Aldolases: useful enzymes for the synthesis of anticholesterolemic products

Las aldolasas – enzimas pertenecientes al grupo de las liasas – son biocatalizadores efectivos para realizar reacciones de adición aldólica en medios acuosos, con elevado rendimiento y alta estereoselectividad. Según el sustrato que utilice la enzima, las aldolasas se clasifican en cinco tipos. En particular, 2-desoxy-D-ribosa-5-fosfato aldolasa (DERA) es la única aldolasa capaz de aceptar acetaldehído como sustrato dador nucleofílico. A la vez, se ha comprobado que DERA es capaz de catalizar una doble adición empleando tres moléculas de acetaldehído cuando éste es el único sustrato. Esta particularidad ha hecho que, en los últimos años, DERA sea utilizada en la síntesis de estatinas, drogas empleadas para el control del nivel de colesterol en sangre. Constantemente se invierten esfuerzos para lograr estructuras análogas que reduzcan efectos secundarios adversos y que resulten más potentes médicamente. En nuestro laboratorio se están desarrollando nuevos análogos de estatinas empleando DERA de Pectobacterium atrosepticum.Aldolases, enzymes that belong to the group of lyases, are useful biocatalysts to perform aldol addition reactions in aqueous media, in high yields and stereo selectively. According to the donor substrate, aldolases are classified into five types. In particular, 2-deoxy-D-ribose-5-phosphate aldolase (DERA) is the only aldolase capable of accepting acetaldehyde as donor substrate. In addition, it has been shown that when acetaldehyde is the only availabre substrate, DERA is able to catalyze a double aldol addition using three acetaldehyde molecules.. As a result, in recent years, DERA has been employed for the synthesis of statins, drugs used to control cholesterol level in blood. Efforts are constantly being made to achieve new structures with fewer adverse side effects and improved medicinal efficiency. In our laboratory we are developing new statin analogs using DERA from Pectobacterium atrosepticum.Fil: Fernández Varela, Romina Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Grupo Vinculado al INGEBI- Laboratorio de Biocatálisis y Biotransformaciones - LBB - UNQUI; ArgentinaFil: Iribarren, Adolfo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Grupo Vinculado al INGEBI- Laboratorio de Biocatálisis y Biotransformaciones - LBB - UNQUI; ArgentinaFil: Lewkowicz, Elizabeth Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Grupo Vinculado al INGEBI- Laboratorio de Biocatálisis y Biotransformaciones - LBB - UNQUI; Argentin

Synthetic Activity of Recombinant Whole Cell Biocatalysts Containing 2-Deoxy-D-ribose-5-phosphate Aldolase from Pectobacterium atrosepticum

In nature 2-deoxy-D-ribose-5-phosphate aldolase (DERA) catalyses the reversible formation of 2-deoxyribose 5-phosphate from D-glyceraldehyde 3-phosphate and acetaldehyde. In addition, this enzyme can use acetaldehyde as the sole substrate, resulting in a tandem aldol reaction, yielding 2,4,6-trideoxy-D-erythro-hexapyranose, which spontaneously cyclizes. This reaction is very useful for the synthesis of the side chain of statin-type drugs used to decrease cholesterol levels in blood. One of the main challenges in the use of DERA in industrial processes, where high substrate loads are needed to achieve the desired productivity, is its inactivation by high acetaldehyde concentration. In this work, the utility of different variants of Pectobacterium atrosepticum DERA (PaDERA) as whole cell biocatalysts to synthesize 2-deoxyribose 5-phosphate and 2,4,6-trideoxy-D-erythro-hexapyranose was analysed. Under optimized conditions, E. coli BL21 (PaDERA C-His AA C49M) whole cells yields 99 % of both products. Furthermore, this enzyme is able to tolerate 500 mM acetaldehyde in a whole-cell experiment which makes it suitable for industrial applications.Fil: Fernández Varela, Romina Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Grupo Vinculado al INGEBI- Laboratorio de Biocatálisis y Biotransformaciones - LBB - UNQUI; ArgentinaFil: Valino, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Área Química. Laboratorio de Biotransformaciones; ArgentinaFil: Abdelraheem, Eman. Delft University of Technology; Países BajosFil: Médici, Rosario. Delft University of Technology; Países BajosFil: Martínez Sayé, Melisa Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Hagedoorn, Peter-Leon. Delft University of Technology; Países BajosFil: Hanefeld, Ulf. Delft University of Technology; Países BajosFil: Iribarren, Adolfo Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Grupo Vinculado al INGEBI- Laboratorio de Biocatálisis y Biotransformaciones - LBB - UNQUI; ArgentinaFil: Lewkowicz, Elizabeth Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres". Grupo Vinculado al INGEBI- Laboratorio de Biocatálisis y Biotransformaciones - LBB - UNQUI; Argentin

