Association between mediterranean diet and metal(loid) exposure in 4-5-year-old children living in Spain.

Even relatively low levels of metals exposure may impact health, particularly among vulnerable populations such as infants and young children. However, little is known about the interplay between simultaneous metal exposures, common in real-life scenarios, and their association with specific dietary patterns. In this study, we have evaluated the association between adherence to Mediterranean diet (MD) and urinary metal concentrations individually and as an exposure mixture in 713 children aged 4-5-years from the INMA cohort study. We used a validated food frequency questionnaire to calculate two MD indexes scores: aMED and rMED. These indexes gather information on various food groups within the MD and score differently. To measure urinary concentrations of cobalt, copper, zinc, molybdenum, selenium, lead, and cadmium as exposure biomarkers, we used inductively coupled plasma mass spectrometry (ICP-MS), coupled with an ion chromatography (IC) equipment for arsenic speciation analysis. We applied linear regression and quantile g-computation, adjusted for confounders, to analyse the association between MD adherence and exposure to the metal mixture. High adherence to MD such as the quintile (Q) 5 MD was associated with higher urinary arsenobetaine (AsB) levels than Q1, with ß values of 0.55 (confidence interval - CI 95% 0.01; 1.09) for aMED and 0.73 (CI 95% 0.13; 1.33) for rMED. Consumption of fish was associated with increased urinary AsB but reduced inorganic arsenic concentrations. In contrast, the aMED vegetables consumption increased urinary inorganic arsenic content. A moderate level of adherence to MD (Q2 and Q3) was associated with lower copper urinary concentrations than Q1, with ß values of -0.42 (CI 95% -0.72; -0.11) for Q2 and -0.33 (CI 95% -0.63; -0.02) for Q3, but only with aMED. Our study, conducted in Spain, revealed that adhering to the MD reduces exposure to certain metals while increasing exposure to others. Specifically, we observed increase in exposure to non-toxic AsB, highlighting the significance of consuming fish/seafood. However, it is crucial to emphasize the necessity for additional efforts in reducing early-life exposure to toxic metals, even when adhering to certain food components of the MD.

KRAS p.G12C mutation occurs in 1% of EGFR-mutated advanced non-small-cell lung cancer patients progressing on a first-line treatment with a tyrosine kinase inhibitor.

BACKGROUND: KRAS is mutated in ∼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. MATERIALS AND METHODS: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. RESULTS: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. CONCLUSIONS: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature.

Bone marrow storage and delayed consumption at Middle Pleistocene Qesem Cave, Israel (420 to 200 ka).

Bone marrow and grease constitute an important source of nutrition and have attracted the attention of human groups since prehistoric times. Marrow consumption has been linked to immediate consumption following the procurement and removal of soft tissues. Here, we present the earliest evidence for storage and delayed consumption of bone marrow at Qesem Cave, Israel (~420 to 200 ka). By using experimental series controlling exposure time and environmental parameters, combined with chemical analyses, we evaluated bone marrow preservation. The combination of archaeological and experimental results allowed us to isolate specific marks linked to dry skin removal and determine a low rate of marrow fat degradation of up to 9 weeks of exposure. This is the earliest evidence of such previously unidentified behavior, and it offers insights into the socio-economy of the human groups who lived at Qesem and may mark a threshold to new modes of Palaeolithic human adaptation.

Intersubband absorption in GaN nanowire heterostructures at mid-infrared wavelengths.

In this paper, we study intersubband characteristics of GaN/AlN and GaN/Al0.4Ga0.6N heterostructures in GaN nanowires structurally designed to absorb in the mid-infrared wavelength region. Increasing the GaN well width from 1.5 to 5.7 nm leads to a red shift of the intersubband absorption from 1.4 to 3.4 µm. The red shift in larger quantum wells is amplified by the fact that one of the GaN/AlN heterointerfaces (corresponding to the growth of GaN on AlN) is not sharp but rather a graded alloy extending around 1.5-2 nm. Using AlGaN instead of AlN for the same barrier dimensions, we observe the effects of reduced polarization, which blue shifts the band-to-band transitions and red shifts the intersubband transitions. In heavily doped GaN/AlGaN nanowires, a broad absorption band is observed in the 4.5-6.4 µm spectral region.

