Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus.

OBJECTIVE: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. RESULTS: Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. CONCLUSION: Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

Metabolomic analysis of heat-hardening in adult green-lipped mussel (Perna canaliculus): A key role for succinic acid and the GABAergic synapse pathway.

We evaluated the thermotolerance (LT50) of adult green-lipped mussels (Perna canaliculus) following an acute thermal challenge in the summer of 2012 and the winter of 2013. Mussels were grouped into two treatments, naïve (N, no prior heat treatment) and heat-hardened (HH = 1 h at 29 °C, 12 h recovery at ambient) before being immersed for 3 h in water of varying temperature, i.e. Ambient (Control), 25, 29, 31, 33, and 35 °C with subsequent mortality monitored for 30 days. As expected, naïve mussels were less thermotolerant than heat-hardened i.e. Summer LT50, N = 31.9, HH = 33.5 °C; Winter LT50, N = 31.4, HH = 33.8 °C. Moreover, at 33 °C no heat-hardened mussels died compared to 100% mortality in naïve specimens. At 35 °C all mussels died regardless of treatment. For the 'Summer' mussels, metabolite abundances in gill tissues of both naïve and heat-hardened mussels were quantified. For mussels at 33 °C, succinic acid was significantly higher in naïve mussels than heat-hardened mussels, indicating perturbations to mitochondrial pathways in these thermally stressed mussels. Additionally, analysis of biochemical pathway activity suggested a loss of neural control i.e. significantly reduced GABAergic synapse activity, in naïve vs. heat-hardened mussels at 33 °C. Taken together these findings suggest that heat-hardening improves mussel survival at higher temperatures by delaying the onset of cellular anaerobic metabolism, and by maintaining inhibition of neural pathways. Such results offer new perspectives on the complex suite of sub-cellular stress responses operating within thermally stressed organisms.

Possible involvement of orphan receptors GPR88 and GPR124 in the development of hypertension in spontaneously hypertensive rat.

Hypertension (HBP) is a chronic disease characterized by increased blood pressure, which despite several treatments maintains a high morbi-mortality, which suggests that there are other mechanisms involved in this pathology, within which the orphan receptors could be candidates for the treatment of the HBP; these receptors are called orphan receptors because their ligand is unknown. These receptors have been suggested to participate in some pathologies because they are associated with various systems such as GPR88, which has been linked to the dopaminergic system, and GPR124 with angiogenesis, suggesting that these receptors could take part in HBP. Hence, the aim of this work was to study the expression of orphan receptors GPR88 and GPR124 in various tissues of normotensive and hypertensive rats. We used Wistar Kyoto (WKY) and spontaneously hypertensive rat (SHR) of 6-8 and 10-12 weeks of age and we determined systolic blood pressure (SBP), heart rate, as well as mRNA of GPR88 and GPR124 receptors by reverse transcription polymerase chain reaction (RT-PCR) in the aorta, heart, kidney, and brain. Our results showed that GPR88 and GPR124 were expressed in all analyzed tissues, but their expression is dependent on the age and development of HBP because their expression tends to be modified as HBP is established. Therefore, we conclude that GPR88 and GPR124 receptors may be involved in the development or maintenance of high blood pressure.

An insight into the antibiofilm properties of Costa Rican stingless bee honeys.

OBJECTIVE: There is an increasing search for antibiofilm agents that either have specific activity against biofilms or may act in synergy with antimicrobials. Our objective is to examine the the antibiofilm properties of stingless bee honeys. METHOD: Meliponini honeys from Costa Rica were examined along with Medihoney as a reference. All honeys were submitted to a screening composed of minimum inhibitory concentration, inhibition of biofilm formation and biofilm destruction microplate-based assays against a Staphylococcus aureus biofilm forming strain. Dialysis led to the isolation of an antibiofilm fraction in Tetragonisca angustula honeys. The honey antibiofilm fraction was evaluated for protease activity and for any synergistic effect with antibiotics on a Staphylococcus aureus biofilm. The active fraction was then separated through activity guided isolation techniques involving SDS-PAGEs, anion exchange and size exclusion fast protein liquid chromatographies. The fractions obtained and the isolated antibiofilm constituents were tested for amylase and DNase activity. RESULTS: A total of 57 Meliponini honeys from Costa Rica were studied in this research. The honeys studied belonged to the Tetragonisca angustula (n=36) and Melipona beecheii (n=21) species. Costa Rican Tetragonisca angustula honeys can inhibit the planktonic growth, biofilm formation, and are capable of destroying a Staphylococcus aureus biofilm. The antibiofilm effect was observed in the protein fraction of Tetragonisca angustula honeys. The biofilm destruction proteins allowed ampicillin and vancomycin to recover their antimicrobial activity over a Staphylococcus aureus biofilm. The antibiofilm proteins are of bee origin, and their activity was not due to serine, cysteine or metalloproteases. There were 2 proteins causing the antibiofilm action; these were named the Tetragonisca angustula biofilm destruction factors (TABDFs). TABDF-1 is a monomeric protein of approximately 50kDa that is responsible of the amylase activity of Tetragonisca angustula honeys. TABDF-2 is a protein monomer of approximately 75kDa. CONCLUSION: Tetragonisca angustula honeys from Costa Rica are a promising candidate for research and development of novel wound dressings focused on the treatment of acute and chronic Staphylococcus aureus biofilm wound infections.

