Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Frequency and clinical impact of CDKN2A/ARF/CDKN2B gene deletions as assessed by in-depth genetic analyses in adult T cell acute lymphoblastic leukemia.

Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL. Here, we investigated the presence of homozygous and heterozygous deletions of the CDKN2A/ARF and CDKN2B genes in 64 adult T-ALL patients enrolled in two consecutive trials from the Spanish PETHEMA group. Alterations in CDKN2A/ARF/CDKN2B were detected in 35/64 patients (55%). Most of them consisted of 9p21 losses involving homozygous deletions of the CDKNA/ARF gene (26/64), as confirmed by single nucleotide polymorphism (SNP) arrays and interphase fluorescence in situ hybridization (iFISH). Deletions involving the CDKN2A/ARF/CDKN2B locus correlated with a higher frequency of cortical T cell phenotype and a better clearance of minimal residual disease (MRD) after induction therapy. Moreover, the combination of an altered copy-number-value (CNV) involving the CDKN2A/ARF/CDKN2B gene locus and undetectable MRD (≤ 0.01%) values allowed the identification of a subset of T-ALL with better overall survival in the absence of hematopoietic stem cell transplantation.

Reuse of olive mill effluents from two-phase extraction process by integrated advanced oxidation and reverse osmosis treatment.

In this work, complete reclamation of the olive mill effluents coming from a two-phase olive oil extraction process (OME-2) was studied on a pilot scale. The developed depuration procedure integrates an advanced oxidation process based on Fenton's reagent (secondary treatment) coupled with a final reverse osmosis (RO) stage (purification step). The former aims for the removal of the major concentration of refractory organic pollutants present in OME-2, whereas the latter provides efficient purification of the high salinity. Complete physicochemical composition of OME-2 after the secondary treatment was examined, including the particle size distribution, organic matter gradation and bacterial growth, in order to assess the selection of the membrane and its fouling propensity. Hydrodynamics and selectivity of the membrane were accurately modelized. Upon optimization of the hydrodynamic conditions, the RO membrane showed stable performance and fouling problems were satisfactorily overcome. Steady-state permeate flux equal to 21.1 L h(-1)m(-2) and rejection values up to 99.1% and 98.1% of the organic pollutants and electroconductivity were respectively attained. This ensured parametric values below standard limits for reuse of the regenerated effluent, e.g. in the olives washing machines, offering the possibility of closing the loop and thus rending the production process environmentally friendly.

Effective treatment of olive mill effluents from two-phase and three-phase extraction processes by batch membranes in series operation upon threshold conditions.

Production of olive oil results in the generation of high amounts of heavy polluted effluents characterized by extremely variable contaminants degree, leading to sensible complexity in treatment. In this work, batch membrane processes in series comprising ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) are used to purify the effluents exiting both the two-phase and tree-phase extraction processes to a grade compatible to the discharge in municipal sewer systems in Spain and Italy. However, one main problem in applying this technology to wastewater management issues is given by membrane fouling. In the last years, the threshold flux theory was introduced as a key tool to understand fouling problems, and threshold flux measurement can give valuable information regarding optimal membrane process design and operation. In the present manuscript, mathematical approach of threshold flux conditions for membranes operation is addressed, also implementing proper pretreatment processes such as pH-T flocculation and UV/TiO2 photocatalysis with ferromagnetic-core nanoparticles in order to reduce membranes fouling. Both influence the organic matter content as well as the particle size distribution of the solutes surviving in the wastewater stream, leading, when properly applied, to reduced fouling, higher rejection and recovery values, thus enhancing the economic feasibility of the process.

Impacts of operating conditions on reverse osmosis performance of pretreated olive mill wastewater.