New interpretation of the Gran Dolina-TD6 bearing Homo antecessor deposits through sedimentological analysis.

Gran Dolina is a cavity infilled by at least 25 m of Pleistocene sediments. This sequence contains the TD6 stratigraphic unit, whose records include around 170 hominin bones that have allowed the definition of a new species, Homo antecessor. This fossil accumulation was studied as a single assemblage and interpreted as a succession of several human home bases. We propose a complete stratigraphic context and sedimentological interpretation for TD6, analyzing the relationships between the sedimentary facies, the clasts and archaeo-palaeontological remains. The TD6 unit has been divided into three sub-units and 13 layers. Nine sedimentary facies have been defined. Hominin remains appear related to three different sedimentary facies: debris flow facies, channel facies and floodplain facies. They show three kinds of distribution: first a group of scattered fossils, then a group with layers of fossils in fluvial facies, and third a group with a layer of fossils in mixed fluvial and gravity flow facies. The results of this work suggest that some of these hominin remains accumulated in the cave by geological processes, coming from the adjacent slope above the cave or the cave entry, as the palaeogeography and sedimentary characteristics of these allochthonous facies suggest.

Optimization of pre-emptive isolations in a polyvalent ICU through implementation of an intervention strategy.

BACKGROUND: Pre-emptive isolation refers to the application of contact precaution measures in patients with strongly suspected colonization by multiresistant bacteria. OBJECTIVE: To assess the impact of an intervention program involving the implementation of a consensus-based protocol of pre-emptive isolation (CPPI) on admission to a polyvalent ICU of a general hospital. METHODS: A comparative analysis of 2 patient cohorts was made: a historical cohort including patients in which pre-emptive isolation was established according to physician criterion prior to starting CPPI (from January 2010 to February 2011), and a prospective cohort including patients in which CPPI was implemented (from March to November 2011). CPPI included the identification and diffusion of pre-emptive isolation criteria, the definition of sampling methodology, the evaluation of results, and the development of criteria for discontinuation of pre-emptive isolation. Pre-emptive isolation was indicated by the medical staff, and follow-up was conducted by the nursing staff. Pre-emptive isolation was defined as "adequate" when at least one multiresistant bacteria was identified in any of the samples. Comparison of data between the 2 periods was made with the chi-square test for categorical variables and the Student t-test for quantitative variables. Statistical significance was set at P<.05. RESULTS: Among the 1,740 patients admitted to the ICU (1,055 during the first period and 685 during the second period), pre-emptive isolation was indicated in 199 (11.4%); 111 (10.5%) of these subjects corresponded to the historical cohort (control group) and 88 (12.8%) to the posterior phase after the implementation of CPPI (intervention group). No differences were found in age, APACHE II score or patient characteristics between the 2 periods. The implementation of CPPI was related to decreases in non-indicated pre-emptive isolations (29.7 vs. 6.8%, P<.001), time of requesting surveillance cultures (1.56 vs. 0.37 days, P<.001), and days of duration of treatment (4.77 vs. 3.58 days, P<.001). In 44 patients (22.1%) in which pre-emptive isolation was indicated, more than one multiresistant bacteria was identified, with an "adequate pre-emptive isolation rate" of 19.8% in the first period and 25.0% in the second period (P<.382). CONCLUSIONS: The implementation of CPPI resulted in a significant decrease in pre-emptive isolations which were not indicated correctly, a decrease in the time elapsed between isolation and collection of samples, and a decrease in the duration of isolation measures in cases in which isolation was unnecessary, without increasing the rate of "adequate pre-emptive isolation".

Alkaline cyanide degradation by Pseudomonas pseudoalcaligenes CECT5344 in a batch reactor. Influence of pH.

