Interstellar detection of O-protonated carbonyl sulfide, HOCS+

We present the first detection in space of O-protonated carbonyl sulfide (\ch{HOCS+}), in the midst of an ultradeep molecular line survey toward the G+0.693-0.027 molecular cloud. From the observation of all $K$$_a$ = 0 transitions ranging from $J$$_{lo}$ = 2 to $J$$_{lo}$ = 13 of \ch{HOCS+} covered by our survey, we derive a column density of $N$ = (9 $\pm$ 2)$\times$10$^{12}$ cm$^{-2}$, translating into a fractional abundance relative to H$_2$ of $\sim$7$\times$10$^{-11}$. Conversely, the S-protonated \ch{HSCO+} isomer remains undetected, and we derive an upper limit to its abundance with respect to H$_2$ of $\leq$3$\times$10$^{-11}$, a factor of $\geq$2.3 less abundant than \ch{HOCS+}. We obtain a \ch{HOCS+}/OCS ratio of $\sim$2.5$\times$10$^{-3}$, in good agreement with the prediction of astrochemical models. These models show that one of the main chemical routes to the interstellar formation of \ch{HOCS+} is likely the protonation of OCS, which appears to be more efficient at the oxygen end. Also, we find that high values of cosmic-ray ionisation rates (10$^{-15}$-10$^{-14}$ s$^{-1}$) are needed to reproduce the observed abundance of \ch{HOCS+}. In addition, we compare the O/S ratio across different interstellar environments. G+0.693-0.027 appears as the source with the lowest O/S ratio. We find a \ch{HOCO+}/\ch{HOCS+} ratio of $\sim$31, in accordance with other O/S molecular pairs detected toward this region and also close to the O/S solar value ($\sim$37). This fact indicates that S is not significantly depleted within this cloud due to the action of large-scale shocks, unlike in other sources where S-bearing species remain trapped on icy dust grains.Comment: Forthcoming paper in The Astrophysical Journal (in press

Discovery of the elusive carbonic acid (HOCOOH) in space

After a quarter century since the detection of the last interstellar carboxylic acid, acetic acid (CH$_3$COOH), we report the discovery of a new one, the cis-trans form of carbonic acid (HOCOOH), toward the Galactic Center molecular cloud G+0.693-0.027. HOCOOH stands as the first interstellar molecule containing three oxygen atoms and also the third carboxylic acid detected so far in the interstellar medium. Albeit the limited available laboratory measurements (up to 65 GHz), we have also identified several pairs of unblended lines directly in the astronomical data (between 75-120 GHz), which allowed us to slightly improve the set of spectroscopic constants. We derive a column density for cis-trans HOCOOH of $N$ = (6.4 $\pm$ 0.4) $\times$ 10$^{12}$ cm$^{-2}$, which yields an abundance with respect to molecular H$_2$ of 4.7 $\times$ 10$^{-11}$. Meanwhile, the extremely low dipole moment (about fifteen times lower) of the lower-energy conformer, cis-cis HOCOOH, precludes its detection. We obtain an upper limit to its abundance with respect to H$_2$ of $\leq$ 1.2 $\times$10$^{-9}$, which suggests that cis-cis HOCOOH might be fairly abundant in interstellar space, although it is nearly undetectable by radio astronomical observations. We derive a cis-cis/cis-trans ratio $\leq$ 25, consistent with the smaller energy difference between both conformers compared with the relative stability of trans- and cis-formic acid (HCOOH). Finally, we compare the abundance of these acids in different astronomical environments, further suggesting a relationship between the chemical content found in the interstellar medium and the chemical composition of the minor bodies of the Solar System, which could be inherited during the star formation process.Comment: Accepted for publication in The Astrophysical Journa

First glycine isomer detected in the interstellar medium: glycolamide (NH2_2C(O)CH2_2OH)

