A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients / Una consideración terapéutica diferencial para el uso de corticoesteroides en COVID-19 según los diferentes fenotipos clínicos establecidos en pacientes críticos

bjective To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design A secondary analysis derived from multicenter, observational study. Setting Critical Care Units. Patients Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions Corticosteroids vs. no corticosteroids. Main variables of interest Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98–1.15). Corticosteroids were administered in 298/537 (55.5%) patients of “A” phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55–1.33]). A total of 338/623 (54.2%) patients in “B” phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49–1.05]). Finally, 535/857 (62.4%) patients in “C” phenotype received corticosteroids. In this phenotype HR (0.75 [0.58–0.98]) and sHR (0.79 [0.63–0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment (AU)

Objetivo Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño Análisis secundario de estudio multicéntrico observacional. Ámbito UCI. Pacientes Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención Corticoides vs. no corticoides. Variables de interés principales A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR=0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR=0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC (AU)

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Características clínicas y epidemiológicas asociadas con internación en niños con COVID-19 en un hospital pediátrico de alta complejidad: Estudio de cohorte enero-marzo 2022 / Clinical and epidemiologic characteristics associated with hospital admission in children with COVID19 in a tertiary-care pediatric hospital: A January-March 2022 cohort study

Introducción: La proporción de casos reportados de niños y adolescentes con COVID-19 aumenta progresivamente. La hospitalización relacionada con COVID-19 en niños es infrecuente, pero causa morbilidad y sobrecarga al sistema de salud. Objetivos: Describir las características clínicas y evolutivas de los niños con diagnóstico de COVID-19 en un hospital pediátrico de alta complejidad. Comparar los pacientes que requirieron internación y los que no. Material y métodos: Cohorte prospectiva. Se incluyeron todos los pacientes con diagnóstico virológico de COVID-19 desde 1.1.2022 a 1.3.22 en un hospital pediátrico de alta complejidad. Se compararon los antecedentes, características clínicas y evolutivas de los pacientes según requirieran o no internación. Se utilizó STATA 16. Resultados: n: 1764 pacientes, de ellos 958 eran varones (54%). La mediana de edad fue 56 meses (RIC 17-116). Tenían enfermedad de base 789 pacientes (46%). Las más frecuentes fueron: enfermedad oncohematológica 215 (12%), neurológica 103 pacientes (6%) , enfermedad pulmonar crónica 68 (4%), cardiopatías congénitas 65 (4%) y síndrome genético 57 pacientes (3%). Eran inmunosuprimidos: 292 (17%). Presentaron síntomas relacionados con COVID-19 1319 pacientes (79%). Requirieron internación 591 (34%). Tuvieron coinfección con otros virus respiratorios 33 pacientes (2%). Ingresaron a Cuidados intensivos en relación a la COVID-19 22 pacientes (1.3%) y fallecieron en relación con la infección 8 (0.5%). En el análisis univariado, la presencia de comorbilidades, la coinfección viral y la inmunosupresión se asociaron estadísticamente con el requerimiento de internación. El antecedente de 2 o más dosis de vacuna para SARS-CoV-2 fue un factor protector para la internación en los mayores de 3 años. En el modelo multivariado, los pacientes menores de 3 años (OR 6.5, IC95% 1.2-36.8, p 0.03), con comorbilidades (OR 2.04, IC 95% 1.7- 3.3, p 0.00) y los huéspedes inmunocomprometidos (OR 2.89, IC95% 2.1-4.1, p 0.00) tuvieron más riesgo de internación. Ajustado por el resto de las variables, haber recibido dos o más dosis de vacuna fue un factor protector para la internación (OR 0.65, IC 95% 0.49-0.87, p<0.01). Conclusiones: En este estudio de cohorte prospectivo de niños con diagnóstico confirmado de COVID-19 predominó la enfermedad sintomática. Fueron admitidos en relación con el COVID-19, 34% de los pacientes. La vacunación con dos o más dosis fue un factor protector para la internación en el modelo multivariado. Además, se asociaron estadísticamente con la hospitalización, la edad menor de 3 años, las comorbilidades previas y la inmunosupresión (AU)