Management of the effluent from the olive oil industry is of capital importance nowadays, especially in the Mediterranean countries. Most of the scarce existing studies concerning olive mill wastewater (OMW) treatment by means of membrane processes not only do fix their aims simply on achieving irrigation standards, but lack suitable pretreatments against deleterious fouling issues. With the target of achieving the parametric requirements for public waterways discharge or even for reuse in the production process, a bench-scale study was undertaken to evaluate the feasibility of a thin-film composite reverse osmosis (RO) membrane (polyamide/polysulfone) for the purification of OMW. Previously, OMW was pretreated by means of chemical oxidation based on Fenton's reagent, flocculation-sedimentation and biosorption through olive stones. Impacts of the main operating parameters on permeate flux and pollutants rejection of the RO process, as well as fouling on the membrane surface, were examined for removing the significant ionic concentration and remaining organic matter load of the pretreated OMW. Combining operating parameters adequately in a semibatch operating regime ensured high and sustainable permeate flux, yielding over 99.4% and 98.5% removal efficiencies for the chemical oxygen demand and ionic content respectively, as well as complete rejection of phenols, iron and suspended solids.

Treatment of olive-mill wastewater from a two-phase process by chemical oxidation on an industrial scale.

This study offers a solution for reducing the environmental effect of wastewaters generated by the olive-oil industry. Olive-oil companies produce variable quantities of wastewaters, which require treatment for disposal or reuse. Today, regulations are becoming increasingly strict regarding the parameters measured in these effluents. In Spain, the resolution by the president of the Hydrographical Confederation of the Guadalquivir on water use 2004 set parameter limits as follows: pH = 6.0-9.0, total suspended solid = 500 mg/L; and COD and BOD(5) (20)=1,500 mg O(2)/L. For the year 2006, maximum values for COD and BOD(5) (20) were fixed at 1,000 mg O(2)/L. To solve this problem, a study has been made to derive irrigation water from the above-mentioned effluents through chemical oxidation based on the Fenton's process. This would be first step towards using a closed-circuit system in olive-oil mills to treat and reuse effluents.

CLUM: a cluster program for analyzing microarray data.

Microarray technology is increasingly being applied in biological and medical research to address a wide range of problems. Cluster analysis has proven to be a very useful tool for investigating the structure of microarray data. This paper presents a program for clustering microarray data, which is based on the so call path-distance. The algorithm gives in each step a partition in two clusters and no prior assumptions on the structure of clusters are required. It assigns each object (gene or sample) to only one cluster and gives the global optimum for the function that quantifies the adequacy of a given partition of the sample into k clusters. The program was tested on experimental data sets, showing the robustness of the algorithm.

[Historical review of the borderline personality disorder concept]. / Revisión histórica del concepto de trastorno limítrofe de la personalidad (borderline).

INTRODUCTION: The concept of borderline syndrome is the subject of current debate because of its ambiguity and lack of homogeneity. Furthermore, the concept is rejected by many authors as a common category for atypical and non-specific disorders that cannot be classified elsewhere. The current use of the term borderline seems to be more a consequence of its historic use than its true clinical meaning. There is discrepancy on whether this term determines a level of severity, an organization of personality or a defined syndromic entity. In 1938, Stern was the first author to use the term borderline, and it was not introduced in the DSM III until 1980. OBJECTIVE: This work makes a historical review of the use of the term borderline and also of those terms that have been used to define patients with the same characteristics. CONCLUSION: The different schools (psychoanalytic, biological, eclectic and biosocial) have different concepts on the term borderline. There is still no concise and exact definition for the diagnostic criteria of borderline and it is even possible the best term for this group of patients has still not been determined. It will be important to consider the contributions of the DSM V or ICD 11 in the next years.

An LD50 model for predicting psychotropic drug toxicity using biopartitioning micellar chromatography.

The LD50 determination is the main way to measure the acute toxicity of all types of substances. At the present time, however, there is increasing opposition to the use of living animals in research and testing activities from animal rights groups as well as some scientists. Nevertheless, the need to have a tool for estimating the potential toxicity of new compounds for human consumption has encouraged the development of alternative methods. Under adequate conditions, the partitioning in micellar liquid chromatography can describe the drug biopartitioning. We have named this chromatographic system biopartitioning micellar chromatography (BMC). In this paper, an LD50 QRAR model developed for psychotropic drugs from their retention data in BMC, is described. The model's ability to predict new psychotropic drug toxicity is statistically proved.

Survey and host fitness effects of red-cockaded woodpecker blood parasites and nest cavity arthropods.

