4,437 research outputs found

    Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay

    Get PDF
    Although delayed puberty is relatively common and often familial, its molecular and pathophysiologic basis is poorly understood. In contrast, the molecular mechanisms underlying some forms of hypogonadotropic hypogonadism (HH) are clearer, following the description of mutations in the genes KAL, GNRHR, and PROP1. Mutations in another gene, DAX1 (AHC), cause X-linked adrenal hypoplasia congenita and HH. Affected boys usually present with primary adrenal failure in infancy or childhood and HH at the expected time of puberty.DAX1 mutations have also been reported to occur with a wider spectrum of clinical presentations. These cases include female carriers of DAX1 mutations with marked pubertal delay and a male with incomplete BH and mild adrenal insufficiency in adulthood. Given this emerging phenotypic spectrum of clinical presentation in men and women with DAX1 mutations, we hypothesized that DAX1 might be a candidate gene for mutation in patients with idiopathic sporadic or familial HH or constitutional delay of puberty. Direct sequencing of DAX1 was performed in 106 patients, including 85 (80 men and 5 women) with sporadic HH or constitutional delay of puberty and patients from 21 kindreds with familial forms of these disorders. No DAX1 mutations were found in these groups of patients, although silent single nucleotide polymorphisms were identified (T114C, G498A). This study suggests that mutations in DAX1 are unlikely to be a common cause of HH or pubertal delay in the absence of a concomitant history of adrenal insufficiency

    A Study of Archiving Strategies in Multi-Objective PSO for Molecular Docking

    Get PDF
    Molecular docking is a complex optimization problem aimed at predicting the position of a ligand molecule in the active site of a receptor with the lowest binding energy. This problem can be formulated as a bi-objective optimization problem by minimizing the binding energy and the Root Mean Square Deviation (RMSD) difference in the coordinates of ligands. In this context, the SMPSO multi-objective swarm-intelligence algorithm has shown a remarkable performance. SMPSO is characterized by having an external archive used to store the non-dominated solutions and also as the basis of the leader selection strategy. In this paper, we analyze several SMPSO variants based on different archiving strategies in the scope of a benchmark of molecular docking instances. Our study reveals that the SMPSOhv, which uses an hypervolume contribution based archive, shows the overall best performance.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    Gyroid Optical Metamaterials: Calculating the Effective Permittivity of Multidomain Samples

    Get PDF
    Gold gyroid optical metamaterials are known to possess a reduced plasma frequency and linear dichroism imparted by their intricate subwavelength single gyroid morphology. The anisotropic optical properties are, however, only evident when a large individual gyroid domain is investigated. Multidomain gyroid metamaterials, fabricated using a polyisoprene-bb-polystyrene-bb-poly(ethylene oxide) triblock terpolymer and consisting of multiple small gyroid domains with random orientation and handedness, instead exhibit isotropic optical properties. Comparing three effective medium models, we here show that the specular reflectance spectra of such multidomain gyroid optical metamaterials can be accurately modeled over a broad range of incident angles by a Bruggeman effective medium consisting of a random wire array. This model accurately reproduces previously published results tracking the variation in normal incidence reflectance spectra of gold gyroid optical metamaterials as a function of host refractive index and volume fill fraction of gold. The effective permittivity derived from this theory confirms the change in sign of the real part of the permittivity in the visible spectral region (so, that gold gyroid metamaterials exhibit both dielectric and metallic behavior at optical wavelengths). That a Bruggeman effective medium can accurately model the experimental reflectance spectra implies that small multidomain gold gyroid optical metamaterials behave both qualitatively and quantitatively as an amorphous composite of gold and air (i.e., nanoporous gold) and that coherent electromagnetic contributions arising from the subwavelength gyroid symmetry are not dominant.This research was supported through the Swiss National Science Foundation through the National Center of Competence in Research Bio-Inspired Materials and grant numbers 200021_163220 (to U.S.) and PZ00P2_168223 (to B.D.W.), the Adolphe Merkle Foundation, the Engineering and Physical Sciences Research Council (EPSRC) through the Cambridge NanoDTC EP/G037221/1, EP/L027151/1, and EP/ G060649/1, and ERC LINASS 320503 and from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement no. 706329 (to I.G.). Y.G. and U.W. thank the National Science Foundation (DMR-1409105) for financial support