Introduction: The rate of reported cases of children and adolescents with COVID-19 is progressively increasing. COVID-19-related hospital admission in children is uncommon, but leads to morbidity and places a burden on the healthcare system. Objectives: To describe the clinical characteristics and outcome of children diagnosed with COVID-19 in a pediatric tertiary-care hospital and to compare patients who required hospital admission with those who did not. Material and methods: A prospective cohort study. All patients with a virological diagnosis of COVID-19 seen between 1.1.2022 and 1.3.22 in a tertiary-care pediatric hospital were included. We compared patient history, clinical characteristics, and outcome according to whether or not they required hospital admission. STATA 16 was used. Results: n: 1764 patients, 958 of whom were male (54%). The median age was 56 months (IQR, 17- 116). Overall, 789 patients had an underlying disease (46%), the most frequent of which were hematology-oncology disease in 215 patients (12%), neurological disease in 103 (6%), chronic lung disease in 68 (4%), congenital heart disease in 65 (4%), and a genetic syndrome in 57 (3%); 292 were immunosuppressed (17%). Overall, 1319 patients (79%) had COVID-19-related symptoms and 591 (34%) required hospital admission. A coinfection with other respiratory viruses was observed in 33 patients (2%). Intensive care admission due to COVID-19 was required in 22 patients (1.3%) and 8 (0.5%) died with COVID-19. In univariate analysis, the presence of comorbidities, viral coinfecton, and immunosuppression were statistically significantly associated with the need for hospitalization. A history of two or more doses of the SARSCoV2 vaccine was a protective factor against hospital admission in children older than 3 years. In the multivariate model, patients younger than 3 years (OR 6.5, 95% CI 1.2-36.8, p 0.03), with comorbidities (OR 2.04, 95%CI 1.7-3.3, p 0.00) and immunocompromised hosts (OR 2.89, 95% CI 2.1-4.1, p 0.00) had a higher risk of hospital admission. When adjusting for the remaining variables, having received two or more doses of the vaccine was found to be a protective factor against hospital admission (OR 0.65, 95% CI 0.49-0.87, p<0.01). Conclusions: In this prospective cohort study of children with a confirmed diagnosis of COVID-19, symptomatic disease predominated. Thirty-four percent of the patients were admitted for COVID-19. Vaccination with two or more doses was a protective factor against hospitalization in the multivariate model. In addition, age younger than 3 years, previous comorbidities, and immunosuppression were statistically associated with hospital admission (AU)

A follow-up on quantitative and qualitative olfactory dysfunction and other symptoms in patients recovering from COVID-19 smell loss.

BACKGROUND: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. METHODS: This longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete a follow-up survey (S2). Between September 2020 and February 2021, 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. RESULTS: At follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. CONCLUSIONS: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long-term sequelae; more research into treatment options is strongly warranted given that even conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health.

Cobalamin cbiP mutant shows decreased tolerance to low temperature and copper stress in Listeria monocytogenes.

BACKGROUND: Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans. This pathogen activates multiple regulatory mechanisms in response to stress, and cobalamin biosynthesis might have a potential role in bacterial protection. Low temperature is a strategy used in the food industry to control bacteria proliferation; however, L. monocytogenes can grow in cold temperatures and overcome different stress conditions. In this study we selected L. monocytogenes List2-2, a strain with high tolerance to the combination of low temperature + copper, to understand whether the cobalamin biosynthesis pathway is part of the tolerance mechanism to this stress condition. For this, we characterized the transcription level of three cobalamin biosynthesis-related genes (cbiP, cbiB, and cysG) and the eutV gene, a transcriptional regulator encoding gene involved in ethanolamine metabolism, in L. monocytogenes strain List2-2 growing simultaneously under two environmental stressors: low temperature (8 °C) + copper (0.5 mM of CuSO4 × 5H2O). In addition, the gene cbiP, which encodes an essential cobyric acid synthase required in the cobalamin pathway, was deleted by homologous recombination to evaluate the impact of this gene in L. monocytogenes tolerance to a low temperature (8 °C) + different copper concentrations. RESULTS: By analyzing the KEGG pathway database, twenty-two genes were involved in the cobalamin biosynthesis pathway in L. monocytogenes List2-2. The expression of genes cbiP, cbiB, and cysG, and eutV increased 6 h after the exposure to low temperature + copper. The cobalamin cbiP mutant strain List2-2ΔcbiP showed less tolerance to low temperature + copper (3 mM) than the wild-type L. monocytogenes List2-2. The addition of cyanocobalamin (5 nM) to the medium reverted the phenotype observed in List2-2ΔcbiP. CONCLUSION: These results indicate that cobalamin biosynthesis is necessary for L. monocytogenes growth under stress and that the cbiP gene may play a role in the survival and growth of L. monocytogenes List2-2 at low temperature + copper.

