Bone Status in Patients with Phenylketonuria: A Systematic Review

Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Although dietary and, in some cases, pharmacological treatment has been successful in preventing intellectual disability in PKU patients who are treated early, suboptimal outcomes have been reported, including bone mineral disease. In this systematic review, we summarize the available evidence on bone health in PKU patients, including data on bone mineral density (BMD) and bone turnover marker data. Data from cohort and cross-sectional studies of children and adults (up to 40 years of age) were obtained by searching the MEDLINE and SCOPUS databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For each selected study, quality assessment was performed applying the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS I) tool. We found that mean BMD was lower in PKU patients than in reference groups, but was within the normal range in most patients when expressed as Z-score values. Furthermore, data revealed a trend towards an imbalance between bone formation and bone resorption, favoring bone removal. Data on serum levels of minerals and hormones involved in bone metabolism were very heterogeneous, and the analyses were inconclusive. Clinical trials that include the analysis of fracture rates, especially in older patients, are needed to gather more evidence on the clinical implications of lower BMD in PKU patients

Similarities between acylcarnitine profiles in large for gestational age newborns and obesity

Large for gestational age (LGA) newborns have an increased risk of obesity, insulin resistance, and metabolic syndrome. Acylcarnitine profiles in obese children and adults are characterized by increased levels of C3, C5, and certain medium-chain (C12) and long-chain (C14:1 and C16) acylcarnitines. C2 is also increased in insulin-resistant states. In this 1-year observational study of 2514 newborns (246 LGA newborns, 250 small for gestational age (GA) newborns, and 2018 appropriate for GA newborns), we analyzed and compared postnatal acylcarnitine profiles in LGA newborns with profiles described for obese individuals. Acylcarnitine analysis was performed by tandem mass spectrometry on dried-blood spots collected on day 3 of life. LGA newborns had higher levels of total short-chain acylcarnitines (p < 0.001), C2 (p < 0.01) and C3 (p < 0.001) acylcarnitines, and all C12, C14, and C16 acylcarnitines except C12:1. They also had a higher tendency towards carnitine insufficiency (p < 0.05) and carnitine deficiency (p < 0.001). No significant differences were observed between LGA newborns born to mothers with or without a history of gestational diabetes. This novel study describes a postnatal acylcarnitine profile in LGA with higher levels of C2, C3, total acylcarnitines, and total short-chain acylcarnitines that is characteristic of childhood and adult obesity and linked to an unhealthy metabolic phenotype.Dr Lopez has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 281854 -the ObERStress project, Xunta de Galicia (2015-CP079 and 2016-PG068), MINECO co-funded by FEDER (SAF2015-71026-R and BFU2015-70454-REDT/Adipoplast)S

Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves’ disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial

Background: Currently, both the American Thyroid Association and the European Thyroid Association recom mend preoperative preparation with Lugol's Solution (LS) for patients undergoing thyroidectomy for Graves’ Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to pro vide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidec tomy for GD. Methods: A multicenter randomized controlled trial will be performed. Patients ≥18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery. Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoper ative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS. Conclusions: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this set ting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations. Trial registration: ClinicalTrials.gov identifier: NCT03980132

Evaluation and perspective of 20 years of neonatal screening in Galicia: Program results