Methyltransferases: Functions and Applications

In this review the current state of the art of S-adenosylmethionine (SAM)-dependent methyltransferases and SAM are evaluated. Their structural classification and diversity is introduced and key mechanistic aspects presented which are then detailed further. Then, catalytic SAM as a target for drugs and approaches to utilise SAM as a cofactor in synthesis is introduced with different recycling approaches evaluated. The use of SAM analogues are also described. Finally O-, N-, C- and S-MTs, their synthetic applications and potential for compound diversification is given

Spanish Norms for Mini-SEA (Mini Social Cognition and Emotional Assessment) in adults in Buenos Aires

Introducción y objetivos: El Mini-SEA es una evaluación cognitiva rápida para estudiar la cognición social. Consiste en una versión de la Prueba de faux pas y una prueba de reconocimiento emocional. El objetivo deltrabajo fue obtener los primeros valores normativos del Mini-SEA de habla hispana. Material y métodos: Sereclutaron 64 voluntarios sanos que fueron evaluados con el Mini-SEA por neuropsicólogos especializados dedos centros especializados en Buenos Aires. Resultados: La media (M) total fue de 25+/- 4. La M del Score delfaux pas fue de 12,5+/- 2,4 y del Score del Reconocimiento Emocional fue 12,8+/- 1,5. Se dividió la muestraen 4 grupos etarios: Grupo 1 (<50 años), Grupo 2 (50-59 años), Grupo 3 (60-69 años) y Grupo 4 (más de 70años). Se hallaron diferencias en el continuo de la edad en el puntaje del Reconocimiento Emocional entre elgrupo 1 y 4 (p<0,05) y entre el grupo 3 y el 4 (p<0,01), no así en la prueba modificada del faux pas. Conclusión:Este estudio presenta los primeros valores normativos del Mini-SEA para una población de habla hispana. Esuna prueba rápida y fácil y permite estudiar la cognición social de forma adecuada y precisa sobre todo enestadios prodrómicos de enfermedades neurodegenerativas.Introduction and objective: The Mini-SEA is a quick and brief cognitive assessment test developed to study social cognition. It consists of a modified version of the faux pas Test and an emotional recognition test based on Ekman’s faces. The objective of this work was to obtain the first Spanish Speaking norms for the Mini-SEA test. Material and methods: 64 healthy volunteers, between 35 and 80 years old, were recruited and evaluated with the Mini-SEA by specialized neuropsychologists from the Cities of Buenos Aires and La Plata, both in the Province of Buenos Aires, Argentina. Results: The total mean (M) of the Mini-SEA was 25 +/- 4. The M of the faux pas Score was 12.5 +/- 2.4 and the M of the Emotional Recognition Score was 12.8 +/- 1.5. The sample was divided into 4 age groups: Group 1 (<50 years), Group 2 (50-59 years), Group 3 (60-69 years) and Group 4 (more than 70 years). Differences were found in the age continuum in the Emotional Recognition score between group 1 and 4 (p <0.05) and between group 3 and 4 (p <0.01), but not in the Faux Pas Score. Conclusion:This study presents the first normative values of the Mini-SEA Social Cognition test for a Spanish-speaking population. The Mini-SEA, being a quick and easy to administer test, allows the study of social cognition in an adequate and precise way, especially in prodromal stages of neurodegenerative disease.Fil: Clarens, Maria Florencia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Crivelli, Lucía. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Martin, Maria Eugenia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Fernández, Rodrigo Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Canyazo, Carlos. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Arruabarrena, Micaela. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Tabernero, Maria Eugenia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Cervino, Cecilia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Varela, Yanina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Prestupa, Romina Vanesa. Instituto de Neurociencias Alexander Luria; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Pereyra, Lucrecia. Instituto de Neurociencias Alexander Luria; ArgentinaFil: Rossi, Francina. Instituto de Neurociencias Alexander Luria; ArgentinaFil: Sarasola, Ruben. Instituto de Neurociencias Alexander Luria; ArgentinaFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