Adaptación transcultural de la versión colombiana de la Escala de Soledad de UCLA en pacientes con diagnóstico de cáncer / Transcultural adaptation of the Colombian version of the UCLA Loneliness Scale in patients diagnosed with cancer

Resumen Introducción: La soledad no deseada es un constructo que se ha relacionado con desenlaces negativos en diferentes aspectos de la salud, incluidos aquellos de los pacientes con cáncer. La escala de soledad de UCLA es un instrumento ampliamente utilizado en el contexto de investigación en salud para medir dicho constructo, y en Colombia la versión 03 de dicho instrumento no se encuentra traducida, ni adaptada transculturalmente. Objetivo: Traducir y adaptar transculturalmente la escala de soledad de UCLA, versión 03 para su uso en pacientes con cáncer en Colombia. Métodos: El proceso de traducción y adaptación transcultural siguió la metodología propuesta por el grupo EORTC, con el objetivo de lograr la equivalencia semántica con la versión original de la escala disponible en inglés. Se realizó una prueba piloto con 20 pacientes colombianos diagnosticados con diferentes tipos de cáncer, que asistieron al Instituto Nacional de Cancerología de Colombia. Resultados: No hubo cambios ni en la traducción de instrucciones ni en las opciones de respuesta. En la versión conciliada se modificó el ítem UC1. En la prueba piloto, dos de 20 pacientes informaron que los ítems UC6, UC7, UC11 y UC19 deberían ser modificados y un paciente mencionó que el ítem UC8 era difícil de entender; sin embargo, no se hicieron cambios dado el bajo número de pacientes que reportaron estos hallazgos, y las sugerencias planteadas podían cambiar el sentido y la equivalencia de los ítems de la escala original. Ninguno de los ítems fue ofensivo para los pacientes. Conclusión: Se generó una versión traducida y adaptada transculturalmente para ser validada en pacientes con cáncer en Colombia.

Abstract Introduction: Unwanted loneliness is a construct that has shown relationships with different negative outcomes of health, including those of patients with cancer. In the context of health research, the UCLA loneliness scale is a widely used instrument for measuring this construct. In Colombia, the 03 version of this instrument has still not been neither translated, nor transculturally adapted. Objective: To translate and perform transcultural adaptation of the UCLA loneliness scale, version 03 for its use in patients having cancer in Colombia. Methods: The process of translation and transcultural adaptation followed the methodology proposed by the EORTC group, aimed at achieving semantic equivalence with the original version of the scale. A pilot test has been made with 20 Colombian patients diagnosed with different types of cancer, attending the Instituto Nacional de Cancerología, Colombia. Results: In the reconciliated version, item UC1 has been modified. There has been not changes neither in translation of instructions, nor in response options. In pilot testing two out of 20 patients reported that items UC6, UC7, UC11 y UC19 should be modified and one patient mentioned that item UC8 was difficult to understand; however, no changes were made taking into account the low number of patients describing similar findings, and because these suggestions could change the semantic equivalence of these items. No items were deemed offensive. Conclusion: It is available a transculturally adapted version of the UCLA loneliness scale, version 03 for its validation in patients with cancer in Colombia.

Gender Differences in Perceived Family Involvement and Perceived Family Control during Emerging Adulthood: A Cross-Country Comparison in Southern Europe.

The aim of the present study was to explore gender differences in perceived parental involvement and perceived psychological and behavioral control during emerging adulthood in two Southern European countries (Spain and Portugal). Data were collected from 491 Portuguese and 552 Spanish undergraduate emerging adults (53.7 % women and 46.3 % men) aged between 18 and 29 years (M = 20.24 and SD = 2.12). Results indicated that women perceived higher levels of parental involvement than men in both countries, and men perceived more behavioral control than women in Portugal. Furthermore, gender was found to moderate the association between perceived parental involvement and perceived psychological and behavioral control differently in each country. Taken together, our findings suggest that gender-differentiated socialization patterns persist during emerging adulthood and that these patterns may be affected by the sociocultural context.

Dynamic of CO2, CH4 and N2O in the Guadalquivir estuary.

