Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Hidrólisis del Ion V(III) a pH mayores de 3 en KCl 3M a 25 °C

Se estudio la hidrólisis del ion Vanadio (III) por medio de medidas de fem (H) a 25 ºC en KCl 3,0 M (M = mol/ dm3) como medio iónico, para un rango de concentración total de Vanadio (III) entre 8 y 31,5 mM a pH mayores de 3. El análisis de los datos potenciométricos realizado mediante el programa computacional de mínimos cuadrados generalizados LETAGROP, indica la formación de las siguientes hidroxoespecies y constantes de estabilidad (-log ßpq): VOH2+ (3,13 ± 0,08), V2(OH)24+ (3,76 ± 0,06), V(OH)2+ (6,86 ± 0,02) y V3(OH)8+ (27,47 ± 0,04).51-56cuatrimestreVanadium (III) ion Hydrolysis at pH higher than 3 in KCl 3M at 25 °C. The Vanadium (III) hydrolysis has been studied at 25 ºC in 3.0 M KCl as ionic medium for a range of total Vanadium concentration between 8 and 31,5 mM at pH higher than 3. The analysis of the potentiometric data by means of least-squares computational program LETAGROP, indicated the formation of the following hydroxospecies and their stability constants (-log ßpq): VOH2+ (3.13 ± 0.08), V2(OH)24+ (3.76 ± 0.06), V(OH)2+ (6.86 ± 0.02), and V3(OH)8+ (27.47 ± 0.04)

Embarazo molar tubárico. Reporte de un caso

La mola hidatiforme, es una afecci&oacute;n de las vellosidades coriales, que se caracteriza desde el punto de vista histol&oacute;gico por presentar proliferaci&oacute;n del trofoblasto, edema y agrandamiento de las vellosidades coriales y desaparici&oacute;n del &aacute;rbol vascular

Estudio de la hidrólisis del ion Niquel(II) y de la formación de los complejos de Niquel(II) con los ácidos Picolínico y Dipicolínico en NaCl 1,0 mol.dm-3 a 25°C

Estudio de la hidrólisis del ion Niquel(II) y de la formación de los complejos de Niquel(II) con los ácidos Picolínico y Dipicolínico en NaCl 1,0 mol.dm-3 a 25°[email protected] productos de hidrólisis (formación de compuestos hidroxilados) del ion Níquel(II) y de las especies complejas formadas entre el Ni(II) y los ligandos ácido picolínico (Hpic) y ácido dipicolínico (H2dipic), se han estudiado potenciométricamente en solución acuosa (a 25ºC, en medio iónico de NaCl I = 1,0 mol.dm-3). En la aplicación del programa informático de mínimos cuadrados generalizados, LETAGROP, a la data experimental de fem(H), se observó la formación de los productos de hidrólisis [Ni(OH)]+, [Ni(OH)2] y [Ni4(OH)4]4-. Adicionalmente, se ha detectado la formación de los complejos [Ni(pic)]+, [Ni(pic)2] y [Ni(pic)3]- con ácido picolínico y de las especies [Ni(dipic)] y [Ni(dipic)2]2- con ácido dipicolínico. Las constantes de estabilidad de los complejos formados fueron determinadas por mediciones potenciométricas

Potentiometric determination of stability constants for ternary Vanadium(III) complexes with dipicolinic acid and the amino acids serine, threonine, methionine and phenylalanine/ Determinación potenciométrica de constantes de estabilidad para complejos de

In this work, we present the results of the speciation of the ternary complexes formed between vanadium(III), dipicolinic acid (H2Dipic) and the amino acids serine (Ser, HL), threonine (Thr, HL), methionine (Met, HL) and phenylalanine (Phe, HL), in aqueous solution at 25.0(1)&deg;C using 3.0 mol.dm-3 KCl as the ionic medium. The analysis of the potentiometric data using the least squares computational program LETAGROP, indicates the formation of the species [V(Dipic)(HL)]+, V(Dipic)(L), [V(Dipic)(L)(OH)]- and [V(Dipic)(L)(OH)2]2-, in the ternary V(III)-H2Dipic-Amino acids (HL) systems studied. The values of &Delta; log K&rsquo;&rsquo; for ternary systems involving amino acids have been evaluated and discussed. The species distribution diagrams as a function of pH were briefly discussed. The spectrophotometric spectra were done in order to get a qualitative characterization of the complexes formed in aqueous solution, indicates that the dipicolinate is acting as a tridentade ligand and the complexes formed are all heptacoordinated

Ternary complex formation between vanadium(III)–salicylic acid and histidine, cysteine, aspartic and glutamic acids as a basis to obtain new antidiabetic agents

En el presente trabajo se estudi&oacute; los equilibrios en soluci&oacute;n de los complejos ternarios de Vanadio(III)-&Aacute;cido Salic&iacute;lico(H2Sal) con los amino&aacute;cidos Ciste&iacute;na (H2Cys), Histe&iacute;na (HHis), &Aacute;cido Asp&aacute;rtico (H2Asp) y &Aacute;cido Glut&aacute;mico (H2Glu) v&iacute;apotenciom&eacute;trica. Las constantes de formaci&oacute;n reportadas fueron obtenidas a 25 &deg;C empleando en el medio una fuerzai&oacute;nica constante igual a 3,0 mol.L&ndash;1, de manera de mantener los coeficientes de actividad constantes. Todas lascontantes de formaci&oacute;n reportadas fueron obtenidas empleando LETAGROP como Software de c&aacute;lculo, usando elnivel (HL) como referencia; mientras que los diagramas de distribuci&oacute;n de especies fueron obtenidos empleandoHySS como Software de Modelaje. Para el sistema Vanadio(III)-H2Sal-H2Asp se observ&oacute; la formaci&oacute;n de las siguientesespecies: [V(HSal)(H2Asp)]2+, [V(Sal)(H2Asp)]+, V(Sal)(HAsp), [V(Sal)(Asp)]&ndash; y [V(Sal)(Asp)(OH)2]3&ndash;, para el sistemaVanadio(III)-H2Sal-H2Glu se observ&oacute; las especies: [V(Sal)(H2Glu)]+, V(Sal)(HGlu), [V(Sal)(Glu)]- y [V(Sal)(Glu)(OH)]2&ndash;, enel sistema Vanadio(III)-H2Sal-H2Cys, se observ&oacute; la formaci&oacute;n de cuatro complejos: [V(Sal)(H2Cys)]2+, [V(Sal)(HCys)]+,V(Sal)(Cys) y [V(Sal)(Cys)(OH)]_; mientras que para el Sistema Vanadio(III)-H2Sal-HHis, se observ&oacute; los siguientes complejosen soluci&oacute;n: [V(HSal)(HHis)]2+, [V(Sal)(HHis)]+, V(Sal)(His), [V(Sal)(His)(OH)]- y [V(Sal)(His)(OH)2]2&ndash