone in patients with moderate-severe SARS-CoV-2 pneumonia]. / Dexametasona frente a metilprednisolona ajustada al peso en pacientes con neumonía moderada-grave por SARS-CoV-2.

OBJECTIVES: To compare the 30-day outcome (mortality and/or ICU admission) of patients admitted for moderate-severe SARS-CoV-2 pneumonia treated with dexamethasone after the Recovery study versus those treated with weight-adjusted methylprednisolone. METHODS: Retrospective cohort study of 65 patients with moderate-severe pneumonia who received dexamethasone 6 mg/day (DXM group) versus 80 treated with weight-adjusted methylprednisolone (MTPN group). RESULTS: Twenty-one (32.3%) patients in the DXM group died vs. 8 (10%) in the MTPN group (p-value < 0.001) and 29 (44.6%) in the DXM group required ICU admission vs. 2 (2.5%) of the MTPN group (p-value < 0.001). There were no baseline differences regarding sociodemographic characteristics with a higher mean qSOFA in the MTPN group. The hazard ratio for mortality and ICU admission adjusted for age, sex, and admission CRP was 2.189 (1.082-4.426; 95% CI) and 10.589 (2.139-48.347; 95% CI) for the DXM group, respectively, vs. MTPN group. CONCLUSIONS: Mortality and admission to the ICU were lower in patients treated with weight-adjusted methylprednisolone compared to those treated with dexamethasone.

Development of a New Integrated System for Vital Sign Monitoring in Small Animals.

Monitoring the vital signs of mice is an essential practice during imaging procedures to avoid populational losses and improve image quality. For this purpose, a system based on a set of devices (piezoelectric sensor, optical module and thermistor) able to detect the heart rate, respiratory rate, body temperature and arterial blood oxygen saturation (SpO2) in mice anesthetized with sevoflurane was implemented. Results were validated by comparison with the reported literature on similar anesthetics. A new non-invasive electrocardiogram (ECG) module was developed, and its first results reflect the viability of its integration in the system. The sensors were strategically positioned on mice, and the signals were acquired through a custom-made printed circuit board during imaging procedures with a micro-PET (Positron Emission Tomography). For sevoflurane concentration of 1.5%, the average values obtained were: 388 bpm (beats/minute), 124 rpm (respirations/minute) and 88.9% for the heart rate, respiratory rate and SpO2, respectively. From the ECG information, the value obtained for the heart rate was around 352 bpm for injectable anesthesia. The results compare favorably to the ones established in the literature, proving the reliability of the proposed system. The ECG measurements show its potential for mice heart monitoring during imaging acquisitions and thus for integration into the developed system.

Brain-Derived Neurotrophic Factor and Psychophysiological Response in Youth Badminton Athletes During the Season.

PURPOSE: To analyze peripheral brain-derived neurotrophic factor (BDNF) levels and psychophysiological parameters in youth badminton athletes during the season and to determine the relationship between variables. METHODS: Fourteen young badminton athletes were assessed over the season (preseason, middle season, and final season). Serum BDNF (sBDNF) was determined during the preseason and final season. Sleep time, total physical activity, and time in vigorous activity were measured using an accelerometer. The fat-free mass, skeletal muscle mass, fat mass, handgrip strength, cardiorespiratory fitness (VO2max), and dietary intake were evaluated during the season. The Stroop Color and Word Test was employed to assess cognitive tasks. To evaluate the mood, the Brunel Mood Scale was used. RESULTS: There  were lower sBDNF levels (-16.3% [46.8%]; P = .007) and sleep time (final season = 5.7 [1.1] vs preseason = 6.6 [1.1] h·night-1, P = .043) during the end of the season. The total calories and carbohydrate intake decreased across the season (P < .05). Conversely, better cognitive function was found in the final season with respect to the preseason (P < .05). There were significant correlations between BDNF and VO2max only in the preseason (r = .61, P = .027), but no significant relationship was found among sBDNF and cognitive performance, sleep time, and percentage of won games. CONCLUSIONS: Youth badminton athletes decreased their sBDNF levels, sleep time, carbohydrate, and calorie intake across the season. The athletes improved in cognitive function; however, only the females improved in body composition, and the males improved their VO2max in the middle season. The sBDNF levels were positively correlated with the VO2max in the preseason, and no correlations were observed among the sBDNF and psychological parameters, sleep time, and sport performance during the season.

Antiproliferative activity on Trypanosoma cruzi (Y strain) of the triterpene 3ß,6ß,16ß-trihidroxilup-20 (29)-ene isolated from Combretum leprosum.

