What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: the ESCARVAL-RISK study

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all cause mortality and hospitalization due to cardiovascular events in a high-risk population. Methods This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008±2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. Results 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/ HDL-Cholesterol: 8.94, 15.09, 6.92. Conclusions In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure

Gallstone ileus: management options and results on a series of 40 patients Íleo biliar: opciones terapéuticas y resultados en una serie de 40 casos

Introduction: controversy remains about the management of gallstone ileus. While some authors propose enterotomy, others defend the one-stage procedure (simultaneously fistula repair). The objective of the present study was to analyze management options and comparative study their results. Material and methods: retrospective and descriptive study with revision of clinical stories of patients with the diagnosis of gallstone ileus between 1987 and 2008. All the following variables were recorded: dates of hospital admission, surgery and discharge, age, sex, pathological antecedents, preoperative or intraoperative diagnosis, treatment, location of the fistula and location of the obstruction. End-result variables were: postoperative complications, mortality, complications during the follow-up and biliary complications. Results: a total of 40 patients were included of 46,648 admissions. Age, comorbidity, and intraoperative diagnosis were related with poorer short- and long-outcomes. The percentage of postoperative complications was similar for groups with and without fistula repair. Mortality was higher in the group with fistula repair (15vs. 25%). Biliary complications were more frequent in the group without fistula repair (11 vs. 0%). Sex, location of the fistula and location of the obstruction did not be related with the prognosis. Conclusion: one-stage procedure is related with higher mortality rate than enterotomy alone. Nevertheless, fistula repair reduces the number of biliary complications during the follow-up.<br>Introducción: todavía existe gran controversia sobre el mejor tratamiento del íleo biliar. Algunos autores proponen la enterotomía aislada, mientras otros defienden la reparación de la fístula bilioentérica en el mismo acto quirúrgico. El objetivo del presente estudio fue analizar las opciones terapéuticas en estos pacientes y estudiar sus resultados. Material y métodos: estudio retrospectivo y descriptivo, con revisión de las historias clínicas de los pacientes diagnosticados de íleo biliar desde 1987 hasta 2008. Se recogieron las fechas de ingreso, de intervención y del alta, edad, sexo, antecedentes patológicos, diagnóstico preoperatorio o intraoperatorio, tratamiento, lugar de la fístula y lugar de la obstrucción. Como variables de resultado se utilizaron las complicaciones postoperatorias, mortalidad, complicaciones en el seguimiento y complicaciones biliares. Resultados: se incluyeron 40 pacientes sobre 46.648 ingresos. La edad, la comorbilidad y el diagnóstico intraoperatorio se relacionaron con peores resultados a corto y largo plazo. El porcentaje de complicaciones postoperatorias fue similar para el grupo con abordaje de la fístula y para el grupo con enterotomía aislada. La mortalidad fue superior en el grupo con abordaje de la fístula (15 frente a 25%). Las complicaciones biliares fueron más frecuentes en el grupo sin abordaje de la fístula biliar (11 frente a 0%). El sexo, lugar de la fístula o el lugar de la obstrucción no demostraron diferencias. Conclusión: la cirugía en un solo tiempo se relaciona con mayor mortalidad que la enterotomía aislada. No obstante, añadir la reparación de la fístula reduce el número de complicaciones biliares en el seguimiento

Fluorescent Microarray for Multiplexed Quantification of Environmental Contaminants in Seawater Samples

The development of a fluorescent multiplexed microarray platform able to detect and quantify a wide variety of pollutants in seawater is reported. The microarray platform has been manufactured by spotting 6 different bioconjugate competitors and it uses a cocktail of 6 monoclonal or polyclonal antibodies raised against important families of chemical pollutants such as triazine biocide (i.e. Irgarol 1051®), sulfonamide and chloramphenicol antibiotics, polybrominated diphenyl ether flame-retardant (PBDE, i.e. BDE-47), hormone (17β-estradiol), and algae toxin (domoic acid). These contaminants were selected as model analytes, however, the platform developed has the potential to detect a broader group of compounds based on the cross-reactivity of the immunoreagents used. The microarray chip is able to simultaneously determine these families of contaminants directly in seawater samples reaching limits of detection close to the levels found in contaminated areas (Irgarol 1051® 0.19 ± 0,06 µg L−1; sulfapyridine, 0.17 ± 0.07 µg L−1; chloramphenicol, 0.11 ± 0.03 µg L−1; BDE-47, 2.71 ± 1.13 µg L−1; 17β-estradiol, 0.94 ± 0.30 µg L−1 and domoic acid, 1.71 ± 0.30 µg L−1). Performance of the multiplexed microarray chip was assessed by measuring 38 blind spiked seawater samples containing either one of these contaminants or mixtures of them. The accuracy found was very good and the coefficient of variation was < 20% in all the cases. No sample pre-treatment was necessary, and the results could be obtained in just 1 h 30 min. The microarray shows high sample throughput capabilities, being able to measure simultaneously more than 68 samples and screen them for a significant number of chemical contaminants of interest in environmental screening programs. © 2018 Elsevier B.V.This work has been funded by SEA-on-a-CHIP project (FP7-OCEAN-2013, n° 614168 ). The Nb4D group (formerly Applied Molecular Receptors group, AMRg) is a consolidated research group (Grup de Recerca) of the Generalitat de Catalunya and has support from the Departament d′Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya (expedient: 2014 SGR 1484). CIBER-BBN is an initiative funded by the Spanish National Plan for Scientific and Technical Research and Innovation 2013–2016, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The ICTS “NANOBIOSIS”, and particularly the Custom Antibody Service (CAbS, IQAC-CSIC, CIBER-BBN), is acknowledged for the assistance and support related to the immunoreagents used in this work. Appendix APeer reviewe