We report the first detection in the interstellar medium of a C$_2$H$_5$O$_2$N isomer: $syn$-glycolamide (NH$_2$C(O)CH$_2$OH). The exquisite sensitivity at sub-mK levels of an ultra-deep spectral survey carried out with the Yebes 40m and IRAM 30m telescopes towards the G+0.693-0.027 molecular cloud have allowed us to unambiguously identify multiple transitions of this species. We derived a column density of (7.4 $\pm$ 0.7)$\times$10$^{12}$ cm$^{-2}$, which implies a molecular abundance with respect to H$_2$ of 5.5$\times$10$^{-11}$. The other C$_2$H$_5$O$_2$N isomers, including the higher-energy $anti$ conformer of glycolamide, and two conformers of glycine, were not detected. The upper limit derived for the abundance of glycine indicates that this amino acid is surely less abundant than its isomer glycolamide in the ISM. The abundances of the C$_2$H$_5$O$_2$N isomers cannot be explained in terms of thermodynamic equilibrium, and thus chemical kinetics need to be invoked. While the low abundance of glycine might not be surprising, based on the relative low abundances of acids in the ISM compared to other compounds (e.g. alcohols, aldehydes or amines), several chemical pathways can favour the formation of its isomer glycolamide. It can be formed through radical-radical reactions on the surface of dust grains. The abundances of these radicals can be significantly boosted in an environment affected by a strong ultraviolet field induced by cosmic rays, such as that expected in G+0.693-0.027. Therefore, as shown by several recent molecular detections towards this molecular cloud, it stands out as the best target to discover new species with carbon, oxygen and nitrogen with increasing chemical complexity.Comment: Accepted in The Astrophysical Journal Letter

Precursors of the RNA-world in space: Detection of (ZZ)-1,2-ethenediol in the interstellar medium, a key intermediate in sugar formation

We present the first detection of ($Z$)-1,2-ethenediol, (CHOH)$_2$, the enol form of glycolaldehyde, in the interstellar medium towards the G+0.693-0.027 molecular cloud located in the Galactic Center. We have derived a column density of (1.8$\pm$0.1)$\times$10$^{13}$ cm$^{-2}$, which translates into a molecular abundance with respect to molecular hydrogen of 1.3$\times$10$^{-10}$. The abundance ratio between glycolaldehyde and ($Z$)-1,2-ethenediol is $\sim$5.2. We discuss several viable formation routes through chemical reactions from precursors such as HCO, H$_2$CO, CHOH or CH$_2$CHOH. We also propose that this species might be an important precursor in the formation of glyceraldehyde (HOCH$_2$CHOHCHO) in the interstellar medium through combination with the hydroxymethylene (CHOH) radical.Comment: Accepted for publication in The Astrophysical Journal Letter

GDF-15 is elevated in children with mitochondrial diseases and is induced by mitochondrial dysfunction

Background We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction. Methods We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA. Results Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3% (81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated lev- els of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated. Conclusions Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochon- drial dysfunction and that its levels correlate in vitro with FGF-21 level

Hypertension in the very old; prevalence, awareness, treatment and control: a cross-sectional population-based study in a Spanish municipality