Safe Reduction in CD4 Cell Count Monitoring in Stable, Virally Suppressed Patients With HIV Infection or HIV/Hepatitis C Virus Coinfection.

BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.

Streptococcus cuniculi sp. nov., isolated from the respiratory tract of wild rabbits.

Biochemical and molecular genetic studies were performed on four unknown Gram-stain-positive, catalase-negative, coccus-shaped organisms isolated from tonsils (n = 3) and nasal samples (n = 1) of four wild rabbits. The micro-organism was identified as a streptococcal species based on its cellular morphological and biochemical tests. Comparative 16S rRNA gene sequencing confirmed its identification as a member of the genus Streptococcus, but the organism did not correspond to any recognized species of this genus. The closest phylogenetic relative of the unknown cocci from wild rabbits was Streptococcus acidominimus NCIMB 702025(T) (97.9% 16S rRNA gene sequence similarity). rpoB and sodA sequence analysis of the novel isolate showed interspecies divergence of 16.2% and 20.3%, respectively, from the type strain of its closest 16S rRNA gene phylogenetic relative, S. acidominimus. The novel bacterial isolate could be distinguished from the type strain of S. acidominimus by several biochemical characteristics, such as the production of esterase C4, acid phosphatase and naphthol-AS-BI-phosphohydrolase and acidification of different sugars. Based on both phenotypic and phylogenetic findings, it is proposed that the unknown bacterium be classified as a novel species of the genus Streptococcus, Streptococcus cuniculi sp. nov. The type strain is NED12-00049-6B(T) ( = CECT 8498(T) = CCUG 65085(T)).

Flavobacterium tructae sp. nov. and Flavobacterium piscis sp. nov., isolated from farmed rainbow trout (Oncorhynchus mykiss).

Four Gram-staining-negative, catalase- and oxidase-positive, pale-orange pigmented bacterial strains (435-08(T), 47B-3-09, 412R-09(T) and 60B-3-09) were isolated from diseased rainbow trout. Analysis of their 16S rRNA gene sequences suggested their adscription to the genus Flavobacterium. Strains formed two phylogenetic groups represented by strains 435-08(T) and 47B-3-09 (group A), and strains 412R-09(T) and 60B-3-09 (group B) displaying 16S rRNA sequence similarities greater than 99.8-99.9% within their respective groups. Strain 435-08(T) exhibited the highest levels of similarity with Flavobacterium aquidurense WB-1.1.56(T) (98.6% sequence similarity) and strain 412R-09(T) with Flavobacterium frigidimaris KUC-1(T) and Flavobacterium aquidurense WB-1.1.56(T) (98.9% and 98.6% sequence similarity, respectively). DNA-DNA hybridization studies showed low levels of relatedness between strain 435-08(T) and strain 412R-09(T) and between both strains and the most closely related species of the genus Flavobacterium. The genomic DNA G+C contents of strains 435-08(T) and 412R-09(T) were 36.2 and 34.3 mol%, respectively. The predominant respiratory quinone of both strains was MK-6 and the major fatty acids were iso-C(15 : 0), C(16 : 1)ω7c and C(15 : 0). The two groups of strains could be distinguished from each other and from related species of the genus Flavobacterium by a number of phenotypic properties. Phylogenetic, genotypic and phenotypic evidence indicated that strains of groups A and B represent two novel species of the genus Flavobacterium, for which the names Flavobacterium tructae sp. nov. (type strain 435-08(T) = CECT 7791(T) = CCUG 60100(T)) and Flavobacterium piscis sp. nov. (type strain 412R-09(T) = CECT 7911(T) = CCUG 60099(T)) are proposed.

Perceived exertion, time of immersion and physiological correlates in synchronized swimming.