    The effect of fluid resuscitation on the effective circulating volume in patients undergoing liver surgery: a post-hoc analysis of a randomized controlled trial

    Get PDF
    To assess the significance of an analogue of the mean systemic filling pressure (Pmsa) and its derived variables, in providing a physiology based discrimination between responders and non-responders to fluid resuscitation during liver surgery. A post-hoc analysis of data from 30 patients undergoing major hepatic surgery was performed. Patients received 15 ml kg(-1) fluid in 30 min. Fluid responsiveness (FR) was defined as an increase of 20% or greater in cardiac index, measured by FloTrac-Vigileo((R)). Dynamic preload variables (pulse pressure variation and stroke volume variation: PPV, SVV) were recorded additionally. Pvr, the driving pressure for venous return (=Pmsa-central venous pressure) and heart performance (EH; Pvr/Pmsa) were calculated according to standard formula. Pmsa increased following fluid administration in responders (n = 18; from 13 +/- 3 to 17 +/- 4 mmHg, p < 0.01) and in non-responders (n = 12; from 14 +/- 4 to 17 +/- 4 mmHg, p < 0.01). Pvr, which was lower in responders before fluid administration (6 +/- 1 vs. 7 +/- 1 mmHg; p = 0.02), increased after fluid administration only in responders (from 6 +/- 1 to 8 +/- 1 mmHg; p < 0.01). EH only decreased in non-responders (from 0.56 +/- 0.17 to 0.45 +/- 0.12; p < 0.05). The area under the receiver operating characteristics curve of Pvr, PPV and SVV for predicting FR was 0.75, 0.73 and 0.72, respectively. Changes in Pmsa, Pvr and EH reflect changes in effective circulating volume and heart performance following fluid resuscitation, providing a physiologic discrimination between responders and non-responders. Also, Pvr predicts FR equivalently compared to PPV and SVV, and might therefore aid in predicting FR in case dynamic preload variables cannot be used

    Biological Stoichiometry in Human Cancer

    Get PDF
    A growing tumor in the body can be considered a complex ecological and evolutionary system. A new eco-evolutionary hypothesis (the "Growth Rate Hypothesis", GRH) proposes that tumors have elevated phosphorus (P) demands due to increased allocation to P-rich nucleic acids, especially ribosomal RNA, to meet the protein synthesis demands of accelerated proliferation.We determined the elemental (C, N, P) and nucleic acid contents of paired malignant and normal tissues from colon, lung, liver, or kidney for 121 patients. Consistent with the GRH, lung and colon tumors were significantly higher (by approximately two-fold) in P content (fraction of dry weight) and RNA content and lower in nitrogen (N):P ratio than paired normal tissue, and P in RNA contributed a significantly larger fraction of total biomass P in malignant relative to normal tissues. Furthermore, patient-specific differences for %P between malignant and normal tissues were positively correlated with such differences for %RNA, both for the overall data and within three of the four organ sites. However, significant differences in %P and %RNA between malignant and normal tissues were not seen in liver and kidney and, overall, RNA contributed only approximately 11% of total tissue P content.Data for lung and colon tumors provide support for the GRH in human cancer. The two-fold amplification of P content in colon and lung tumors may set the stage for potential P-limitation of their proliferation, as such differences often do for rapidly growing biota in ecosystems. However, data for kidney and liver do not support the GRH. To account for these conflicting observations, we suggest that local environments in some organs select for neoplastic cells bearing mutations increasing cell division rate ("r-selected," as in colon and lung) while conditions elsewhere may select for reduced mortality rate ("K-selected," as in liver and kidney)

    Impact of air pollution on cognitive impairment in older people: A cohort study in rural and suburban China