Water containing cyanide was biologically detoxified with the bacterial strain Pseudomonas pseudoalcaligenes CECT5344 in a batch reactor. Volatilization of toxic hydrogen cyanide (HCN) was avoided by using an alkaline medium for the treatment. The operational procedure was optimized to assess cyanide biodegradation at variable pH values and dissolved oxygen concentrations. Using an initial pH of 10 without subsequent adjustment allowed total cyanide to be consumed at a mean rate of approximately 2.81 mg CN(-) L(-1) O.D.(-1) h(-1); however, these conditions posed a high risk of HCN formation. Cyanide consumption was found to be pH-dependent. Thus, no bacterial growth was observed with a controlled pH of 10; on the other hand, pH 9.5 allowed up to 2.31 mg CN(-) L(-1) O.D.(-1) h(-1) to be converted. The combination of a high pH and a low dissolved oxygen saturation (10%) minimized the release of HCN. This study contributes new basic knowledge about this biological treatment, which constitutes an effective alternative to available physico-chemical methods for the purification of wastewater containing cyanide or cyano-metal complexes.

Nódulo de la Hermana María José. Manifestación inicial de un carcinoma de ovario / Sister Mary Joseph’s nodule. A first manifestation of ovarian carcinoma

Las metástasis umbilicales de neoplasias malignas (también denominadas nódulo de la Hermana María José) son un suceso raro que normalmente se considera un signo de mal pronóstico. A pesar de ello, el tiempo de supervivencia puede alargarse con un tratamiento agresivo que combine la cirugía y la quimioterapia. Se presenta un caso de metástasis umbilical como manifestación inicial de un carcinoma de ovario, tratado con una óptima cirugía debulking y quimioterapia, y con seguimiento regular desde la operación. La paciente continúa en remisión clínica completa, su estado general es bueno y, 36 meses después, los marcadores tumorales se mantienen en valores normales (AU)

Umbilical metastases from malignant neoplasms, also termed Sister Mary Joseph's nodule, are rare and have usually been considered as a sign of poor prognosis. However, patient survival time could be lengthened by aggressive therapy that combines surgery with chemotherapy. We report a case of umbilical metastases as the presenting symptom of an ovarian carcinoma. Treatment consisted of optimal debulking surgery plus chemotherapy and regular postoperative follow-up was performed. The patient has been in complete clinical remission with good performance status and normal levels of serum tumor markers for 36 months (AU)

Estabilidad de la 99mTc-tetrofosmina en función de envase, tiempo y temperatura de incubación / The infl uence of storage vessel, incubation time and temperature on the stability of 99mTc-tetrofosmin

Observar si el almacenamiento de la 99mTc-tetrofosmina durante el tiempo indicado por el fabricante de estabilidad del radiofármaco, 12 horas, a diferentes temperaturas (18-25º C o Tª ambiente, 32º C y 4-8º C), podría infl uir en la PRQ del radiofármaco y en su estabilidad, ya sea en los mismos viales del equipo reactivo como en jeringas. Del mismo modo, estudiar si la incubación requerida para la preparación del radiofármaco (20 min) va a afectar a la PRQ de la dosis si ésta ha sido cargada antes o después de ese tiempo. Material y Métodos: Los 40 viales de la fosfi na se marcaron siguiendo las indicaciones del fabricante. Se estudiaron 3 condiciones de almacenamiento en función de la temperatura en la que mantuviéramos el radiofármaco, para estudiar las condiciones ambientales extremas en las que se puede encontrar una dosis del fármaco. Resultados: Los valores medios de la PRQ (%) cuando el radiofármaco se incubaba en vial o en jeringa fueron de 95,79±2,32 y 96,16±2,32 respectivamente, no observándose diferencias en los valores. La estabilidad del radiofármaco a distintas temperaturas, y a diferentes tiempos fueron superiores al 90% en todos los casos. Conclusiones: El complejo 99mTc-tetrofosmina es estable durante 12 horas tanto si la incubación se realiza en el vial original del equipo reactivo como si se realiza en jeringa de insulina con aguja. El radiofármaco es estable durante 12 horas a diferentes temperaturas de almacenamiento

