Volatile organic compounds (VOCs) in solid waste landfill cover soil: Chemical and isotopic composition vs. degradation processes.

Landfills for solid waste disposal release to the atmosphere a large variety of volatile organic compounds (VOCs). Bacterial activity in landfill cover soils can play an important role in mitigating VOC emission. In order to evaluate the effects of degradation processes and characterize VOCs composition in landfill cover soil, gases from 60 sites and along 7 vertical profiles within the cover soil were collected for chemical and isotopic analysis at two undifferentiated urban solid waste disposal sites in Spain: (i) Pinto (Madrid) and (ii) Zurita (Fuerteventura, Canary Islands). The CO2/CH4 ratios and δ13C-CO2 and δ13C-CH4 values were controlled by either oxidation or reduction processes of landfill gas (LFG). VOCs were dominated by aromatics, alkanes and O-substituted compounds, with minor cyclics, terpenes, halogenated and S-substituted compounds. Degradation processes, depending on both (i) waste age and (ii) velocity of the uprising biogas through the soil cover, caused (i) an increase of degradation products (e.g., CO2, O-substituted compounds) and (ii) a decrease of degradable components (e.g., CH4, alkanes, alkylated aromatics, cyclic and S-substituted compounds). Terpenes, halogenated compounds, phenol and furans were unaffected by degradation processes and only depended on waste composition. These results highlight the fundamental role played by microbial activity in mitigating atmospheric emissions of VOCs from landfills. Nevertheless, the recalcitrant behaviour shown by compounds hazardous for health and environment remarks the importance of a correct landfill management that has to be carried out for years after the waste disposal activity is completed, since LFG emissions can persist for long time.

Intrapatient functional clonality deconvoluted by coupling intracellular flow cytometry and next-generation sequencing in human leukemia.

The interplay between tumor heterogeneity and microenvironmental factors is a critical mechanism for clonal selection in leukemia. Evidence of unique clonal capacities to engraft within patient-derived xenograft (PDX) models suggests that intrapatient genetic architecture may be defined by functional differences at the clonal level. However, methods to detect functional differences assigned to genetically defined clones remain limited. Here, we describe a scalable method to directly measure the functional properties of clones within the same leukemia patient by coupling intracellular flow cytometry and next-generation sequencing (NGS). We provide proof of concept utilizing primary chronic myelmonocytic leukemia (CMML) samples and granulocyte-macrophage colony stimulating factor (GM-CSF) to elucidate the interaction between tumor heterogeneity and microenvironmental factors. Mixtures of human leukemia cell lines, with known response to GM-CSF, were used to validate the accuracy of our methodology. Using this approach, we confirm that our method is capable of discriminating GM-CSF sensitive cell lines, identifies somatic variants in primary leukemia samples, and resolves functional clonal architecture in an illustrative patient. Taken together, our data describes a novel method to determine intrapatient functional clonal heterogeneity and provides proof-of-concept for future investigation aimed at elucidating the clinical relevance of functional clonal differences.

Comparison of clinical outcomes and prognostic utility of risk stratification tools in patients with therapy-related vs de novo myelodysplastic syndromes: a report on behalf of the MDS Clinical Research Consortium.

While therapy-related (t)-myelodysplastic syndromes (MDS) have worse outcomes than de novo MDS (d-MDS), some t-MDS patients have an indolent course. Most MDS prognostic models excluded t-MDS patients during development. The performances of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Global Prognostic System (MPSS), WHO Prognostic Scoring System (WPSS) and t-MDS Prognostic System (TPSS) were compared among patients with t-MDS. Akaike information criteria (AIC) assessed the relative goodness of fit of the models. We identified 370 t-MDS patients (19%) among 1950 MDS patients. Prior therapy included chemotherapy alone (48%), chemoradiation (31%), and radiation alone in 21%. Median survival for t-MDS patients was significantly shorter than for d-MDS (19 vs 46 months, P<0.005). All models discriminated survival in t-MDS (P<0.005 for each model). Patients with t-MDS had a significantly higher hazard of death relative to d-MDS in every risk model, and had inferior survival compared to patients with d-MDS within all risk group categories. AIC Scores (lower is better) were 2316 (MPSS), 2343 (TPSS), 2343 (IPSS-R), 2361 (WPSS) and 2364 (IPSS). In conclusion, subsets of t-MDS patients with varying clinical outcomes can be identified using conventional risk stratification models. The MPSS, TPSS and IPSS-R provide the best predictive power.