El Programa Gallego para la Detección Precoz de Enfermedades Endocrinas y Metabólicas se inició en 1978 y fue pionero en España en el cribado neonatal ampliado con la incorporación de la espectrometría de masas en julio de 2000. Como objetivo primario se criban veintiocho enfermedades, incluyendo las de la cartera básica del Servicio Nacional de Salud excepto la anemia de células falciformes, que está en fase de inclusión. En sus veinte años de trayectoria se analizaron 404.616 recién nacidos (RN), identificando 547 casos afectos de las enfermedades incluidas, con una incidencia global de 1:739 RN vivos y de 1:1.237 RN de las enfermedades metabólicas congénitas (EMC) cribadas (1:1.580 RN excluyendo la hiperfenilalaninemia benigna-HPA), con una participación media del 99,35%, progresivamente creciente durante el período analizado. Entre las patologías cribadas destacan por su incidencia el hipotirodismo congénito (1:2.211 RN), la cistinuria (1:4.129 RN) y la HPA (1:5.699 RN), seguida de fenilcetonuria y fibrosis quística (1:10.936 RN). Se identificaron sesenta y seis casos de falsos positivos (diecisiete de los mismos en relación con patología materna) y cinco falsos negativos, siendo el VPP (valor predictivo positivo) y el VPN (valor predictivo negativo) global del programa del 89,2% y 99,99%, respectivamente, con una sensibilidad de 99,09% y una especificidad del 99,98%. La tasa de mortalidad de los pacientes con EMC diagnosticados fue del 1,52%, presentando once casos sintomatología previa al resultado del cribado (2%). El cociente intelectual de los pacientes con EMC y riesgo de afectación neurológica es normal en más del 95% de los casosGalician newborn screening program for early detection of endocrine and metabolic diseases began in 1978 and was a pioneer in expanded newborn screening in Spain with the incorporation of mass spectrometry in July 2000. As a primary objective, 28 diseases are screened, including those recommended SNS except sickle cell anemia which is in the inclusion phase. In its 20-year history, 404,616 newborns (nb) have been analyzed, identifying 547 cases affected by the diseases included, with a global incidence of 1: 739 newborns and 1: 1.237 of the screened inborn errors of metabolism (IEM) (1:1.580 nb if excluding benign hyperphenylalaninemia-HPA), with an average participation of 99.35%, progressively higher during the analyzed period. Among the pathologies screened, congenital hypothyroidism (1:2.211 nb), cystinuria (1:4.129 nb) and HPA (1:5.699 nb), followed by phenylketonuria and cystic fibrosis (1:10,936 nb) stand out for their incidence. Sixty-six cases of false positives were identified (seventeen of them in relation to maternal pathology) and five false negatives, being the overall PPV and NPV of the program respectively of 89.2% and 99.99%, with a sensitivity of 99.09% and a specificity of 99.98%. The mortality rate of diagnosed CME patients is 1.52%, with eleven cases presenting symptoms prior to the screening result (2%). The intelligence quotient of IEM patients at risk of neurological involvement is normal in more than 95% of casesS

A morphological study of galaxies in ZwCl0024+1652, a galaxy cluster at redshift z ∼ 0.4

ABSTRACT: he well-known cluster of galaxies ZwCl0024+1652 at z ∼ 0.4 lacks an in-depth morphological classification of its central region. While previous studies provide a visual classification of a patched area, we used the public code called galaxy Support Vector Machine GALSVM) and HST/ACS data as well as the WFP2 master catalogue to automatically classify all cluster members up to 1 Mpc. GALSVM analyses galaxy morphologies through support vector machine (SVM). From the 231 cluster galaxies, we classified 97 as early types (ETs) and 83 as late types (LTs). The remaining 51 stayed unclassified (or undecided). By cross-matching our results with the existing visual classification, we found an agreement of 81 per cent. In addition to previous Zwcl0024 morphological classifications, 121 of our galaxies were classified for the first time in this work. In addition, we tested the location of classified galaxies on the standard morphological diagrams, colour–colour and colour–magnitude diagrams. Out of all cluster members, ∼20 per cent are emission-line galaxies, taking into account previous GLACE results. We have verified that the ET fraction is slightly higher near the cluster core and decreases with the clustercentric distance, while the opposite trend has been observed for LT galaxies. We found a higher fraction of ETs (54 per cent) than LTs (46 per cent) throughout the analysed central region, as expected. In addition, we analysed the correlation between the five morphological parameters (Abraham concentration, Bershady–Concelice concentration, asymmetry, Gini, and M20 moment of light) and the clustercentric distance, without finding a clear trend. Finally, as a result of our work, the morphological catalogue of 231 galaxies containing all the measured parameters and the final classification is available in the electronic form of this paper.MP also acknowledges support from the Spanish MINECO under projects AYA2013-42227-P and AYA2016-76682-C3-1-P- This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) under the grants AYA2014-58861-C3-2-P, AYA2014-58861-C3-3-P, AYA2017-88007-C3-1-P, and AYA2017-88007-C3-2-P

Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Withdrawal Is Associated with Higher Mortality in Hospitalized Patients with COVID-19

Our main aim was to describe the effect on the severity of ACEI (angiotensin-converting enzyme inhibitor) and ARB (angiotensin II receptor blocker) during COVID-19 hospitalization. A retrospective, observational, multicenter study evaluating hospitalized patients with COVID-19 treated with ACEI/ARB. The primary endpoint was the incidence of the composite outcome of prognosis (IMV (invasive mechanical ventilation), NIMV (non-invasive mechanical ventilation), ICU admission (intensive care unit), and/or all-cause mortality). We evaluated both outcomes in patients whose treatment with ACEI/ARB was continued or withdrawn. Between February and June 2020, 11,205 patients were included, mean age 67 years (SD = 16.3) and 43.1% female; 2162 patients received ACEI/ARB treatment. ACEI/ARB treatment showed lower all-cause mortality (p < 0.0001). Hypertensive patients in the ACEI/ARB group had better results in IMV, ICU admission, and the composite outcome of prognosis (p < 0.0001 for all). No differences were found in the incidence of major adverse cardiovascular events. Patients previously treated with ACEI/ARB continuing treatment during hospitalization had a lower incidence of the composite outcome of prognosis than those whose treatment was withdrawn (RR 0.67, 95%CI 0.63-0.76). ARB was associated with better survival than ACEI (HR 0.77, 95%CI 0.62-0.96). ACEI/ARB treatment during COVID-19 hospitalization was associated with protection on mortality. The benefits were greater in hypertensive, those who continue

Galaxy classification: deep learning on the OTELO and COSMOS databases

Context. The accurate classification of hundreds of thousands of galaxies observed in modern deep surveys is imperative if we want to understand the universe and its evolution. Aims. Here, we report the use of machine learning techniques to classify early- and late-type galaxies in the OTELO and COSMOS databases using optical and infrared photometry and available shape parameters: either the Sersic index or the concentration index. Methods. We used three classification methods for the OTELO database: 1) u-r color separation , 2) linear discriminant analysis using u-r and a shape parameter classification, and 3) a deep neural network using the r magnitude, several colors, and a shape parameter. We analyzed the performance of each method by sample bootstrapping and tested the performance of our neural network architecture using COSMOS data. Results. The accuracy achieved by the deep neural network is greater than that of the other classification methods, and it can also operate with missing data. Our neural network architecture is able to classify both OTELO and COSMOS datasets regardless of small differences in the photometric bands used in each catalog. Conclusions. In this study we show that the use of deep neural networks is a robust method to mine the cataloged dataComment: 20 pages, 10 tables, 14 figures, Astronomy and Astrophysics (in press

Reformas agrarias y reparto de la tierra. Análisis critico del sistema vigente y eventual propuesta de solución de un problema actual a partir de sus raíces romanas

La idea central del proyecto es estudiar el régimen de propiedad de la tierra. Cómo se inicia, a partir del momento en que el hombre muta de nómade en sedentario, atravesando desde entonces una serie de sistemas que sucesivamente van siendo superados por otros que se demuestran más eficaces o, al menos, más acordes a las necesidades sociales del momento: Propiedad colectiva, propiedad familiar, propiedad individual. Aquí se inserta el derecho romano, que supo por dolorosa experiencia plasmada en cruentos conflictos sociales, implementar finalmente una suerte de reforma agraria basada en el consenso, que se instrumentó bajo la forma del derecho real de enfiteusis. No hubo expropiación, pero se permitió al trabajador rural tener importantes derechos sobre el suelo que laboraba, y sobre los frutos de esa labor. Este derecho real, admitido en muchas legislaciones modernas, no tiene cabida en Argentina la cual optó por la muy discutible experiencia de suprimirlo, a raíz de una desventurada experiencia histórica. ¿Será posible reintroducirlo, con una modalidad más acorde al precedente romano? ¿Tendrá utilidad para coadyuvar a paliar un agudo problema social en otros países hermanos de América? Si eso fuere así, nuestra idea es proponer una reforma legal, que pueda ser útil a nuestros legisladores. Con lo cual se lograría integrar e internalizar la experiencia romana, para intentar discernir si ella puede ser de provecho aún hoyFil: Ghirardi, Juan Carlos. Universidad Católica de Córdoba. Facultad de Derecho y Ciencias Sociales; ArgentinaFil: Filippi, María Cristina. Universidad Católica de Córdoba. Facultad de Derecho y Ciencias Sociales; Argentin