N-3 PUFA Supplementation Triggers PPAR-α Activation and PPAR-α/NF-κB Interaction: Anti-Inflammatory Implications in Liver Ischemia-Reperfusion Injury

Dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to rats preconditions the liver against ischemia-reperfusion (IR) injury, with reduction of the enhanced nuclear factor-κB (NF-κB) functionality occurring in the early phase of IR injury, and recovery of IR-induced pro-inflammatory cytokine response. The aim of the present study was to test the hypothesis that liver preconditioning by n-3 PUFA is exerted through peroxisone proliferator-activated receptor α (PPAR-α) activation and interference with NF-κB activation. For this purpose we evaluated the formation of PPAR-α/NF-κBp65 complexes in relation to changes in PPAR-α activation, IκB-α phosphorylation and serum levels and expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α in a model of hepatic IR-injury (1 h of ischemia and 20 h of reperfusion) or sham laparotomy (controls) in male Sprague Dawley rats. Animals were previously supplemented for 7 days with encapsulated fish oil (General Nutrition Corp., Pittsburg, PA) or isovolumetric amounts of saline (controls). Normalization of IR-altered parameters of liver injury (serum transaminases and liver morphology) was achieved by dietary n-3 PUFA supplementation. EPA and DHA suppression of the early IR-induced NF-κB activation was paralleled by generation of PPAR-α/NF-κBp65 complexes, in concomitance with normalization of the IR-induced IκB-α phosphorylation. PPAR-α activation by n-3 PUFA was evidenced by enhancement in the expression of the PPAR-α-regulated Acyl-CoA oxidase (Acox) and Carnitine-Palmitoyl-CoA transferase I (CPT-I) genes. Consistent with these findings, normalization of IR-induced expression and serum levels of NF-κB-controlled cytokines IL-lβ and TNF-α was observed at 20 h of reperfusion. Taken together, these findings point to an antagonistic effect of PPAR-α on NF-κB-controlled transcription of pro-inflammatory mediators. This effect is associated with the formation of PPAR-α/NF-κBp65 complexes and enhanced cytosolic IκB-α stability, as major preconditioning mechanisms induced by n-3 PUFA supplementation against IR liver injury