    Get PDF
    This is an accepted manuscript of a paper published by IOS Press on 13/10/2020, available online at: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200587 The accepted manuscript of the publication may differ from the final published version.Background: The impact of air pollution on cognitive impairment in older people has not been fully understood. It is unclear which air pollutants are the culprit. Objective: We assessed the associations of six air pollutants and air quality index (AQI) with cognitive impairment. Methods: We examined 7,311 participants aged ≥60 years from the ZJMPHS cohort in China. They were interviewed for baseline socio-demographic and disease risk factors in 2014, and re-interviewed in 2015 and 2016, respectively. The presence of cognitive impairment was determined by the Chinese version of the Mini-Mental State Examination. Daily area-level data monitored for air pollution during 2013-2015 was then examined for associations with cognitive impairment in logistic regression models. Results: Over the two years follow-up, 1,652 participants developed cognitive impairment, of which 917 were severe cases. Continuous air pollution data showed the risk of cognitive impairment increased with exposure to PM2.5 (fully adjusted odds ratio [aOR] 1.04, 95% CI 1.01-1.08), PM10 (1.03, 1.001-1.06), and SO2 (1.04, 1.01-1.08), but not with NO2, CO, O3, and AQI. Categorized data analysis for low, middle, and high level exposure demonstrated that the aOR increased with PM2.5 and AQI, somehow with PM10 and CO, but not significantly with SO2 and NO2, and decreased with O3. The patterns for these associations with severe cognitive impairment were stronger. Conclusion: Lowering PM2.5, PM10, SO2, and CO level could reduce the risk of cognitive impairment in older Chinese. Strategies to target most important air pollutants should be an integral component of cognitive interventions.Zhejiang Provincial Public Welfare Technology Application Research Project of China (LGF19H260003) and an EU grant from Horizon 2020 MSCA – DEMAIRPO #799247.Published versio

    Impact of air pollution on cognitive impairment in older people: A cohort study in rural and suburban China

    Get PDF
    © He et al. This is an accepted manuscript of a book chapter published by IOS Press. The definitive, peer reviewed and edited version of this Article is published in Calderón-Garcidueñas, L. (Ed.) Alzheimer’s Disease and Air Pollution, available online at: https://ebooks.iospress.nl/doi/10.3233/AIAD210021 The accepted version of the publication may differ from the final published version. For re-use please see the publisher's terms and conditions.Background: The impact of air pollution on cognitive impairment in older people has not been fully understood. It is unclear which air pollutants are the culprit. Objective: We assessed the associations of six air pollutants and air quality index (AQI) with cognitive impairment. Methods: We examined 7,311 participants aged ≥60 years from the ZJMPHS cohort in China. They were interviewed for baseline socio-demographic and disease risk factors in 2014, and re-interviewed in 2015 and 2016, respectively. The presence of cognitive impairment was determined by the Chinese version of the Mini-Mental State Examination. Daily area-level data monitored for air pollution during 2013-2015 was then examined for associations with cognitive impairment in logistic regression models. Results: Over the two years follow-up, 1,652 participants developed cognitive impairment, of which 917 were severe cases. Continuous air pollution data showed the risk of cognitive impairment increased with exposure to PM 2.5 (fully adjusted odds ratio [aOR] 1.04, 95%CI 1.01-1.08), PM 10 (1.03, 1.001-1.06), and SO 2 (1.04, 1.01-1.08), but not with NO 2, CO, O 3, and AQI. Categorized data analysis for low, middle, and high level exposure demonstrated that the aOR increased with PM 2.5 and AQI, somehow with PM 10 and CO, but not significantly with SO 2 and NO 2, and decreased with O 3. The patterns for these associations with severe cognitive impairment were stronger. Conclusion: Lowering PM 2.5, PM 10, SO 2, and CO level could reduce the risk of cognitive impairment in older Chinese. Strategies to target most important air pollutants should be an integral component of cognitive interventions.Published versio
    corecore