Aim: To determine the stability and radio chemical purity (RCP) of 99mTc-tetrofosmin kept for different time intervals of up to 12 hours, the maximum recommended by the manufacturers, at different temperatures (18-25º C or room temperature, 32ºC & 2-8ºC), in both reactive equipment vials or in syringes, and to determine whether shorter or longer incubation times, other than the recommended 20 minute period, could affect the RCP of doses of the radiopharmaceutical. Materials and Methods: 40 vials of phosphine were labelled in accordance with manufacturer’s recommendations. Three different storage temperature conditions were studied, in order to determine how possible extremes may affect dosages of the drug. Results: The average RCP percentages of the radiofarmaceutical incubated in vials and syringes were 95.79±2.32 & 96.16±2.32 respectively, with no signifi cant differences observed. Stability at different temperatures and different time intervals was over 90% in all cases. Conclusions: The 99mTc-tetrofosmin complex remains stable for 12 hours, whether it is incubated in the original reactive equipment or within insulin syringes with needle. Additionally, the radiopharmaceutical also remained stable at the different studied storage temperatures and at all time intervals for up to 12 hours

Interactions between nitrate assimilation and 2,4-dinitrophenol cometabolism in Rhodobacter capsulatus E1F1.

The phototrophic, nitrate-photoassimilating bacterium Rhodobacter capsulatus E1F1 cometabolizes 2,4-dinitrophenol (DNP) by photoreducing it to 2-amino-4-nitrophenol under anaerobic conditions. DNP uptake and nitrate metabolism share some biochemical features, and in this article we show that both processes are influenced by each other. Thus, as was demonstrated for nitrate assimilation, DNP uptake requires a thermolabile periplasmic component. Nitrate assimilation is inhibited by DNP, which probably affects the nitrite reduction step because neither nitrate reductase activity nor the transport of nitrate or nitrite is inhibited. On the other hand, DNP uptake is competitively inhibited by nitrate, probably at the transport level, because the nitroreductase activity is not inhibited in vitro by nitrate, nitrite, or ammonium. In addition, the decrease in the intracellular DNP concentration in the presence of nitrate probably inactivates the nitroreductase. These results allow prediction of a negative environmental effect if nitrate and DNP are released together to natural habitats, because it may lead to a lower rate of DNP metabolism and to nitrite accumulation.

Cyanide metabolism of Pseudomonas pseudoalcaligenes CECT5344: role of siderophores.

Cyanide is one of the most potent and toxic chemicals produced by industry. The jewelry industry of Córdoba (Spain) generates a wastewater (residue) that contains free cyanide, as well as large amounts of cyano-metal complexes. Cyanide is highly toxic to living systems because it forms very stable complexes with transition metals that are essential for protein function. In spite of its extreme toxicity, some organisms have acquired mechanisms to avoid cyanide poisoning. The biological assimilation of cyanide needs the concurrence of three separate processes: (i) a cyanide-insensitive respiratory chain, (ii) a system for iron acquisition (siderophores) and (iii) a cyanide assimilation pathway. Siderophores are low-molecular-mass compounds (600-1500 Da) that scavenge iron (Fe(3+)) ions (usually with extremely high affinity) from the environment under iron-limiting conditions. There are two main classes of siderophores: catechol and hydroxamate types. The catechol-type siderophores chelate ferric ion via a hydroxy group, whereas the hydroxamate-type siderophores bind iron via a carbonyl group with the adjacent nitrogen. In the presence of cyanide, bacterial proliferation requires this specific metal uptake system because siderophores are able to break down cyano-metal complexes. Pseudomonas pseudoalcaligenes CECT5344 is able to use free cyanide or cyano-metal complexes as nitrogen source. A proteomic approach was used for the isolation and identification, in this strain, of a protein that was induced in the presence of cyanide, namely CN0, that is involved in siderophore biosynthesis in response to cyanide. An overview of bacterial cyanide degradation pathways and the involvement of siderophores in this process are presented.

Alkaline cyanide biodegradation by Pseudomonas pseudoalcaligenes CECT5344.

Pseudomonas pseudoalcaligenes CECT5344 uses cyanide, cyanate, beta-cyanoalanine, and other cyanoderivatives as nitrogen sources under alkaline conditions, which prevents volatile HCN (pK(a) 9.2) formation. The cyanide consumed by this strain is stoichiometrically converted into ammonium. In addition, this bacterium grows with the heavy metal, cyanide-containing waste water generated by the jewellery industry, and is also a cyanide-resistant strain which induces an alternative oxidase and a siderophore-based mechanism for iron acquisition in the presence of cyanide. The detection of cyanase and beta-cyanoalanine nitrilase activities in cyanide-induced cells suggests their implication in the cyanide degradation pathway.

[Descriptive study of behavioural disorders in mild cognitive impairment]. / Estudio descriptivo de los trastornos conductuales en el deterioro cognitivo leve.

INTRODUCTION: Mild cognitive impairment (MCI) is defined as an abnormality in cognitive function not provoking a noticeable disability in activities of daily living in the affected person. In a group of patients with MCI, we propose to observe and to quantify the presence of behavioral disorders, using the neuropsychiatric inventory (NPI). PATIENTS AND METHODS: NPI is a known instrument in evaluation of this kind of disorders in patients with dementia, and it is a semi structured interview with a relevant informer or relative to the patient. NPI was applied to a series of 100 cases (61 women and 39 men) of MCI, diagnosed as usual in our settings. Mean age was 74.3 +/- 10 years, and mean MEC (Spanish modified version of MMSE) 25.57 +/- 4.2 (over a maximum of 35 points). RESULTS: Most prevalent disorder was depression, in 36 % of cases, and other frequent findings were irritability (35%), anxiety (24%) and apathy (19%). In some cases, agitation (4%), abnormal motor behavior (3%) and delusions (1%) were detected. Hallucination, disinhibition and euphoria or elation were not detected in this series. CONCLUSION: Data show a certain similarity with occidental culture environment, globally considered. The presence of behavioral and psychological disorders in patients with MCI could be a marker for later development of dementia. NPI can be a usable tool when detection and evaluation of these symptoms is required.

Estudio descriptivo de los trastornos conductuales en el deterioro cognitivo leve / Descriptive study of behavioural disorders in mild cognitive impairment

Introducción. El deterioro cognitivo leve (DCL) se define como una alteración de las funciones cognitivas que no motiva una disfunción notable en las actividades corrientes del afectado. En un grupo de pacientes con DCL nos proponemos observar y cuantificar la presencia de trastornos de la conducta, mediante el inventario neuropsiquiátrico (NPI). Pacientes y métodos. El NPI es un instrumento corriente en la evaluación de este tipo de trastornos en pacientes con demencia, consistente en una entrevista semiestructurada a un informador fiable del entorno del paciente. Se aplicó este instrumento a una serie de 100 pacientes (61 mujeres y 39 varones) diagnosticados de DCL en nuestra unidad. La edad media de la muestra fue de 74,3 ñ 10 años, y la puntuación media del MEC, 25,57 ñ 4,2. Resultados. En un 62 por ciento de los casos existía un trastorno conductual o psicológico. El trastorno más prevalente fue la depresión, en un 36 por ciento de los casos, seguido de irritabilidad (35 por ciento), ansiedad (24 por ciento) y apatía (19 por ciento). Presentes en algún caso, estuvieron la agitación (4 por ciento), la actividad motora aberrante (3 por ciento) y el delirio (sólo un caso). No se encontraron alucinaciones, desinhibición o euforia en este grupo de pacientes. Conclusión. Los datos encontrados coinciden en líneas generales con los descritos previamente para ámbitos de la cultura occidental en general. La existencia de trastornos conductuales y psicológicos en pacientes con DCL podría ser un factor predictivo del desarrollo ulterior de demencia.El NPI puede ser una herramienta útil en la detección y evaluación de estos trastornos (AU)