Reformas agrarias y reparto de la tierra. Análisis critico del sistema vigente y eventual propuesta de solución de un problema actual a partir de sus raíces romanas

La idea central del proyecto es estudiar el régimen de propiedad de la tierra. Cómo se inicia, a partir del momento en que el hombre muta de nómade en sedentario, atravesando desde entonces una serie de sistemas que sucesivamente van siendo superados por otros que se demuestran más eficaces o, al menos, más acordes a las necesidades sociales del momento: Propiedad colectiva, propiedad familiar, propiedad individual. Aquí se inserta el derecho romano, que supo por dolorosa experiencia plasmada en cruentos conflictos sociales, implementar finalmente una suerte de reforma agraria basada en el consenso, que se instrumentó bajo la forma del derecho real de enfiteusis. No hubo expropiación, pero se permitió al trabajador rural tener importantes derechos sobre el suelo que laboraba, y sobre los frutos de esa labor. Este derecho real, admitido en muchas legislaciones modernas, no tiene cabida en Argentina la cual optó por la muy discutible experiencia de suprimirlo, a raíz de una desventurada experiencia histórica. ¿Será posible reintroducirlo, con una modalidad más acorde al precedente romano? ¿Tendrá utilidad para coadyuvar a paliar un agudo problema social en otros países hermanos de América? Si eso fuere así, nuestra idea es proponer una reforma legal, que pueda ser útil a nuestros legisladores. Con lo cual se lograría integrar e internalizar la experiencia romana, para intentar discernir si ella puede ser de provecho aún hoyFil: Ghirardi, Juan Carlos. Universidad Católica de Córdoba. Facultad de Derecho y Ciencias Sociales; ArgentinaFil: Filippi, María Cristina. Universidad Católica de Córdoba. Facultad de Derecho y Ciencias Sociales; Argentin

The OTELO survey. A case study of [O III]4959,5007 emitters at <z> = 0.83

The OTELO survey is a very deep, blind exploration of a selected region of the Extended Groth Strip and is designed for finding emission-line sources (ELSs). The survey design, observations, data reduction, astrometry, and photometry, as well as the correlation with ancillary data used to obtain a final catalogue, including photo-z estimates and a preliminary selection of ELS, were described in a previous contribution. Here, we aim to determine the main properties and luminosity function (LF) of the [O III] ELS sample of OTELO as a scientific demonstration of its capabilities, advantages, and complementarity with respect to other surveys. The selection and analysis procedures of ELS candidates obtained using tunable filter (TF) pseudo-spectra are described. We performed simulations in the parameter space of the survey to obtain emission-line detection probabilities. Relevant characteristics of [O III] emitters and the LF([O III]), including the main selection biases and uncertainties, are presented. A total of 184 sources were confirmed as [O III] emitters at a mean redshift z=0.83. The minimum detectable line flux and equivalent width (EW) in this ELS sample are $\sim$5 $\times$ 10$^{-19}$ erg s$^{-1}$ cm$^{2}$ and $\sim$6 \AA, respectively. We are able to constrain the faint-end slope ($\alpha = -1.03\pm0.08$) of the observed LF([O III]) at z=0.83. This LF reaches values that are approximately ten times lower than those from other surveys. The vast majority (84\%) of the morphologically classified [O III] ELSs are disc-like sources, and 87\% of this sample is comprised of galaxies with stellar masses of M$_\star$ $<$ 10$^{10}$ M$_{\odot}$.Comment: v1: 16 pages, 6 figures. Accepted in Astronomy \& Astrophysics. v2: Author added in metadat