Chagas disease infects approximately seven million people worldwide. Benznidazole is effective only in the acute phase of the disease, with an average cure rate of 80% between acute and recent cases. Therefore, there is an urgent need to find new bioactive substances that can be effective against parasites without causing so many complications to the host. In this study, the triterpene 3ß-6ß-16ß-trihydroxilup-20 (29)-ene (CLF-1) was isolated from Combretum leprosum, and its molecular structure was determined by NMR and infrared spectroscopy. The CLF-1 was also evaluated in vitro and in silico as potential trypanocidal agent against epimastigote and trypomastigote forms of Trypanosoma cruzi (Y strain). The CLF-1 demonstrated good results highlighted by lower IC50 (76.0 ± 8.72 µM, 75.1 ± 11.0 µM, and 70.3 ± 45.4 µM) for epimastigotes at 24, 48 and 72 h, and LC50 (71.6 ± 11.6 µM) for trypomastigotes forms. The molecular docking study shows that the CLF-1 was able to interact with important TcGAPDH residues, suggesting that this natural compound may preferentially exert its effect by compromising the glycolytic pathway in T. cruzi. The ADMET study together with the MTT results indicated that the CLF-1 is well-absorbed in the intestine and has low toxicity. Thus, this work adds new evidence that CLF-1 can potentially be used as a candidate for the development of new options for the treatment of Chagas disease.Communicated by Ramaswamy H. Sarma.

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.

Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype.

OBJECTIVE: Activating mutations of the fms-like tyrosine kinase 3 gene (FLT3) by internal tandem duplications (ITDs) in the juxtamembrane domain (JMD) have been reported in ~30% of adult acute myeloid leukemia (AML) patients with cytogenetically normal karyotype (CN). However, FLT3/ITD mutations are frequently accompanied with leukocytosis, high percentage of blasts in bone marrow (BM), and increased the risk of treatment failure in AML patients. FLT3-ITD mutated AML patients mainly with normal karyotype have higher relapse probability and shorter duration of complete remission (CR) after chemotherapy, so FLT3-ITD mutation is considered as an independent poor prognostic factor in AML. METHODS: FLT3-ITD and FLT3-KTD were studied by polymerase chain reaction (PCR) and restriction fragment length polymorphism- PCR (RFLP-PCR) in 44 adults AML patients with cytogenetically normal karyotype (AML-CN) at diagnosis to characterize FLT3 status. The results were correlated with the prognostic factors. RESULTS: In this study, FLT3-ITD mutations were identified in 7 (15.9%) of the 44 AML-CN patients. Among the 7 patients with FLT3/ITD mutations, 6 patients revealed a typical ITDs mutation (fragment size was 329 bp) and one patient showed untypical ITD mutation (fragment size was ~400 bp). Whereas 37 patients (61.7%) were FLT3-ITD. None of all AML-CN patients examined showed FLT3-KTD mutations. CONCLUSIONS: Our results support that FLT3-ITD are independent adverse prognostic factors for elderly AML-CN patients and are associated with low overall survival (OS), low rate of CR, high relapse rate (RR), and high percentage of BM blast at diagnosis. We concluded, FLT3 mutation analysis should be performed as a routine test in AML-CN patients.

Two Novel Mutations of the NPM1 Gene in Syrian Adult Patients with Acute Myeloid Leukemia and Normal Karyotype.

OBJECTIVE: Somatic mutations in exon 12 of the NPM1 gene is one of the most common genetic abnormalities in adult acute myeloid leukemia (AML), which is observed in 25-35% of AML patients and in 50-60% of patients with cytogenetically normal AML (CN-AML). METHODS: We performed Sanger sequencing of exon 12 of the NPM1 gene, on 44 CN-AML patients to characterize NPM1 status. RESULTS: In this study, NPM1 mutations were identified in 10 (22.7%) of the 44 CN-AML patients. Among the 10 patients with NPM1 mutations, type A NPM1 mutations were identified in 8 (80%) patients, whereas non-A type NPM1 mutations were observed in 2 (20%) patients. Two non-A type NPM1 mutations were not previously reported: c.867-868InsCGGA and c.861-862InsTGCA. These two novel mutant proteins display a nuclear export signal (NES) motif (L-xxx-L-xx-V-x-L) less frequently and L-x-Lx-V-xx-V-x-L it has been never seen before, yet. However, both novel mutations show a tryptophan loss at codon 288 and 290 at the mutant C-terminus which are crucial for aberrant nuclear export of NPM into the cytoplasm. CONCLUSIONS: This study suggests previously unreported NPM1 mutations may be non-rare and thus additional sequence analysis is needed along with conventional targeted mutational analysis to detect non type-A NPM1 mutations.

De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report.

BACKGROUND: Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet. CASE PRESENTATION: Here we report a 54-year-old Arab male diagnosed with AML who had two FLT3-ITD mutations in addition to NPM1 mutation. Cytogenetic approaches (banding cytogenetics) and fluorescence in situ hybridization (FISH) using specific probes to detect translocations t(8;21), t(15;17), t(16;16), t(12;21), and deletion del(13q)) were applied to exclude chromosomal abnormalities. Molecular genetic approaches (polymerase chain reaction (PCR) and the Sanger sequencing) identified a yet unreported combination of two new mutations in FLT3-ITDs. The first mutation induced a frameshift in JMD, and the second led to a homozygous substitution of c.1836T>A (p.F612L) also in JMD. Additionally a NPM1 type A mutation was detected. The first chemotherapeutic treatment was successful, but 1 month after the initial diagnosis, the patient experienced a relapse and unfortunately died. CONCLUSIONS: To the best of our knowledge, a combination of two FLT3-ITD mutations in JMD together with an NPM1 type A mutation were not previously reported in adult AML. Further studies are necessary to prove or rule out whether the size of these FLT3-ITDs mutations and potential other double mutations in FLT3-ITD are correlated with the observed adverse outcome.