Introduction. Mild cognitive impairment (MCI) is defined as an abnormality in cognitive function not provoking a noticeable disability in activities of daily living in the affected person. In a group of patients with MCI, we propose to observe and to quantify the presence of behavioral disorders, using the neuropsychiatric inventory (NPI). Patients and methods. NPI is a known instrument in evaluation of this kind of disorders in patients with dementia, and it is a semi structured interview with a relevant informer or relative to the patient. NPI was applied to a series of 100 cases (61 women and 39 men) of MCI, diagnosed as usual in our settings. Mean age was 74.3 ± 10 years, and mean MEC (Spanish modified version of MMSE) 25.57 ± 4.2 (over a maximum of 35 points). Results. Most prevalent disorder was depression, in 36 % of cases, and other frequent findings were irritability (35%), anxiety (24%) and apathy (19%). In some cases, agitation (4%), abnormal motor behavior (3%) and delusions (1%) were detected. Hallucination, desinhibition and euphoria or elation were not detected in this series. Conclusion. Data show a certain similarity with occidental culture environment, globally considered. The presence of behavioral and psychological disorders in patients with MCI could be a marker for later development of dementia. NPI can be a usable tool when detection and evaluation of these symptoms is required (AU)

Flow-injection spectrophotometric determination of cyanate in bioremediation processes by use of immobilised inducible cyanase.

A new flow injection (FI) method for photometric monitoring of cyanate in bioremediation processes using immobilised native cyanase is described. The method is based on the catalytic reaction between cyanate and bicarbonate to produce ammonia and carbon dioxide in the presence of an inducible native cyanase, immobilised in a reactor packed with glass beads. Two degrees of purification of the biocatalyst were used-heated cell-free extract and purified extract of cyanase from Pseudomonas pseudoalcaligenes CECT 5344. The ammonia produced by the enzymatic reaction is finally monitored photometrically at 700 nm using a modification of the conventional Berthelot method. The method furnishes different calibration curves depending on the degree of purification of the cyanase, with linear ranges between 1.23 and 616.50 micromol L(-1) ( r(2)=0.9979, n=7) and between 1.07 and 308.25 micro mol L(-1) ( r(2)= 0.9992, n=7) for the heated cell-free extract and the purified cyanase extract, respectively. No statistically significant differences between the samples were found in the precision study evaluated at two cyanate concentration levels using one-way analysis of variance. A sampling frequency of 15 h(-1) was achieved. The method was used to monitor cyanate consumption in a cyanate bioremediation tank inoculated with Pseudomonas pseudoalcaligenes CECT 5344 strain. The correlation between cyanate degradation and ammonia production was tested using a conventional method. Finally, the method was applied to different samples collected from the bioremediation tank using the standard addition method; recoveries between 85.9 and 97.4% were obtained.

[Animal sting and bites]. / Picaduras y mordeduras de animales.

Under the heading of this subject we deal with stings by arthropods, making reference to the differences that exist between the stings of wasps and bees, commenting on the composition of the poisons and the different local and general reactions that are caused by such stings. Also discussed are the stings/bites caused by scorpions, spiders, ticks, and marine animals, with the clinical picture they provoke and the treatment that must be administered. Finally, snakebites are considered, with reference to the most frequent types of ophidia to be found in Navarra, how to differentiate between the bites of snakes and vipers, the different clinical pictures they provoke and the treatment to be applied

Picaduras y mordeduras de animales / Animal sting and bites

En este tema tratamos las picaduras por artrópodos. Se hace referencia a las diferencias que existen entre las picaduras de avispas y abejas, comentando la composición de venenos y las diferentes reacciones locales y generales que provocan dichas picaduras. Se exponen además las picaduras-mordeduras producidas por escorpiones, arañas, garrapatas, y animales marinos con la clínica que provocan y el tratamiento que es necesario administrar. Por último, se incluyen las mordeduras por serpientes, haciendo referencia a los tipos de ofidios más frecuentes en Navarra, la forma de diferenciar la mordedura de culebras de las víboras, la diferente clínica que provocan, y el tratamiento a aplicar (AU)