<p>Abstract</p> <p>Background</p> <p>Information on hypertension in the very elderly is sparse. Until recently evidence of benefits from pharmacological treatment was inconclusive. We estimated the prevalence of hypertension in subjects aged 80 or more, the proportion of awareness, treatment and control. Explanatory variables associated with good control were also studied.</p> <p>Methods</p> <p>Cross sectional, population-based study, conducted in Martorell, an urban Spanish municipality, in 2005. By simple random sampling from the census, 323 subjects aged 80 or more were included. Patients were visited at home or in the geriatric institution and after giving informed consent, the study variables were collected. These included: supine and standing blood pressure and information about diagnosis and treatment of hypertension. The estimation and 95% confidence interval were obtained and a logistic regression model was used to study explanatory variables associated with blood pressure below 140/90 mm Hg.</p> <p>Results</p> <p>The prevalence of hypertension was 72.8% (95%CI: 69.5 – 76.6%) and 93% of the patients were aware of this condition, of whom 96.3% (95%CI: 93.65 – 97.9%) had been prescribed pharmacological treatment and 30.7% (95%CI: 25.8 – 36.1%) had blood pressure below 140/90 mm Hg. Some of the patients (43%) had one antihypertensive drug and 39.5% had two in combination. Explanatory variables associated with blood pressure below 140/90 mm Hg included prescription of a diuretic, OR: 0.31 (95%CI: 0.14 – 0.66), and history of ischemic heart disease, OR: 0.21 (95%CI: 0.1 – 0.47).</p> <p>Conclusion</p> <p>The prevalence of hypertension in population aged 80 or more was over 70%. Most patients were aware of this condition and they had antihypertensive medication prescribed. Approximately one third of treated patients had blood pressure below 140/90 mm Hg. Patients with heart disease and with diuretics had more frequently blood pressure below this value.</p

Pharmacist role in the nutrition area at the European level

Una vez licenciado, el farmacéutico puede optar por un elevado número de salidas profesionales, tanto en el sector público al servicio de los diferentes cuerpos y administraciones, como en el sector privado. Los perfiles profesionales más frecuentes del farmacéutico pueden englobarse en 4 modalidades: Oficina de Farmacia (Farmacia Comunitaria), Farmacia Hospitalaria, Distribución e Industria Farmacéutica o Análisis y Salud Pública. A nivel de oficina de farmacia, el farmacéutico, junto a la dispensación de medicamentos, ejerce un destacado papel como asesor y consejero de salud. Las estadísticas desvelan que una de cada cuatro personas que entran en una farmacia no adquiere medicamentos, sino que sólo pide un consejo sanitario, incluyendo asesoría sobre dietas, alimentación y nutrición. Además, la aparición en los últimos años de complementos alimenticios, de venta en farmacia, hace que el farmacéutico deba formarse y comportarse como profesional en lo que respecta a temas de nutrición. Otra salida profesional, como la inspección Farmacéutica, incluye la supervisión de agua y alimentos no animales, por lo que el farmacéutico debe tener un amplio conocimiento sobre la legislación, sanidad y análisis de alimentos. Por otro lado, la industria farmacéutica incluye una amplia variedad de salidas profesionales, incluyéndose dirección técnica, control de calidad y de fabricación, gestión comercial, documentación científica o análisis. La industria agroalimentaria ha experimentado importantes cambios en las últimas décadas, exigiendo profesionales en la materia, como dietistas o analistas bromatológicos, dentro de un equipo multidisciplinar. En este sentido, el farmacéutico, a través del nuevo grado en Farmacia, debe adquirir una base sólida en el campo de la nutrición y bromatología. Así, las competencias recogidas en la Orden CIN/2137/2008 ponen de manifiesto la importancia de la formación del futuro farmacéutico en el ámbito de la alimentación.Once graduated, the pharmacist can choose a high number of professional skills, both in public and private sectors. The most frequent professional skills of the pharmacist can be included in 4 different fields: Pharmacy Office (Communitary Pharmacy), Hospital Pharmacy, Distribution and Pharmaceutical Industry or Analysis and Public Health. At the pharmacy office level, the pharmacist, along with the medicines dispensation, exercises an out-standing role as health adviser. The statistics reveal that 25% of the pharmacy customers do not acquire medicines, but they only ask for a sanitary advice, including nutrition and dietetic consultations. Moreover, in the last years nutritive supplements have been included within the pharmaceutical sales. Thus, the pharmacist should be formed about nutritional topics. Another professional skill, like the pharmaceutical inspection, includes drinkable water and non-animal foodstuffs analyses. Then, the pharmacist should have a wide knowledge on legislation, health and food analysis. On the other hand, the pharmaceutical industry includes a wide variety of professional skills, including technical direction, quality control, commercial management, scientific documentation or analysis. Finally, the agro-alimentary industry has experienced important changes in the last decades, demanding professionals in the matter, like dietitians or food analysts. In this sense, the pharmacist, across the new degree in Pharmacy, must acquire a solid base in the nutrition and bromatology field. Therefore, the competences gathered in the Disposition CIN / 2137/2008 reveals the importance of the formation of the future pharmacist in the nutrition area

The new degree in pharmacy. Is it enough for the formative needs in the nutrition area?