This study examined the relationship between ratings of perceived exertion (RPE, CR-10), heart rate (HR), peak blood lactate (La peak), and immersion (IM) parameters in 17 elite synchronized swimmers performing 30 solo and duet routines during competition. All were video recorded (50 Hz) and an observational instrument was used to time the IM phases. Differences in the measured variables were tested using a linear mixed-effects model. RPE was 7.7 ± 1.1 and did not differ among routines, and neither did any of the HR parameters. There were differences among routines in La peak (F3,7=16.5; P=0.002), number of IM (F3,15=14.0; P<0.001), total time immersed (F3,16=26.6; P<0.001), percentage of time immersed (F3,13=6.5; P=0.007) and number of IM longer than 10 s (F3,19=3.0; P=0.04). RPE correlated positively to HR pre-activation, range of variation and recovery, IM parameters and La peak, and inversely to minimum and mean HR. A hierarchical multiple linear regression (MLR) model (number of IM >10 s, HR recovery, minimum HR, and La peak) explained 62% RPE variance (adj. Rm 2=0.62; P<0.001). A stepwise MLR model (La peak, mean IM time and pre-exercise HR) explained 46% of performance variance (adj. Rm 2=0.46; P<0.001). Findings highlight the psycho-physical stress imposed by the combination of intense dynamic exercise with repeated and prolonged apnea intervals during SS events.

Chryseobacterium viscerum sp. nov., isolated from diseased fish.

A taxonomic study was carried out on five Gram-staining-negative, catalase- and oxidase-positive, rod-shaped bacteria isolated from the gills and livers of five diseased rainbow trout. The five novel isolates were designated strains 687B-08(T), 445-08, 452-08, 453B-08 and 967B-08. In phylogenetic analyses based on 16S rRNA gene sequences, the five novel strains appeared almost identical (99.0-100 % sequence similarity) and to belong to the genus Chryseobacterium. Strain 687B-08(T) (the strain selected to represent the five novel isolates) was found to be most closely related to Chryseobacterium oncorhynchi 701B-08(T) (98.9% sequence similarity), Chryseobacterium ureilyticum F-Fue-04IIIaaaa(T) (98.6%), Chryseobacterium indologenes ATCC 29897(T) (98.3%), Chryseobacterium jejuense JS17-8(T) (98.1%) and Chryseobacterium gleum ATCC 35910(T) (98.1%). In DNA-DNA hybridizations, DNA-DNA relatedness values of 99-100% were recorded between the five novel strains. Lower DNA-DNA relatedness values (21-57%) were recorded between strain 687B-08(T) and C. oncorhynchi 701B-08(T), C. ureilyticum F-Fue-04IIIaaaa(T) and the type strains of other closely related, established species of the genus Chryseobacterium. The predominant respiratory quinone of strain 687B-08(T) was MK-6 and the major cellular fatty acids were iso-C(15:0), iso-C(17:1)ω9c, iso-C(17:0) 3-OH and C(16:1)ω6c. The G+C content of the genomic DNA of strain 687B-08(T) was 38.6 mol%. Based on the phenotypic and genotypic evidence, the five novel strains isolated from rainbow trout represent a single, novel species of the genus Chryseobacterium, for which the name Chryseobacterium viscerum sp. nov. is proposed. The type strain is 687B-08(T) ( = CECT 7793(T)  = CCUG 60103(T)).

Morphological variation between non-native lake- and stream-dwelling pumpkinseed Lepomis gibbosusin the Iberian Peninsula.

The objective of this study was to test if morphological differences in pumpkinseed Lepomis gibbosus found in their native range (eastern North America) that are linked to feeding regime, competition with other species, hydrodynamic forces and habitat were also found among stream- and lake- or reservoir-dwelling fish in Iberian systems. The species has been introduced into these systems, expanding its range, and is presumably well adapted to freshwater Iberian Peninsula ecosystems. The results show a consistent pattern for size of lateral fins, with L. gibbosus that inhabit streams in the Iberian Peninsula having longer lateral fins than those inhabiting reservoirs or lakes. Differences in fin placement, body depth and caudal peduncle dimensions do not differentiate populations of L. gibbosus from lentic and lotic water bodies and, therefore, are not consistent with functional expectations. Lepomis gibbosus from lotic and lentic habitats also do not show a consistent pattern of internal morphological differentiation, probably due to the lack of lotic-lentic differences in prey type. Overall, the univariate and multivariate analyses show that most of the external and internal morphological characters that vary among populations do not differentiate lotic from lentic Iberian populations. The lack of expected differences may be a consequence of the high seasonal flow variation in Mediterranean streams, and the resultant low- or no-flow conditions during periods of summer drought.

Response to azacitidine in patients with chronic myelomonocytic leukemia according to overlap myelodysplastic/myeloproliferative neoplasms criteria.

BACKGROUND: Azacitidine (AZA) is approved for the treatment of high-risk chronic myelomonocytic leukemia (CMML) of myelodysplastic (MD) subtype. Data of response rates using the specific response criteria for this disease are scarce. The aim of this study was to evaluate the response to AZA in patients diagnosed with CMML from the Spanish Registry of Myelodysplastic Syndromes (MDS) applying the overlap myelodysplastic/myeloproliferative neoplasms (MDS/MPN) response criteria. METHODS: We retrospectively studied 91 patients with CMML treated with at least one cycle of AZA from the Spanish Registry of MDS. As it was a real-world study, the response rate was evaluated between cycle 4 and 6, applying the MDS/MPN response criteria FINDINGS: The overall response rate at cycle 4-6 was 58%. Almost half of the patients achieved transfusion independence and one quarter showed clinical benefit, regardless of the CMML French-American-British (FAB) and World Health Organization (WHO) subtypes and CMML Specific Prognosis Scoring (CPSS) risk groups. Toxicity was higher in the MD-CMML subtype. INTERPRETATION: In our series, most CMML patients achieved an overall response rate with AZA according to the overlap-MDS/MPN response criteria regardless of the CMML FAB and WHO subtypes and CPSS risk groups. Thus, AZA may also be a treatment option for patients with the myeloproliferative CMML subtype and those with a lower-risk CPSS, but symptomatic.

Different methylation signatures at diagnosis in patients with high-risk myelodysplastic syndromes and secondary acute myeloid leukemia predict azacitidine response and longer survival.

BACKGROUND: Epigenetic therapy, using hypomethylating agents (HMA), is known to be effective in the treatment of high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy and/or allogeneic stem cell transplantation. However, response rates to HMA are low and there is an unmet need in finding prognostic and predictive biomarkers of treatment response and overall survival. We performed global methylation analysis of 75 patients with high-risk MDS and secondary AML who were included in CETLAM SMD-09 protocol, in which patients received HMA or intensive treatment according to age, comorbidities and cytogenetic. RESULTS: Unsupervised analysis of global methylation pattern at diagnosis did not allow patients to be differentiated according to the cytological subtype, cytogenetic groups, treatment response or patient outcome. However, after a supervised analysis we found a methylation signature defined by 200 probes, which allowed differentiating between patients responding and non-responding to azacitidine (AZA) treatment and a different methylation pattern also defined by 200 probes that allowed to differentiate patients according to their survival. On studying follow-up samples, we confirmed that AZA decreases global DNA methylation, but in our cohort the degree of methylation decrease did not correlate with the type of response. The methylation signature detected at diagnosis was not useful in treated samples to distinguish patients who were going to relapse or progress. CONCLUSIONS: Our findings suggest that in a subset of specific CpGs, altered DNA methylation patterns at diagnosis may be useful as a biomarker for predicting AZA response and survival.

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk.

Myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PV) and essential thrombocythemia (ET), and remarkably shortens survival. Although JAK2V617F and CALR allele burden are the main transformation risk factors, inflammation plays a critical role by driving clonal expansion toward end-stage disease. NF-κB is a key mediator of inflammation-induced carcinogenesis. Here, we explored the involvement of miR-146a, a brake in NF-κB signaling, in MPN susceptibility and progression. rs2910164 and rs2431697, that affect miR-146a expression, were analyzed in 967 MPN (320 PV/333 ET/314 MF) patients and 600 controls. We found that rs2431697 TT genotype was associated with MF, particularly with post-PV/ET MF (HR = 1.5; p < 0.05). Among 232 PV/ET patients (follow-up time=8.5 years), 18 (7.8%) progressed to MF, being MF-free-survival shorter for rs2431697 TT than CC + CT patients (p = 0.01). Multivariate analysis identified TT genotype as independent predictor of MF progression. In addition, TT (vs. CC + CT) patients showed increased plasma inflammatory cytokines. Finally, miR-146a-/- mice showed significantly higher Stat3 activity with aging, parallel to the development of the MF-like phenotype. In conclusion, we demonstrated that rs2431697 TT genotype is an early predictor of MF progression independent of the JAK2V617F allele burden. Low levels of miR-146a contribute to the MF phenotype by increasing Stat3 signaling.

The effect of Mn and B on the magnetic and structural properties of nanostructured Fe60Al40 alloys produced by mechanical alloying.

The effect of Mn and B on the magnetic and structural properties of nanostructured samples of the Fe60Al40 system, prepared by mechanical alloying, was studied by 57Fe Mössbauer spectrometry, X-ray diffraction and magnetic measurements. In the case of the Fe(60-x)Mn(x)Al40 system, 24 h milling time is required to achieve the BCC ternary phase. Different magnetic structures are observed according to the temperature and the Mn content for alloys milled during 48 h: ferromagnetic, antiferromagnetic, spin-glass, reentrant spin-glass and superparamagnetic behavior. They result from the bond randomness behaviour induced by the atomic disorder introduced by the MA process and from the competitive interactions of the Fe-Fe ferromagnetic interactions and the Mn-Mn and Fe-Mn antiferromagnetic interactions and finally the presence of Al atoms acting as dilutors. When B is added in the Fe60Al40 alloy and milled for 12 and 24 hours, two crystalline phases were found: a prevailing FeAl BCC phase and a Fe2B phase type. In addition, one observes an additional contribution attributed to grain boundaries which increases when both milling time and boron composition increase. Finally Mn and B were added to samples of the Fe60Al40 system prepared by mechanical alloying during 12 and 24 hours. Mn content was fixed to 10 at.% and B content varied between 0 and 20 at.%, substituting Al. X-ray patterns show two crystalline phases, the ternary FeMnAl BCC phase, and a (Fe,Mn)2B phase type. The relative proportion of the last phase increases when the B content increases, in addition to changes of the grain size and the lattice parameter. Such behavior was observed for both milling periods. On the other hand, the magnetic hyperfine field distributions show that both phases exhibit chemical disorder, and that the contribution attributed to the grain boundaries is less important when the B content increases. Coercive field values of about 10(2) Oe slightly increase with boron content. Comparison with previous results on FeAIB alloys shows that Mn promotes the structural stability of the nanostructured powders.

Computer vision-based analytical chemistry applied to determining iron in commercial pharmaceutical formulations.

Two different computer vision-based analytical chemistry (CVAC) methods were developed to quantify iron in the commercial pharmaceutical formulations Ferbisol® and Ferro sanol®. The methods involve using a digital camera or a desktop scanner to capture a digital image of a series of Fe2+ standard solutions and the unknown sample upon reaction with o-phenanthroline. The images are processed with appropriate software (e.g., the public domain programme ImageJ, from NIH) to obtain a numerical value (analytical signal) based on colour intensity. The fact that such a value is proportional to the analyte concentration allows one to construct a calibration graph from the standards and interpolate the value for the sample in order to determine its concentration. The results thus obtained were compared with those provided by a spectrophotometric method and the US Pharmacopoeia's recommended method. The differences never exceeded 2%. The two proposed methods are simple and inexpensive; also, they provide an effective instrumental alternative to spectrophotometric methods which can be especially beneficial in those cases where purchasing and maintaining a spectrophotometer is unaffordable.

Effect of the reaction medium on the characteristics of silanized titanium dioxide particles: Differences obtained in the Zeta potential data and infrared spectra.

In this document we present the differences in the Zeta potential and in the Infrared spectra data obtained from the characterization of silanized titanium dioxide particles, using two different solvents as reaction media: ethanol and toluene. Also, we provide micrographs of transmission electron microscopy in order to show morphological differences between the analyzed samples.

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.

QSPR studies on the photoinduced-fluorescence behaviour of pharmaceuticals and pesticides.

Fluorimetric analysis is still a growing line of research in the determination of a wide range of organic compounds, including pharmaceuticals and pesticides, which makes necessary the development of new strategies aimed at improving the performance of fluorescence determinations as well as the sensitivity and, especially, the selectivity of the newly developed analytical methods. In this paper are presented applications of a useful and growing tool suitable for fostering and improving research in the analytical field. Experimental screening, molecular connectivity and discriminant analysis are applied to organic compounds to predict their fluorescent behaviour after their photodegradation by UV irradiation in a continuous flow manifold (multicommutation flow assembly). The screening was based on online fluorimetric measurement and comprised pre-selected compounds with different molecular structures (pharmaceuticals and some pesticides with known 'native' fluorescent behaviour) to study their changes in fluorescent behaviour after UV irradiation. Theoretical predictions agree with the results from the experimental screening and could be used to develop selective analytical methods, as well as helping to reduce the need for expensive, time-consuming and trial-and-error screening procedures.