Oil sands tailings ponds harbour a small core prokaryotic microbiome and diverse accessory communities.

Oil sands tailings ponds store the waste slurry generated by extracting bitumen from surface-mined oil (tar) sands ores. The ponds support diverse microbial communities involved in element cycling, greenhouse gas production, and hydrocarbon biodegradation that influence pond management and their environmental footprint. Since previous reports indicate that there are similar microbial metabolic functions amongst ponds, analogous microbiomes may be expected but ponds actually harbour distinct communities. Partial 16S rRNA gene pyrotag sequences from 95 samples were obtained from six ponds managed by three operators. From these we discerned a core prokaryotic microbiome, a subset of microbes shared amongst different samples, defined as operational taxonomic units (OTUs) at the lowest taxonomic level identifiable in individual ponds and pooled pond datatsets. Of the ∼1500-2700 OTUs detected per pond, 4-10 OTUs were shared among ≥75% of the samples per pond, but these few OTUs represented 39-54% of the ponds' sequence reads. Only 2-5 OTUs were shared by the majority of samples from all ponds. Thus the prokaryotic communities within these ponds consist of a few core taxa and numerous accessory members that likely afford resiliency and functional redundancy including roles in iron-, nitrogen- and sulfur-cycling, syntrophy, fermentation, and methanogenesis.

Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes.

Although next-generation sequencing has allowed for the detection of somatic mutations in myelodysplastic syndromes (MDS), the clinical relevance of variant allele frequency (VAF) for the majority of mutations is unknown. We profiled TP53 and 20 additional genes in our training set of 219 patients with MDS or secondary acute myeloid leukemia with findings confirmed in a validation cohort. When parsed by VAF, TP53 VAF predicted for complex cytogenetics in both the training (P=0.001) and validation set (P<0.0001). MDS patients with a TP53 VAF > 40% had a median overall survival (OS) of 124 days versus an OS that was not reached in patients with VAF <20% (hazard ratio (HR), 3.52; P=0.01) with validation in an independent cohort (HR, 4.94, P=0.01). TP53 VAF further stratified distinct prognostic groups independent of clinical prognostic scoring systems (P=0.0005). In multivariate analysis, only a TP53 VAF >40% was an independent covariate (HR, 1.61; P<0.0001). In addition, SRSF2 VAF predicted for monocytosis (P=0.003), RUNX1 VAF with thrombocytopenia (P=0.01) and SF3B1 with ringed sideroblasts (P=0.001). Together, our study indicates that VAF should be incorporated in patient management and risk stratification in MDS.

An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies.

Since its reclassification as a distinct disease entity, clinical research efforts have attempted to establish baseline characteristics and prognostic scoring systems for chronic myelomonocytic leukemia (CMML). Although existing data for baseline characteristics and CMML prognostication have been robustly developed and externally validated, these results have been limited by the small size of single-institution cohorts. We developed an international CMML data set that included 1832 cases across eight centers to establish the frequency of key clinical characteristics. Of note, we found that the majority of CMML patients were classified as World Health Organization CMML-1 and that a 7.5% bone marrow blast cut-point may discriminate prognosis with higher resolution in comparison with the existing 10%. We additionally interrogated existing CMML prognostic models and found that they are all valid and have comparable performance but are vulnerable to upstaging. Using random forest survival analysis for variable discovery, we demonstrated that the prognostic power of clinical variables alone is limited. Last, we confirmed the independent prognostic relevance of ASXL1 gene mutations and identified the novel adverse prognostic impact imparted by CBL mutations. Our data suggest that combinations of clinical and molecular information may be required to improve the accuracy of current CMML prognostication.

Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome.

In patients with chronic myelomonocytic leukemia (CMML), age>65 years is an adverse prognostic factor. Our objective in the current study was to examine risk factors for survival and treatment outcome in 261 'young' adults with CMML, as defined by age ⩽65 years. In multivariable analysis, lower HB (P=0.01), higher circulating blast % (P=0.002), ASXL1 (P=0.0007) and SRSF2 mutations (P=0.008) and Mayo-French cytogenetic stratification (P=0.04) negatively impacted survival. Similarly, leukemia-free survival was independently affected by higher circulating blast % (P<0.0001), higher bone marrow blast % (P=0.0007) and the presence of circulating immature myeloid cells (P=0.0002). Seventy-five (29%) patients received hypomethylating agents (HMA), with the median number of cycles being 5, and the median duration of therapy being 5 months. The over-all response rate was 40% for azacitidine and 30% for decitabine. Fifty-three (24%) patients underwent an allogeneic hematopoietic stem cell transplant (AHSCT), with a response rate of 56% and a non-relapse mortality of 19%. Survival in young adults with CMML, although higher than in older patients, is poor and even worse in the presence of ASXL1 and SRSF2 mutations. Treatment outcome was more impressive with AHSCT than with HMA and neither was influenced by ASXL1/SRSF2 mutations or karyotype.

Duchenne muscular dystrophy in a developing country: challenges in management and genetic counseling.

BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. METHODS: A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. RESULTS: There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to education programs. Mean age at death was 18.94 +/- 6.73 years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of DMD in Mexico is mainly caused by the late detection of first symptoms. There is no difference in early detection of symptoms between familiar and sporadic cases. Lifespan of patients in our cohort is reduced compared to developed countries. The late diagnosis and low percentage of definite cases may affect patient management and genetic counseling and could also preclude participation of patients into novel clinical trials.

Effect of pregestational diabetes mellitus on first trimester placental characteristics: three-dimensional placental volume and power Doppler indices.

OBJECTIVE: To investigate whether pregestational diabetes mellitus (DM) induces changes in vascular placental development detectable at first trimester. METHODS: This was a prospective case-control study in 69 women with pregestational DM and 94 controls undergoing first-trimester combined screening for aneuploidies. Maternal characteristics, fetal nuchal translucency thickness, maternal serum pregnancy-associated plasma protein A (PAPP-A) and free ß human chorionic gonadotrophin (ß-hCG) were evaluated. Three-dimensional ultrasound was used to measure placental volume and three dimensional power Doppler (3D-PD) placental vascular indices including: vascularization index (VI), flow index (FI) and vascularization flow index (VFI). Pregnancy-associated hypertensive complications (PAHC) and perinatal outcomes were analyzed. The total group of diabetic women and the group of diabetic women without PAHC were compared separately with the control group. RESULTS: 3D-PD placental vascular indexes were significantly lower in women with DM than in controls (VI p = 0.007, FI p = 0.003 and VFI p = 0.04). These differences remained on excluding cases with PAHC in the DM group. No differences were found in placental volumes between the DM group and controls. Serum PAPP-A levels were also lower in diabetic women (p < 0.02) and negatively correlated with the degree of maternal metabolic control at first trimester. CONCLUSIONS: Pregestational DM induces demonstrable alterations in first trimester placental development, with significantly reduced placental vascularization indices and PAPP-A values. This effect is independent of the later development of PAHC.

[Construction of model for calculating and recording neonatal weight percentiles]. / Construcción de un modelo de cálculo y registro del percentil de peso neonatal.

OBJECTIVES: To construct a model for calculating optimal foetal and neonatal weight curves with a method that allows automatic calculation of the percentile and sequential recording of results. MATERIAL AND METHODS: A model was constructed for calculating optimal weight and the corresponding percentiles for gestational age and sex from a sample of 23,578 newborns, after excluding cases with diseases. Birth weight was modelled using stepwise multiple regression analysis. Newborns were classified as small or large for gestational age (SGA or LGA) using the proposed model. The resulting classification was compared with those derived from other models designed for Spanish children. RESULTS: Optimal weight model: 3,311.062+68.074 *sex+143.267 *GE40 -13.481 *GE40(2) - 0.797 *GE40(3)+sex* (5.528 *GE40 - 0.674 *GE40(2) - 0.064 *GE40(3)). (GE, gestational age). Weight percentiles were obtained from standardized data using the coefficient of variation of the optimal weight. The degree of agreement between our model classification and those of the Carrascosa model and Ramos model, with empirical and smooth percentiles, was "almost perfect" (κ=0.866, κ=0.872, and κ=0.876 (P<.001), respectively), and between our model and that proposed by Figueras it was "substantial" (κ=0.720, P<.001). CONCLUSIONS: The new model is comparable to those used for Spanish children and allows accurate, updated automatic percentile calculation for gestational age and sex. The results can be digitally stored to track longitudinal foetal growth. Free access to the model is offered, together with the possibility of automatic calculation of foetal and neonatal weight percentiles.

Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes.