La importancia de la alimentación en la consecución de la salud y en la prevención de la enfermedad y la necesidad de un buen control de la dieta para alcanzar resultados satisfactorios en la reducción del riesgo, tratamiento y control de muchas de las enfermedades crónicas, es un hecho documentado científicamente y de gran relevancia en la sociedad actual. La Orden CIN/2137/2008, de 3 de julio establece los requisitos para la verificación de los títulos universitarios oficiales que habiliten para el ejercicio de la profesión farmacéutica, abarcando diversas competencias que aluden directamente a la formación del farmacéutico en el campo de la nutrición. Entre ellas se incluyen 1) Prestar consejo terapéutico en farmacoterapia y dietoterapia, así como consejo nutricional y alimentario a los usuarios de los establecimientos en los que presten servicio. 2) Conocer la relación existente entre la alimentación y salud, y la importancia de la dieta en el tratamiento y prevención de las enfermedades. 3) Desarrollar análisis higiénico-sanitarios (bioquímico, bromatológico, microbiológicos, parasitológicos) relacionados con la salud en general y con los alimentos y medio ambiente en particular. 4) Conocer las técnicas analíticas relacionadas con el diagnóstico de laboratorio de tóxicos, alimentos y medioambiente. En este sentido, el nuevo Grado en Farmacia aprobado por el Consejo de Gobierno de la Universidad de Granada incluye la asignatura troncal “Nutrición y Bromatología” de 6 créditos. Sin embargo los créditos obligatorios aprobados por la ANECA para esta materia en 8 Universidades Españolas oscilan entre 7,5 para Sevilla y 12 créditos para Madrid con una media de 9,4 créditos. De esta forma ¿Es posible cubrir con los 6 créditos asignados a esta materia una formación mínima para que el farmacéutico pueda realizar adecuadamente las competencias que se le han asignado?The importance of nutrition on human health and on illness prevention, and the need for a good control of the diet to reach satisfactory results in the reduction of the risk, treatment and control of many of the chronic diseases, is a scientifically documented fact quite relevant in the current society. The Disposition CIN

Evolution of the Maillard Reaction in Glutamine or Arginine-Dextrinomaltose Model Systems

Enteral formulas are foods designed for medical uses to feed patients who are unable to eat normally. They are prepared by mixing proteins, amino acids, carbohydrates and fats and submitted to sterilization. During thermal treatment, the Maillard reaction takes place through the reaction of animo acids with reducing sugars. Thus, although glutamine and arginine are usually added to improve the nutritional value of enteral formulas, their final concentration may vary. Thus, in the present paper the early, intermediate, and advanced states of the Maillard reaction were studied in model systems by measuring loss of free amino acids through the decrease of fluorescence intensity with o-phtaldialdehyde (OPA), 5-Hydroximethylfurfural (HMF), furfural, glucosylisomaltol, fluorescence, and absorbance at 420 nm. The systems were prepared by mixing glutamine or arginine with dextrinomaltose (similar ingredients to those used in special enteral formula), and heated at 100 °C, 120 °C and 140 °C for 0 to 30 min. The recorded changes in the concentration of furanic compounds was only useful for longer heating times of high temperatures, while absorbance and fluorescence measurements were useful in all the assayed conditions. In addition, easiness and sensitivity of absorbance and fluorescence make them useful techniques that could be implemented as indicators for monitoring the manufacture of special enteral formulas. Glucosylisomaltol is a useful indicator to monitor the manufacture of glutamine-enriched enteral formulas