Beneficial effect of ursodeoxycholic acid in patients with acyl-CoA oxidase 2 (ACOX2) deficiency-associated hypertransaminasemia

Background and aims: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3?,7?,12?-trihydroxy-5?-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration. Methods and results: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by high-performance liquid chromatography-mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH-7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1-S/XBP1-U ratio), and BAX? expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt-based cell viability test). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH. Conclusions: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.Funding information: This study was supported by the following grants: CIBERehd (EHD15PI05/2016); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI19/00819 and PI20/00189), co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”; “Junta de Castilla y León” (SA074P20); Fundació Marato TV3 (201916–31); AECC Scientific Foundation (2017/2020), Spain; and “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from grants PID2019-111669RBI-100, PID2020-115055RB-I00 from Plan Nacional de I+D funded by the “Agencia Estatal de Investigación” (AEI) and the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA/NIH, as well as support from AGAUR of the “Generalitat de Catalunya” SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network. Marta Alonso-Peña was the recipient of a predoctoral fellowship from “Ministerio de Educación, Cultura y Deporte” (BOE-A-2015-9456; FPU-14/00214) and a Mobility Grant for Short Stays from “Ministerio de Ciencia, Innovación y Universidades” (EST17/00186). Ricardo Espinosa-Escudero is the recipient of a predoctoral fellowship from “Junta de Castilla y León” and “Fondo Social Europeo” (EDU/574/2018). The funding sources were not involved in the research design or preparation of the article

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

4to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

Este volumen acoge la memoria académica de la Cuarta edición del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2017, desarrollado entre el 29 de noviembre y el 1 de diciembre de 2017 y organizado por la Universidad Politécnica Salesiana (UPS) en su sede de Guayaquil. El Congreso ofreció un espacio para la presentación, difusión e intercambio de importantes investigaciones nacionales e internacionales ante la comunidad universitaria que se dio cita en el encuentro. El uso de herramientas tecnológicas para la gestión de los trabajos de investigación como la plataforma Open Conference Systems y la web de presentación del Congreso http://citis.blog.ups.edu.ec/, hicieron de CITIS 2017 un verdadero referente entre los congresos que se desarrollaron en el país. La preocupación de nuestra Universidad, de presentar espacios que ayuden a generar nuevos y mejores cambios en la dimensión humana y social de nuestro entorno, hace que se persiga en cada edición del evento la presentación de trabajos con calidad creciente en cuanto a su producción científica. Quienes estuvimos al frente de la organización, dejamos plasmado en estas memorias académicas el intenso y prolífico trabajo de los días de realización del Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad al alcance de todos y todas

Boletín Clínico, Vol. 05, No. 04. Febrero

Ley 235 de 1938 * Biblioteca de la facultad. Obra recibidas * Palabras del Dr. Emilio Robledo. Pag.141–144 * Comentario a un caso de leucemia mieloide crónica. Pag.145–155 * Contagio de la lepra. Pag.156–162 * Las reacciones serológicas en la lepra. Pag.163–165 * Consideraciones alrededor de un foco leprogeno. Pag.166–168 * Informe sobre lazaretos. Pag.169–181 * Notas sobre apendicitis aguda. Pag.182–191 * Biblioteca de la faculta

Classical Least Squares-Assisted Mid-Infrared (MIR) Laser Spectroscopy Detection of High Explosives on Fabrics

Mid-infrared (MIR) laser spectroscopy was used to detect the presence of residues of high explosives (HEs) on fabrics. The discrimination of the vibrational signals of HEs from a highly MIR-absorbing substrate was achieved by a simple and fast spectral evaluation without preparation of standards using the classical least squares (CLS) algorithm. Classical least squares focuses on minimizing the differences between the spectral features of the actual spectra acquired using MIR spectroscopy and the spectral features of calculated spectra modeled from linear combinations of the spectra of neat components: HEs, fabrics, and bias. Samples in several combinations of cotton fabrics/HEs were used to validate the methodology. Several experiments were performed focusing on binary, ternary, and quaternary mixtures of TNT, RDX, PETN, and fabrics. The parameters obtained from linear combinations of the calculated spectra were used to perform discrimination analyses and to determine the sensitivity and selectivity of HEs with respect to the substrates and to each other. However, discrimination analysis was not necessary to achieve successful detection of HEs on cotton fabric substrates. The RDX signals (mRDX>0.02 mg) on cotton were used to calculate the limit of detection (LOD). The signalto- noise ratios (S/N) calculated from the spectra of cotton dosed with decreasing masses of RDX until S/N&3 resulted in a LOD of 15–33 mg, depending on the vibrational band used. Linear fits generated by comparing the mass dosed RDX with the fraction predicted were also used to calculate the LOD based on the uncertainty of the blank and the slope. This procedure resulted in a LOD of 58 mg. Probably the most representative value of the method LOD was calculated using an interpolation of a threshold determined using the predicted average value for the blank plus 3.28 times the standard deviations (p-value threshold) for low surface dosages of RDX (LOD¼40 mg). The contribution demonstrates that to achieve HE detection on fabrics using the proposed algorithm, i.e., determining the presence/absence of HEs on the substrates, the library must contain the spectra of HEs, substrates, and potential interferents or that these spectra be added to the models in the field. If the model does not contain the spectra of the fabric components, there is a high probability of finding false positives for clean samples (no HEs) and a low probability for failed detection in samples with HEs. More work will be required to demonstrate that these new approaches to HE detection work on real-world samples and when contaminating materials are present in the samples

HIV-Related High Risk Sexual Behaviors and Practices Among Women in Bogotá, Colombia

Determinants associated with high-risk sexual behaviors were investigated in 1,133 sexually active women in Bogotá, Colombia. A self-administered questionnaire was completed by two groups of women: 721 representing the general population (GP), and 412 commercial sex workers (CSWs). High-risk sexual behaviors for HIV/AIDS were evident in both groups. Nevertheless, consistent condom use was reported by only 6% of the GP group, as compared to 67% of the CSWs. Failure to recognize high-risk routes for HIV infection was indicated in 69% of the GP women for anal sex, and by the majority of both groups for intercourse during menses (56% GP women and 54% CSWs). Multivariate analysis revealed that education level, actual age, and age of first sex experience were significant predictors of high-risk sexual practices. The necessity for educational programs regarding high-risk sexual practices and risk of HIV/ AIDS is evident for HIV/AIDS prevention

Boletín Clínico, Vol. 03, No. 01. Septiembre

Conferencia dictada en la clase de histologia por le profesor titular Williamson Uribe, Juan p.3-11 Lucha anticancerosa Orozco V., Alfonso p.12-14 Piomiositis Restrepo, Jose Miguel p.15-17 Dientes embrionario de probable origen sifilico Restrepo, Jose Miguel p.17-19 Datos relativos a mortalidad en 1889, en antioquia (colombia) publicados en 1904 con estas notas Londoño, Juan Bautista p.20-34 Algunas curiosas anomalias anatomicas Osorio Isaza, Antonio p.35-38 Hemorragia en el tracto gastrointestinal coincidiendo con la amigdalectomia Bernal Moreno, Jaime p.39-41 La lepra en Colombia Grau, Luis Carlos p.42-48 Becas para mujeres Boletin Clinico anex

Abstract WMP85: Target Stroke Implementation: Best Practice Strategies Cut Thrombolysis Time to <30 minutes in a 1,550 Bed Academic Urban County Hospital

Introduction: Thrombolytic window for acute ischemic stroke is brief and crucial. The AHA/ASA Target: Stroke Best Practice Strategies (TSBPS) aim to help hospitals improve thrombolysis door-to-needle (DTN) time. We assessed long-term efficacy of TSBPS to reduce DTN in a tertiary care hospital. Methods: We initiated a quality improvement program across one regional academic medical center (1,550 beds, 900 annual stroke admissions) that serves a multi-ethnic population by establishing a multidisciplinary DTN committee to assess causes of delayed DTN and implement focused TSBPS. Strategies included stroke team pre-admission notification, direct transfer to CT scanner, storing and administering IV rt-PA at CT scanner, and immediate stakeholder feedback. Door-to-CT, DTN, CT to IV rt-PA and door-to-groin (DTG) times were analyzed prospectively in consecutive IV rt-PA treated patients over 27 months pre-implementation and 13 months post-implementation. Results: A total of 148 patients were included in the pre-implementation and 126 patients in the post-implementation group. The two groups had similar demographics, comorbidities, anticoagulation status, pre-thrombolysis hypertension treatment, stroke severity (median NIHSS 11 (6-18) vs. 11 (5-17), p= 0.483), arrival by EMS (96% vs. 97%, p=0.708), and arrival after hours. Post implementation, reductions in treatment times were observed for median DTN (IQR) 59 (52-80) to 28.5 (20-41) min (p<0.001), door-to-CT time 17 (14-21) to 16 (12-19) min (p=0.016), CT-to-IV rt-PA time 43 (31-59) to 13 (6-23) min (p<0.001), and DTG time 164 (136-188) min (n=37) to 86 (63-103) min (n=51) (p<0.001). Overall monthly IV r-tPA administration increased post-implementation (5.5 vs. 9.8, p<0.001). Rate of symptomatic intracranial hemorrhage (2.7% vs. 3.2%, p=0.817) and treatment of stroke mimics (9% vs. 13%, p=0.311) were similar pre- and post-implementation. Conclusions: In this study, delay in IV rt-PA administration was predominantly related to prolonged CT to IVrt-PA time. DTN committee implementation is a simple, low-cost intervention, that significantly reduced DTN and DTG with persistent effect and no increase in symptomatic intracranial hemorrhage or stroke mimic treatment rate