We evaluated the prognostic relevance of several clinical and laboratory parameters in 226 Mayo Clinic patients with chronic myelomonocytic leukemia (CMML): 152 (67%) males and median age 71 years. At a median follow-up of 15 months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented. In univariate analysis, significant risk factors for survival included anemia, thrombocytopenia, increased levels of white blood cells, absolute neutrophils, absolute monocyte count (AMC), absolute lymphocytes, peripheral blood and bone marrow blasts, and presence of circulating immature myeloid cells (IMCs). Spliceosome component (P=0.4) and ASXL1 mutations (P=0.37) had no impact survival. On multivariable analysis, increased AMC (>10 × 10(9)/l, relative risk (RR) 2.5, 95% confidence interval (CI) 1.7-3.8), presence of circulating IMC (RR 2.0, 95% CI 1.4-2.7), decreased hemoglobin (<10 g/dl, RR 1.6, 99% CI 1.2-2.2) and decreased platelet count (<100 × 10(9)/l, RR 1.4, 99% CI 1.0-1.9) remained significant. Using these four risk factors, a new prognostic model for overall (high risk, RR 4.4, 95% CI 2.9-6.7; intermediate risk, RR 2.0, 95% CI 1.4-2.9) and leukemia-free survival (high risk, RR 4.9, 95% CI 1.9-12.8; intermediate risk, RR 2.6, 95% CI 1.1-5.9) performed better than other conventional risk models and was validated in an independent cohort of 268 CMML patients.

[Duchenne muscular dystrophy: current aspects and perspectives on treatment]. / Distrofia muscular de Duchenne: actualidad y perspectivas de tratamiento.

INTRODUCTION AND DEVELOPMENT: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease of genetic origin that affects male children. It is characterized by progressive muscle deterioration which results in the patient becoming wheelchair-dependent until death from cardio-respiratory complications. A few years ago, DMD patients' life quality and expectancy were poor and treatment options limited; valuable recommendations that significantly delay the progress of the disease and improve the patient's life quality have been brought about recently. Numerous therapeutic approaches are now in development in order to correct the DMD genetic defect at molecular level. In the mean time, a comprehensive system to maintain patients in their best possible physical condition is needed. CONCLUSIONS: Accurate detection of complications enables caregivers to determine which patients are at higher risk and to provide treatment accordingly. Nevertheless, all of these efforts are dependent on early clinical and molecular diagnosis, careful record of clinical changes and long-term follow-up of DMD patients. Furthermore, the involvement of multidisciplinary groups and the patient's family is essential in said interventions.

Translation and psychometric properties of the kid's eating disorders survey (KEDS)-Spanish version.

OBJECTIVE: The objective of this study was to determine the psychometric properties of the Kid s Eating Disorders Survey (KEDS)-Spanish version [Cuestionario infantil para trastornos de la conducta alimentaria (CITCA)]. METHOD: The following instruments were applied to subjects aged 7-17 years: K-SADS-PL-MX, Eating Attitude Test-40 (EAT- 40) and CITCA (Spanish version of the KEDS). RESULTS: A total of 98 females, age 12.5 + 2.5 (7-17), participated. Cronbach's alpha coefficient for the total of the KEDS was 0.92. The scale items were grouped into two main components, which accounted for 74.4% of the variance. The convergent validity between the Spanish version of the KEDS and the EAT-40 was significant: r = 0.832 (p = 0.01). The criterion validity, on comparing the Spanish version of the KEDS with the K-SADS-PL-MX, was acceptable, with a r = 0.899 (p = 0.01). The test-retest at 15 days was positive: r = 0.967 (p = 0.01).

Fetal and neonatal habituation in infants of diabetic mothers.

OBJECTIVE: To evaluate whether maternal diabetes alters the habituation ability of fetuses and newborns. STUDY DESIGN: Two nonrandomized clinical trials were performed. First, we studied prenatal fetuses of women with pregestational diabetes, and control subjects matched for gestational age, and then we studied infants of diabetic mothers (IDM) and control subjects matched for gestational age and mode of delivery. Fetus and newborns were stimulated with vibroacoustic stimulus. RESULTS: In fetuses of diabetic mothers, the ability to habituate was lower, and the habituation rate was higher than in control subjects to all habituation tests. In the neonatal period, ability to habituate was lower (59% vs 100%; P< .001), and the habituation rate was higher (18 [14-21] vs 4 [1.2-6.8]; P< .001) in the IDM than in the control infants. We found a significant negative correlation between maternal glycosylated hemoglobin in each trimester of pregnancy and habituation ability in IDM. CONCLUSIONS: Fetuses and infants of diabetic mothers have impaired habituation ability, which is related to the degree of maternal metabolic control.

Risk factors for bacteremia in patients with limb cellulitis.

The aim of this study was to identify the risk factors for bacteremia in patients with limb cellulitis. Using the administrative and microbiology laboratory databases of a community teaching hospital, a review was conducted of all cases of community-acquired limb cellulitis that occurred during the period 1997-2004 and in which blood cultures had been performed. A comparison of demographical, clinical, and analytical data of patients with bacteremia versus patients without bacteremia was performed by univariate and multivariate analyses. Of 2,678 patients with cellulitis who presented to the hospital's emergency department, 308 were diagnosed with limb cellulitis and had blood cultures. Of these, 57 (18.5%) had bacteremia. In 24 of the 57 (42.1%) patients with bacteremia, the microorganism isolated in blood cultures was non-group-A beta-hemolytic Streptococcus, and in another 14 (24.6%), the microorganism identified was a gram-negative bacterium. Staphylococcus aureus was determined as the cause of bacteremia in just 6 (10.5%) patients and group A Streptococcus in 2 (3.5%). By logistic regression analysis, the following factors were associated with bacteremia: absence of previous antibiotic treatment (OR 5.3, 95% CI 1.4-20.3), presence of two or more comorbid factors simultaneously (OR 4.3, 95% CI 1.6-11.7), length of illness<2 days OR 2.44, 95% CI 1.07-5.56), and proximal limb involvement (OR 6, 95% CI 3.03-12.04). Patients with limb cellulitis who exhibit any of these characteristics are at increased risk of bacteremia. In such patients, it is imperative that blood cultures be performed.

[Antenatal care in immigrants]. / Control de gestación en inmigrantes.

The phenomenon of immigration has had an impact on the health care of the population. The immigrant population in Spain today represents approximately 8% of the total population. The majority of this population proceeds from countries with low income, and its origin and distribution is diverse. The immigrant population is characterised by its being young and healthy, and with a capacity to adapt to changes, but its social, economic and labour conditions are frequently insecure and favour vulnerability to disease. In spite of the number of immigrants of the male sex being globally higher than that of women, the percentage of immigrants of the female sex is growing. This increase of the female immigrant population has resulted in the appearance of specific health care needs, especially with respect to sexual and reproductive health. To which we must add a substantial increase in pathologies prevalent in the countries of origin, such as anaemia, tuberculosis, malnutrition, haemoglobinopathies, consanguinity, hypocalcaemia, hepatitis B and/or C, sexually transmitted infections, infectious diseases transmitted by arthropods, such as Chagas disease and other parasitoses, as well as genital mutilations. The aim of this article is to analyse the factors that make it difficult to control gestation in the immigrant population, as well as to establish guidelines for acting in antenatal care consultations. Insistence is placed on health education and prevention during pregnancy, and consideration is given to the appearance of rare diseases related to some of these groups.

Radioprotective effect of sodium diethyldithiocarbamate (DDC) and S-2-aminoethyl-isothioronicadenosin-5-triphosphate (adeturon) in gamma-irradiated Escherichia coli cells.

The effect of sodium diethyldithiocarbamate (DDC) and S-2-aminoethyl-isothiouronicadenosin-5-triphosphate (adeturon) in the induction of Escherichia coli SOS response promoted by gamma-irradiation was studied by measuring the induction of sulA gene and the induction of lambda prophage. Furthermore, as a way of measure the exonuclease activity in gamma-irradiated cells in the presence or absence of both compounds, the DNA degradation was determined. Adeturon did not affected DNA degradation, but inhibited the induction of the SOS functions studied. On the contrary, DDC inhibited DNA degradation as well as the induction of the sulA gene, but enhanced lambda induction in E. coli lysogenic strains. These results indicate that both compounds diminish the DNA damage produced by gamma-irradiation and also suggest that the mechanisms of radioprotection must be different. Thus, radioprotection mediated by DDC should involve free hydroxyl radical scavenging and a minor activity of exonuclease. The enhancement of phage induction in E. coli cells that DDC produces could be attributed to its quelant effect and this would not be not probably directly related to radioprotection. Adeturon, as thiols, may serve also as scavenging agent of free hydroxyl radicals, diminishing indirectly the DNA damage level. In addition, adeturon must interact with DNA in the same form that other aminothiol compounds do it. This interaction, mediated by amino groups of adeturon, may serve to concentrate these compounds near of the DNA damage site, increasing the potential for the thiol portion of the molecule to donate hydrogen, decreasing the damage level on DNA molecule. However, adeturon do not modify the exonuclease activity. Some topic about the possible clinical application of both compounds are discussed.