Blood parasites and nest cavity arthropods associated with the red-cockaded woodpecker (Picoides borealis) were surveyed and the impact of blood-feeding arthropods on woodpecker fitness traits was assessed. Five woodpeckers (8%) were infected with unidentified microfilariae, and 1 woodpecker (2%) was infected with 2 species of haemoproteid (Haemoproteus velans and Haemoproteus borgesi). This is the first record of haemoproteids in this species and the first observation of H. borgesi in North America. We collected representatives of at least 6 families of mites and 12 families of primarily commensal insects from woodpecker cavities. Only a few specimens of blood-feeding insects were recovered. The mite Androlaelaps casalis was the most common hematophagous arthropod (prevalence = 76%, mean density = 51+/-7 mites/cavity). The number of A. casalis mites increased with cavity age but there was no association between the number of mites and the number of woodpecker eggs laid or the number of hatchlings or fledglings. In conclusion, the prevalence of blood parasites in the red-cockaded woodpecker is low, woodpecker cavities are not heavily infested with blood-feeding insects, and there is no evidence that A. casalis mites affect woodpecker fitness.

Genetic study of the population of Tenerife (Canary Islands, Spain): protein markers and review of classical polymorphisms.

Data on six protein polymorphisms (19 alleles) from the human population of Tenerife are presented and discussed along with other classical markers in relation to the origin of the Canarians. Genetic influences from three population groups were considered: the Iberians, and the Berbers and non-Berbers (Arabs) from north Africa. The systems examined show the Tenerife population lies within the limits of variation described for various Iberian groups, with a slight tendency towards the characteristics of north African populations. When blood groups, red cell enzymes and serum protein data were considered, the similarity of the Canary population to Iberians seems strengthened (70% estimated contribution of Iberian peninsula genes to the present-day Canarian pool), while some relation with north African groups is shown. Genetic distances between Canarians and Arabs and Canarians and Berbers are lower than those between the two north African groups, indicating a relative and comparable contribution of each to the present-day gene pool of the Canarian population. The Arab contribution could be attributable to the slaves who were introduced to these islands after the conquest in the 15th century, while the Berber contribution could be the remnants of the extinct aboriginal peoples of the islands (Guanches) or a more recent immigration due to slavery. Genetic data do not allow us to distinguish between these two possibilities.

Human genetic variation in the Sierra de Gredos mountain (central Spain): study of several polymorphisms.

The variation in the third component of human complement (C3) and orosomucoid (ORM1) serum proteins, and 6-phosphogluconate dehydrogenase (6PGD), adenosine deaminase (ADA), esterase D (ESD), and acid phosphatase (ACP1) red cell enzymes was examined in two samples from autochthonous populations living on either side of the Sierra de Gredos range in Central Spain. These results support only a moderate differentiation between Gredos subpopulations, which is discussed in relation to other Iberian Peninsula groups. Allele frequencies in Gredos show a remarkable heterogeneity as contrasted with other Iberian populations for most of the markers examined; relatively high C3*S, ORM1*F, ADA*1, ESD*2, and ACP1*C gene frequencies are characteristics of Gredos samples. This differentiation was more marked for the Northern Gredos population and could be related to the geographical peculiarities of this region.

[Self perception of health and complete evaluation of the elderly patient at a primary care center]. / Autopercepción de salud y evaluación integral del paciente anciano en un centro de atención primaria.

OBJECTIVES: 1) To make an integrated evaluation of the cognitive status, functional capacity, chronic disorders and social situation of the over-75 age group. 2) To find this group's self-perception of their health. DESIGN: A descriptive crossover study. SETTING: The Gòtic Health District in Barcelona. PARTICIPANTS: 316 people were included in the study. They were chosen by simple randomised sampling from the over-75s seen at the centre (n = 1,625). MEASUREMENTS AND MAIN RESULTS: To assess cognitive status, the Pfeiffer Short Portable Mental Status Questionnaire was used; for functional capacity, the Katz Index; and for chronic disorders, the medical records were reviewed. A questionnaire was used to find patients' social situation and assessed social relationships, social resources used and architectonic barriers. Self-perception of health status was evaluated using the Nottingham Health Profile. Prevalence of cognitive deterioration was 29.7%. 39.4% of patients were dependent in one or more basic activities of their daily life. 90.8% had a chronic disorder, the most frequent being AHT, arthrosis, obesity and dyslipemias. 28.3% lived alone and 26.7% used social services. CONCLUSIONS: We think this kind of assessment is useful in primary care. It would provide an integrated diagnosis (clinical, functional, medical and social) of elderly patients.