An Energy-Reduced Mediterranean Diet, Physical Activity, and Body Composition

[ENG]Importance Strategies targeting body composition may help prevent chronic diseases in persons with excess weight, but randomized clinical trials evaluating lifestyle interventions have rarely reported effects on directly quantified body composition. OBJECTIVE To evaluate the effects of a lifestyle weight-loss intervention on changes in overall and regional body composition. DESIGN, SETTING, AND PARTICIPANTS The ongoing Prevención con Dieta Mediterránea-Plus (PREDIMED-Plus) randomized clinical trial is designed to test the effect of the intervention on cardiovascular disease prevention after 8 years of follow-up. The trial is being conducted in 23 Spanish research centers and includes men and women (age 55-75 years) with body mass index between 27 and 40 and metabolic syndrome. The trial reported herein is an interim subgroup analysis of the intermediate outcome body composition after 3-year follow-up, and data analysis was conducted from February 1 to November 30, 2022. Of 6874 total PREDIMED-Plus participants, a subsample of 1521 individuals, coming from centers with access to a dual energy x-ray absorptiometry device, underwent body composition measurements at 3 time points. INTERVENTION Participants were randomly allocated to a multifactorial intervention based on an energy-reduced Mediterranean diet (MedDiet) and increased physical activity (PA) or to a control group based on usual care, with advice to follow an ad libitum MedDiet, but no physical activity promotion. MAIN OUTCOMES AND MEASURES The outcomes (continuous) were 3-year changes in total fat and lean mass (expressed as percentages of body mass) and visceral fat (in grams), tested using multivariable linear mixed-effects models. Clinical relevance of changes in body components (dichotomous) was assessed based on 5% or more improvements in baseline values, using logistic regression. Main analyses were performed in the evaluable population (completers only) and in sensitivity analyses, multiple imputation was performed to include data of participants lost to follow-up (intention-to-treat analyses). RESULTS A total of 1521 individuals were included (mean [SD] age, 65.3 [5.0] years; 52.1% men). In comparison with the control group (n=761), participants in the intervention arm (n=760) showed greater reductions in the percentage of total fat (between group differences after 1-year, −0.94% [95% CI, −1.19 to −0.69]; 3 years, −0.38% [95% CI, −0.64 to −0.12] and visceral fat storage after 1 year, -126 g [95% CI, −179 to −73.3 g]; 3 years, −70.4 g [95% CI, −126 to −15.2 g] and greater increases in the percentage of total lean mass at 1 year, 0.88% [95% CI, 0.63%-1.12%]; 3-years 0.34% [95%CI, 0.09%-0.60%]). The intervention group was more likely to show improvements of 5% or more in baseline body components (absolute risk reduction after 1 year, 13% for total fat mass, 11% for total lean mass, and 14% for visceral fat mass; after 3-years: 6% for total fat mass, 6% for total lean mass, and 8% for visceral fat mass). The number of participants needed to treat was between 12 and 17 to attain at least 1 individual with possibly clinically meaningful improvements in body composition. CONCLUSIONS AND RELEVANCE The findings of this trial suggest a weight-loss lifestyle intervention based on an energy-reduced MedDiet and physical activity significantly reduced total and visceral fat and attenuated age-related losses of lean mass in older adults with overweight or obesity and metabolic syndrome. Continued follow-up is warranted to confirm the long-term consequences of these changes on cardiovascular clinical end points.S

Development and validation of a clinical score to estimate progression to severe or critical state in Covid-19 pneumonia hospitalized patients

The prognosis of a patient with Covid-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. A retrospective study was performed of patients admitted with Covid-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, analytical, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. During the study period 1,152 patients presented with Covid-19 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 hours of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤5%, 6-25%, and >25% exhibited disease progression, respectively. A simple risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis.Carlos III Health Institute, Spain, Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER)Instituto de Salud Carlos II

Proyecto, investigación e innovación en urbanismo, arquitectura y diseño industrial

Actas de congresoLas VII Jornadas de Investigación “Encuentro y Reflexión” y I Jornadas de Investigación de becarios y doctorandos. Proyecto, investigación e innovación en Urbanismo, Arquitectura y Diseño Industrial se centraron en cuatro ejes: el proyecto; la dimensión tecnológica y la gestión; la dimensión social y cultural y la enseñanza en Arquitectura, Urbanismo y Diseño Industrial, sustentados en las líneas prioritarias de investigación definidas epistemológicamente en el Consejo Asesor de Ciencia y Tecnología de esta Universidad Nacional de Córdoba. Con el objetivo de afianzar continuidad, formación y transferencia de métodos, metodología y recursos se incorporó becarios y doctorandos de los Institutos de investigación. La Comisión Honoraria la integraron las tres Secretarias de Investigación de la Facultad, arquitectas Marta Polo, quien fundó y María del Carmen Franchello y Nora Gutiérrez Crespo quienes continuaron la tradición de la buena práctica del debate en la cotidianeidad de la propia Facultad. Los textos que conforman las VII Jornadas son los avances y resultados de las investigaciones realizadas en el bienio 2016-2018.Fil: Novello, María Alejandra. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Repiso, Luciana. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Mir, Guillermo. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Brizuela, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Herrera, Fernanda. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Períes, Lucas. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Romo, Claudia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Gordillo, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Andrade, Elena Beatriz. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; Argentin

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake