ctDNA quantification improves estimation of outcomes in patients with high-grade osteosarcoma: a translational study from the OS2006 trial.

BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.

Unexpected acute renal injury after high-dose etoposide phosphate and total body irradiation in children undergoing hematopoietic stem cell transplantation.

High-dose etoposide phosphate, a water-soluble prodrug of etoposide, may be used after total body irradiation (TBI) in pediatric allogeneic bone marrow transplantation for lymphoblastic leukemia. In a retrospective study of 21 children treated at the Nancy University Hospital (2000-2014), we identified unprecedentedly an unexpectedly high incidence (57%) of acute renal injury following etoposide phosphate infusion. Patients who developed renal function impairment experienced more severe mucositis but had outcomes similar to those who did not. No risk factors were identified. We speculate that the etoposide phosphate diluent, dextran 40, may have been the causative agent in these post-TBI renal toxicity cases.

Chromatographic Fingerprinting Strategy to Delineate Chemical Patterns Correlated to Coffee Odor and Taste Attributes.

Coffee cupping includes both aroma and taste, and its evaluation considers several different attributes simultaneously to define flavor quality and therefore requires complementary data from aroma and taste. This study investigates the potential and limits of a data-driven approach to describe the sensory quality of coffee using complementary analytical techniques usually available in routine quality control laboratories. Coffee flavor chemical data from 155 samples were obtained by analyzing volatile (headspace-solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS)) and nonvolatile (liquid chromatography-ultraviolet/diode array detector (LC-UV/DAD)) fractions, as well as from sensory data. Chemometric tools were used to explore the data sets, select relevant features, predict sensory scores, and investigate the networks between features. A comparison of the Q model parameter and root-mean-squared error prediction (RMSEP) highlights the variable influence that the nonvolatile fraction has on prediction, showing that it has a higher impact on describing acid, bitter, and woody notes than on flowery and fruity. The data fusion emphasized the aroma contribution to driving sensory perceptions, although the correlative networks highlighted from the volatile and nonvolatile data deserve a thorough investigation to verify the potential of odor-taste integration.

Analysis of environmental endocrine disrupting chemicals using the E-screen method and stir bar sorptive extraction in wastewater treatment plant effluents.

Endocrine disrupting chemicals (EDCs) have become a major issue in the field of environmental science due to their ability to interfere with the endocrine system. Recent studies show that surface water is contaminated with EDCs, many released from wastewater treatment plants (WWTP). This pilot study used biological (E-screen assay) and chemical (stir bar sorptive extraction-GC-MS) analyses to quantify estrogenic activity in effluent water samples from a municipal WWTP and in water samples of the recipient river, upstream and downstream of the plant. The E-screen assay was performed on samples after solid phase extraction (SPE) to determine total estrogenic activity; the presence of estrogenic substances can be evaluated by measuring the 17-beta-estradiol equivalency quantity (EEQ). Untreated samples were also assayed with an acute toxicity test (Vibrio fischeri) to study the correlation between toxicity and estrogenic disruption activity. Mean EEQs were 4.7 ng/L (+/-2.7 ng/L) upstream and 4.4 ng/L (+/-3.7 ng/L) downstream of the plant, and 11.1 ng/L (+/-11.7 ng/L) in the effluent. In general the WWTP effluent had little impact on estrogenicity nor on the concentration of EDCs in the river water. The samples upstream and downstream of the plant were non-toxic or weakly toxic (0

Identifying cloud forest conservation areas in Mexico from the potential distribution of 19 representative species.

Cloud forest is a sensitive and vulnerable ecosystem that is threatened by human activities as well as climate change. Previous studies have shown how transitional ecosystems such as cloud forests will be the most negatively impacted by the global increase in temperature. Therefore, the niche modeling framework was used in this study to geographically identify the areas with the climatic potential to host the largest number of key tree species in this ecosystem and to propose them as priority conservation areas. A total of 19 species were modeled using the MaxEnt algorithm; binary maps were generated for each species and combined to produce one potential suitability map and identify climatic priority areas. Thus, 7% of the national area of Mexico shows suitability for the cloud forest ecosystem, although it is currently distributed in less than 1% of the country. Finally, potential suitability areas were compared with natural protected areas, current land use and priority conservation areas. We found that of the current suitable area, only 5% coincides with some federal or state protection regime. Natural protected areas have proven to be a mechanism for forest conservation, so we must consider increasing the number and area of those protected areas that favor the conservation of these key cloud forest species.

Sorptive tape extraction in the analysis of the volatile fraction emitted from biological solid matrices.

Sorptive tape extraction (STE) is a recent sorption-based sampling technique in which a flexible polydimethylsiloxane (PDMS) tape is used to recover analytes at the surface of a solid matrix by direct contact as well as from the headspace in equilibrium with it. Solutes thus enriched on the inert PDMS material can be recovered either by solvent desorption or by thermo-desorption. The concentration capability of both direct contact and headspace STE was evaluated by sampling (a) aromatic plants to study the reaction of a vegetable matrix submitted to stress, and (b) fruits at the surface of the pulp or inside the pulp; the composition of the volatile fraction released from the skin when a perfume is sprayed on the back of the hand was also studied. The concentration capability of direct contact and headspace STE was compared to that of HSSE with a 20 microL PDMS twister and HS-SPME with a PDMS 100 microm fibre, by determining the relative abundances (RA) of the characterizing components of the aromatic plants under investigation. Repeatability and influence of tape surface on STE recovery were also evaluated.

[Therapeutic education in asthma management]. / La educación terapéutica en el asma.

All guidelines, protocols and recommendations underline the importance of therapeutic education as a key element in asthma management and control. Considerable evidence supports the efficacy and effectiveness of this measure. Health personnel, as well as patients and their parents, can and should be educated with two main objectives: to achieve the best possible quality of life and to allow self control of the disease. These goals can be attained through an educational process that should be individually tailored, continuous, progressive, dynamic, and sequential. The process poses more than a few difficulties involving patients, health professionals, and the health systems. Knowledge of the various psychological factors that can be present in asthmatic patients, as well as the factors related to the highly prevalent phenomenon of non-adherence, is essential. Awareness of the factors influencing physician-patient-family communication is also highly important to achieve the objectives set in therapeutic education. The educational process helps knowledge and abilities to be acquired and allows attitudes and beliefs to be modified. Patients and caregivers should be provided with an individual written action plan based on symptoms and/or forced expiratory volume in 1 second. Periodic follow-up visits are also required.

Long term variations measurement of electromagnetic field exposures in Alcalá de Henares (Spain).

Electromagnetic radiowave exposure is a major concern in most countries due to possible adverse health effects. Over the last 10years, many technological changes (digital television, mobile technologies, wireless networks…) have led to variations in the electromagnetic field (EMF) levels. A large number of studies devoted to the analysis of EMF levels with personal dosimeters or computer models of the exposure of mobile stations have been conducted. However, the study of the exposure values, taking into account all the existing sources, and their evolution in a wide area, using measurements, has rarely been performed. In this paper, we provide a comparison of the EMF exposure levels for the city of Alcalá de Henares (Spain) over a ten-year period using a broadband isotropic probe in the range from 100kHz to 3GHz. A statistical and spatial analysis of the measurements and their variations are also presented for the study of the global and local variations. The measured values in the period from 2006 to 2015 were ranging from 0.02 to 2.05V/m. Our global results show a moderate increase from 2006 to 2010 and they are almost invariant from 2010 to 2015. Although the whole dataset does not have relevant statistical difference, we have found marked local differences. In the city areas where the population density has remained unaltered, we have measured lower exposure levels. Conversely, new urban and industrial developments have demanded new resources, which have potentially contributed to the observed increase in the measured electric field levels within these areas.

Cinética del lactato para el pronóstico en el shock cardiogénico asistido con oxigenador extracorpóreo de membrana venoarterial / Lactate levels as a prognostic predict in cardiogenic shock under venoarterial extracorporeal membrane oxygenation support

Introducción y objetivos: El lactato y su evolución se asocian con el pronóstico de los pacientes en shock, si bien es escasa la evidencia en aquellos asistidos con oxigenador extracorpóreo de membrana venoarterial (ECMO-VA). Nuestro objetivo es evaluar su valor pronóstico en shock cardiogénico asistido con ECMO-VA. Métodos: Estudio de pacientes tratados con ECMO-VA por shock cardiogénico de indicación médica entre julio de 2013 y abril de 2021. Se calculó el aclaramiento de lactato: (lactato inicial − lactato 6 h) / lactato inicial × tiempo exacto entre ambas determinaciones. Resultados: De 121 pacientes, 44 (36,4%) tenían infarto agudo de miocardio; 42 (34,7%), implante intraparada; 14 (11,6%), tromboembolia pulmonar, 14 (11,6%), tormenta arrítmica y 6 (5,0%), miocarditis fulminante. A los 30 días habían fallecido 60 pacientes (49,6%); la mortalidad fue mayor con el implante intraparada que con el implante en circulación espontánea (30 [71,4%] de 42 frente a 30 [38,0%] de 79; p=0,030). Se asociaron de manera independiente con la mortalidad a 30 días la alanina aminotransferasa (ALT) antes del implante y el lactato (tanto basal como a las 6 h y el aclaramiento). Los modelos de regresión que incluían el lactato presentaron mejor capacidad predictiva de la supervivencia que las puntuaciones ENCOURAGE y ECMO-ACCEPTS, con mayor área bajo la curva ROC en el modelo con lactato a las 6 h.Conclusiones: El lactato (basal y a las 6 h y el aclaramiento) es un predictor independiente para el pronóstico de los pacientes en shock cardiogénico asistidos con ECMO-VA que facilita una mejor estratificación del riesgo y tiene una capacidad predictiva superior (AU)

Introduction and objectives: Lactate and its evolution are associated with the prognosis of patients in shock, although there is little evidence in those assisted with an extracorporeal venoarterial oxygenation membrane (VA-ECMO). Our objective was to evaluate its prognostic value in cardiogenic shock assisted with VA-ECMO. Methods: Study of patients with cardiogenic shock treated with VA-ECMO for medical indication between July 2013 and April 2021. Lactate clearance was calculated: [(initial lactate − 6 h lactate) / initial lactate × exact time between both determinations]. Results: From 121 patients, 44 had acute myocardial infarction (36.4%), 42 implant during cardiopulmonary resuscitation (34.7%), 14 pulmonary embolism (11.6%), 14 arrhythmic storm (11.6%), and 6 fulminant myocarditis (5.0%). After 30 days, 60 patients (49.6%) died, mortality was higher for implant during cardiopulmonary resuscitation than for implant in spontaneous circulation (30 of 42 [71.4%] vs 30 of 79 [38.0%], P=.030). Preimplantation GPT and lactate (both baseline, at 6hours, and clearance) were independently associated with 30-day mortality. The regression models that included lactate clearance had a better predictive capacity for survival than the ENCOURAGE and ECMO-ACCEPTS scores, with the area under the ROC curve being greater in the model with lactate at 6 h. Conclusions: Lactate (at baseline, 6h, and clearance) is an independent predictor of prognosis in patients in cardiogenic shock supported by VA-ECMO, allowing better risk stratification and predictive capacity (AU)

[Nephrolitiasis in a patient with cystic fibrosis]. / Nefrolitiasis en un paciente con fibrosis quística.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Defects in the CFTR gene cause abnormal chloride conductance across the apical membrane of epithelial cells, which results in progressive lung disease and also affects other organs. Because life expectancy has increased, other complications of CF have become more apparent. We present a patient with CF and symptomatic nephrolithiasis. Several stones were evident in both kidneys. A 24-hour urine sample showed hyperoxaluria (141 mg/24 h/ 1.73 m(2)) and hypocitraturia and (206 mg/24 h/1.73 m(2), 177 mg citrate/g creatinine). Nephrolithiasis should be included in the differential diagnosis of patients with CF and abdominal pain; urinary excretion of oxalate and citrate should be investigated.

High-speed gas chromatography with direct resistively-heated column (ultra fast module-GC)-separation measure (S) and other chromatographic parameters under different analysis conditions for samples of different complexities and volatilities.

The influence of GC speed on the separation capability of a chromatographic system is reported measuring a series of parameters including separation measure (S), peak capacity (n), peak width (w), analysis time, t(b) (determined on the last eluting compound) and separation measure/analysis time ratio (S/t(b)) determined by analyzing a bergamot essential oil sample and a standard mixture of pesticides. Conventional GC, fast GC (with 10 m (FGC10) and 5 m (FGC5) narrow-bore columns), and direct resistively-heated ultra fast module-GC (UFM-GC) were the GC speed approaches used. The influence of different heating rates with a constant flow for FGC5, FGC 10, and UFM-GC and with variable flows for UFM-GC on S, n, w, S/t(b), and t(b) was also studied. The results of this study show that: (a) separation capability of the chromatographic system (i.e. S and n) and analysis time depend on the GC approaches. Within each GC approach, S and n and analysis time depend on the heating rates, although to a different extent, and S and n decrease much less than the gain in analysis time, in particular when fast heating rates are applied; (b) in UFM-GC, the loss of separation capability with heating rate can also be partially compensated by the choice of an appropriate flow rate that, within each heating rate, may contribute to increase S while reducing t(b); (c) within a specific GC approach, the chromatographic system (column and stationary phase) and conditions (heating and flow rates) must be such to achieve a suitable S-value when two analytes must be separated with a given resolution in a minimum analysis time.

Isolation from alfalfa of resistance gene analogues containing nucleotide binding sites.

Cloned resistance (R) genes from a broad range of plant species are known to share similarities in DNA sequence and structural motifs. Degenerate oligonucleotide primers designed from conserved regions of the nucleotide binding site (NBS), common to many R genes, were used to amplify the NBS regions from genomic DNA from alfalfa ( Medicago sativa L). Sequence comparisons of the amplified fragments indicated that at least 18 families of NBS-containing R genes are present in alfalfa. Comparisons to R genes from other species suggested a polyphyletic origin of these gene families. Using the same degenerate primers, PCR analysis of cDNA prepared from a plant not challenged with a pest or pathogen revealed that many of the NBS-containing gene families were transcribed actively. Amplification of NBS regions from other Medicago species showed the presence of some NBS-containing genes not present in alfalfa. These results indicate that the NBS-containing R genes comprise a large gene family in Medicago, at least some of which are transcribed in healthy plants, and that different Medicago species carry unique NBS genes.

Clinical evaluation of pediculicidal and ovicidal efficacy of two pyrethrin-piperonyl-butoxide formulations.

The pediculicidal and ovicidal efficacy of two pyrethrin-piperonyl-butoxide agents was evaluated in 40 children infested with head lice. Both commercial products, a lotion and a shampoo, had similar formulations. Specifically, the shampoo vehicle was tested to determine whether its surface-tension-lowering action made it more effective as an ovicidal agent than the lotion. Results of the study indicate that the shampoo is 49% more effective than the lotion as an ovicide.

A cytotoxic diarylheptanoid from Viscum cruciatum.

A diarylheptanoid, 1,7-di-(3',4'-dihydroxyphenyl)-4-hepten-3-one, hirsutanone, has been isolated from the methanolic extract of the aerial parts of Viscum cruciatum (Viscaceae) and characterized by spectroscopic methods and chemical transformations. This compound showed cytotoxic activity against melanoma (UACC-62), renal (TK-10) and breast (MCF-7) cancer cell lines.

Cytotoxic compounds from Annonaceus species as DNA topoisomerase I poisons.

BACKGROUND: In the search for cytotoxic natural products as DNA topoisomerase poisons, we have assessed six annonaceus compounds (the acetogenins annonacin and rolliniastatin-1, the styryl-lactones etharversin and altholactone and the alkaloids thaligrisine and cepharanone-B) for cytotoxic activity against three human cancer cell lines and then we evaluated these compounds as DNA topoisomerase poisons. MATERIALS AND METHODS: The cytotoxicity parameters were determined following protocols established by the National Cancer Institute (NCI) using the SRB assay. In the topoisomerase assay, the supercoiled DNA produces open circle forms that are stabilised in the presence of DNA topoisomerase poisons and can be detected after a denaturation step by proteinase K-SDS. RESULTS: The six compounds showed cytotoxic activity, with cepharanone B being the most cytotoxic one, even more than the antineoplastic agent etoposide on two cancer cell lines, although it is the only one that does not act as a DNA topoisomerase poison. CONCLUSION: These results could justify the traditional use of the studied annonaceus species and topoisomerase-mediated DNA damage might be a possible mechanism by which five of these compounds exert their cytotoxicity.

A dosing study of nonoxynol-9 and genital irritation.

The objective of the study was to assess the symptoms and signs of genital irritation produced by different frequencies of nonoxynol-9 (N-9) use. Thirty-five women were randomized to each of 5 groups and used a vaginal suppository for 2 weeks. Group 1: N-9 once every other day; Group 2: N-9 once a day; Group 3: N-9 twice a day; Group 4: N-9 4 times a day; and Group 5: placebo 4 times a day. Study women were examined at admission, one week and 2 weeks with a colposcope for erythema and epithelial disruption, and were interviewed about vaginal itching and burning. The rates of reported symptoms for N-9 users were not significantly different from that of placebo users. The rate of epithelial disruption for women using N-9 every other day was essentially the same as that of women using placebo. The rates of epithelial disruption for women using N-9 1/day and 2/day were 2.5 times greater than that of placebo users. The rate of epithelial disruption for women using N-9 4/day was five times greater than that of placebo users. Genital irritation was located primarily on the vagina or cervix, and vulvitis was not a significant problem. Women who infrequently use N-9 products may not experience an increase in genital irritation. Women who choose to use N-9 frequently may experience an increase in epithelial disruption.

Determination of daminozide residues in apple pulp using HPLC-DAD-UV.

This paper reports an HPLC-UV method to determine daminozide residues in apple pulps adopting the recently introduced EU limit of 0.01 mg/kg for baby food preparation (Commission Directive 1999/39/CE). The method is based on alkaline hydrolysis of daminozide to N',N'-dimethylhydrazine (UDMH), which is recovered by distillation and subsequently derivatizated with salicyl aldehyde to salicyl aldehyde-N,N-dimethylhydrazone under strongly basic conditions. The resulting solution was cleaned up with Extrelut 20 NT and dichloromethane as eluent, then analyzed by HPLC with a C18 column and a mobile phase programmed from 50:50 AcCN/H(2)O to 100% AcCN. The salicyl aldehyde-N,N-dimethylhydrazone was selectively detected through two diagnostic UV absorption maxima at 295 and 325 nm, which have strong molar absorbivities. Recoveries of daminozide at 0.01 mg/kg were above 80%. The limits of detection (LODs) of salicyl aldehyde-N,N-dimethylhydrazone expressed as daminozide concentration were 100 pg/microL at 295 nm and 150 pg/microL at 325 nm, and the limits of quantitation (LOQs) of daminozide were 0.0013 mg/kg at 295 nm and 0.0022 mg/kg at 325 nm.

Acetic-acid guided visual inspection vs. cytology-based screening for cervical cancer in the Philippines.

OBJECTIVES: To compare the validity and acceptability of acetic-acid visualization (VIA), magnified acetic-acid visualization (VIAM), spatula+cotton swab-Papanicolaou (Pap) smear (SS), and cervical brush-Pap smear (CB) in the detection of precursor/early cervical cancer lesions. METHODS: A total of 12992 women aged between 25 and 65 years from 14 Philippine centers were randomly allocated to the four tests. The gold standard was colposcopy with biopsy for positive/suspicious cases. RESULTS: Sensitivity rates [95% confidence intervals (CIs)] were 37 (CI, 26.8-48.5), 34.1 (CI, 24.8-44.8), 14.3 (CI, 6.4-27.8), and 19.1 (CI, 9.2-34.6) for VIA, VIAM, SS, and CB, respectively. Specificity rates were 90.7 (CI, 89.6-91.7), 90.7 (CI, 89-91.1), 97.5 (CI, 96.8-98), and 97.9 (CI, 97.3-98.4), respectively. Kappa for the Pap smear (PS) within centers ranged from -0.154 to 0.783, and between centers from -0.028 to 0.364. Screeners preferred CB; screened-women preferred VIA. CONCLUSIONS: The acetic-acid visualization and VIAM methods are recommended for initial cervical cancer screening in the Philippines.

Simultaneous determination of six triazolic pesticide residues in apple and pear pulps by liquid chromatography with ultraviolet diode array detection.

A method is described for the simultaneous determination of diclobutrazol, flusilazole, flutriafol, hexaconazole, paclobutrazol, and tetraconazole in apple and pear pulps used in baby food at a limit of 0.01 mg/kg. Apple and pear pulp samples are subjected to selective solid-phase microdispersion (SPMD) with SPE-ED Matrix-38 and acetone-cyclohexane, and the extracts are cleaned up on a Florisil cartridge with hexane-cyclohexane-acetone. The extracts are then analyzed by liquid chromatography with ultraviolet detection, using an octadecylsilane column with a gradient-programmed acetonitrile-water mobile phase. Recoveries were determined by spiking apple and pear pulps with the 6 pesticides under investigation at 0.1, 0.05, 0.03, and 0.01 mg/kg. Six determinations were performed at each level for each pesticide. Recoveries were > or = 70% at the 0.01 mg/kg level.

Naftifine cream in the treatment of cutaneous candidiasis.

Naftifine, a member of a new class of synthetic antifungal drugs, the allylamines, was evaluated for the treatment of cutaneous candidiasis. In a double-blind, parallel-group clinical trial, sixty patients with cutaneous candidiasis were randomly assigned to receive either naftifine cream 1 percent or its vehicle twice a day for three weeks. Two weeks after the end of therapy, 77 percent of the naftifine-treated patients were mycologically cured (negative results on potassium hydroxide preparations and culture) and had no clinically apparent disease, compared with 3 percent of the patients treated with vehicle (p less than 0.001). Side effects reported with naftifine cream were few and minor.