Serum protein polymorphisms (HP, TF-, GC- and PI subtypes) in two mountain communities of Sierra de Gredos (central Spain).

The genetic variation of four highly polymorphic serum proteins, haptoglobin (HP), transferrin (TF), group-specific component (GC) and alpha-1-antitrypsin (PI) was examined in two representative samples of the autochthonous populations living on either slope of Sierra de Gredos in central Spain. The genetic markers studied do not provide any evidence that the mountain chain has contributed to the maintenance of a genetic differentiation between the two populations. The allele frequency distributions in these Gredos samples are discussed in relation to the variability of these markers in the Iberian Peninsula populations.

Orosomucoid and haptoglobin polymorphisms in two Spanish Pyrenean populations.

Serum samples of autochthonous individuals from the Garrotxa prepyrenean region, and the Pallars Sobirà valley were screened for HP (Haptoglobin) and ORM (Orosomucoid) types by polyacrylamide isoelectric focusing and electrophoresis. The allele frequencies estimated were HP*1 = 0.3902 and ORM1*S = 0.3697 for Pallars Sobirà, and HP*1 = 0.4161 and ORMS1*S = 0.3691 in the Garrotxa. While our results for the HP system are within the range of variation of the Iberian Peninsula, the ORM1 protein shows a remarkable degree of variation among these populations.

Serum protein markers in the Piaroa Indians of Amazonia (Venezuela).

A sample of 121 Piaroa Indians from the Federal Amazonia Territory (Venezuela) was studied for the following serum protein polymorphisms: haptoglobin (HP), group-specific component subtypes (GC), orosomucoid (ORM), third component of complement (C3), transferrin C subtypes (TF) and alpha 1-antitrypsin subtypes (PI). The gene frequencies in the whole sample were: HP1 = 0.821; GC1S = 0.698; GC1F = 0.058; GC2 = 0.244; ORMS = 0.434; C3S = 0.699; C3F = 0.289; C3var = 0.012; TFC1 = 0.955; PIM1 = 0.467; PIM2 = 0.004; PIM3 = 0.529. The studied Piaroa sample came from three different communities: Gavilan, Paria and Alto Carinagua. The distribution of GC, C3 and HP polymorphisms was heterogeneous within the three groups. All the examined serum protein markers were polymorphic, in contrast to some enzymatic markers (ADA, DIA, 6PGD, AK) previously studied, which were shown to be monomorphic in the Piaroa. The results were compared with data from other populations living in the same territory.

Haptoglobin subtypes in two Spanish Pyrenean populations.

Haptoglobin subtypes have been determined in two population samples, one of them from the Pyrenean Valley of Pallars Sobirá in the province of Lérida and other from the Garrotxa region, province of Gerona. The obtained frequencies have been compared with other Pyrenean and European populations. Our results contrast with the absence of HP*2FF in the north-eastern district of the Pyrenees and suggest a more extensive distribution of this allele in European populations.

Device for data-acquisition from transient signals: kinetic considerations.

This paper reports on the evaluation and testing of a home-made device. Data-acquisition, treatment of transient signals and the hardware and software involved are discussed. Some practical aspects are developed in order to power the autonomy of procedures using the device. Kinetic and multi-signal calculations are considered in order to cover the actual tendencies in continuous-flow analysis. Somepractical advantages versus the use of classical chart recorders or commercial computerized-instrument devices are pointed out.

An oxidative column for the flow injection analysis-spectrophotometric determination of paracetamol.

A flow injection-spectrophotometric determination of paracetamol is reported. The procedure is based on the oxidation of the analyte with potassium hexacyanoferrate(III) previously retained in an anionic exchange column and the reaction of the N-(hydroxyphenyl)-p-benzoquinonimine so produced with phenol. The oxidation is carried out at room temperature and in aqueous ammoniacal solution. Concentrations of paracetamol in the 0.20-20 ppm range are determined with relative standard deviations (RSD) of 0.6% (n = 40) at an injection rate of 42 samples h-1. The influence of foreign species on the assay and its application to the determination of paracetamol in several pharmaceutical formulations are reported.