The concentration of dissolved CH4 and N2O, as well as the partial pressure of CO2 (pCO2) were studied in the Guadalquivir estuary. Samples were taken in March and April 2018 and 2019, under different rainy and tidal conditions. The available database for summer 2017 (Sierra et al., 2020) was included in the interpretation of the factors that determine the variability of these gases in the Guadalquivir estuary. Two different types of samplings were carried out: a longitudinal transect across the river with salinity values close to zero and another one during two consecutive tidal cycles in the mouth of the estuary. The highest concentrations were found in the upper zone of the estuary and during the low tide. This distribution was related to 4 factors: temperature, salinity, exchange with the atmosphere, and biochemical processes together with the river inputs. Temperature is one of the factors that clearly seems to determine the distribution of gases and fluxes, showing the highest values in the upper zone during the summer of 2017. Intense rains cause a dilution effect of the gas in the water column, this provoked, during the season of spring 2018, an increase in the salinity factor in the distribution of gases in the middle zone. High concentrations of the gases have been linked to production processes in the water column, as well as to benthic production and lateral inputs. While the gases concentrations at the mouth presented values close to those of the equilibrium with the atmosphere, the fluxes in the upper zone of the estuary reached average values of 89.6 mmol m-2 d-1, 121.7 µmol m-2 d-1 and 59.9 µmol m-2 d-1 for CO2, CH4 and N2O, respectively. Generally, water-atmosphere fluxes are positive through the whole study, which means that the estuary acts as a source of these gasses to the atmosphere.

Cobalamin cbiP mutant shows decreased tolerance to low temperature and copper stress in Listeria monocytogenes

BACKGROUND: Listeria monocytogenes is a foodborne pathogen that causes listeriosis in humans. This pathogen activates multiple regulatory mechanisms in response to stress, and cobalamin biosynthesis might have a potential role in bacterial protection. Low temperature is a strategy used in the food industry to control bacteria proliferation; however, L. monocytogenes can grow in cold temperatures and overcome different stress conditions. In this study we selected L. monocytogenes List2-2, a strain with high tolerance to the combination of low temperature +copper, to understand whether the cobalamin biosynthesis pathway is part of the tolerance mechanism to this stress condition. For this, we characterized the transcription level of three cobalamin biosynthesis related genes ( cbiP , cbiB, and cysG ) and the eutV gene, a transcriptional regulator encoding gene involved in ethanolamine metabolism, in L. monocytogenes strain List2-2 growing simultaneously under two environmental stressors: low temperature (8 °C) +copper (0.5 mM of CuSO4 ×5H2O). In addition, the gene cbiP , which encodes an essential cobyric acid synthase required in the cobalamin pathway, was deleted by homologous recombination to evaluate the impact of this gene in L. monocytogenes tolerance to a low temperature (8 °C) +different copper concentrations. RESULTS: By analyzing the KEGG pathway database, twenty-two genes were involved in the cobalamin biosynthesis pathway in L. monocytogenes List2-2. The expression of genes cbiP , cbiB, and cysG, and eutV increased 6 h after the exposure to low temperature +copper. The cobalamin cbiP mutant strain List2-2Δ cbiP showed less tolerance to low temperature +copper (3 mM) than the wild type L. monocytogenes List2-2. The addition of cyanocobalamin (5 nM) to the medium reverted the phenotype observed in List2-2Δ cbiP . CONCLUSION: These results indicate that cobalamin biosynthesis is necessary for L. monocytogenes growth under stress and that the cbiP gene may play a role in the survival and growth of L. monocytogenes List2-2 at low temperature +copper.

Eventos adversos supuestamente atribuibles a la vacunación e inmunización asociados a la vacuna anti-COVID-19 Sputnik V en el personbal del hospital Juan P. Garrahan / Adverse events allegedly attributable to vaccination and immunization with the anti-COVID-19 Sputnik V vaccine in the staff of the Hospital Juan P. Garrahan

Introducción: Debido a la emergencia provocada por la pandemia por el virus SARS-CoV-2 se ha producido una crisis sanitaria global. Una vez disponibles las vacunas, se espera que jueguen un rol decisivo para el control de la enfermedad. Dichas vacunas fueron desarrolladas en tiempo récord por lo que es esencial monitorear su seguridad. Durante la Campaña de Vacunación contra COVID-19, todos los Eventos supuestamente atribuibles a vacunación e inmunización (ESAVI) debieron ser notificados al Ministerio de Salud de la Nación a través del Sistema Integrado de Información Sanitaria de Argentina (SIISA). Materiales y métodos: Se realizó un estudio observacional prospectivo desde el 04/01/2021 al 05/05/2021 en el personal del Hospital Garrahan. Se utilizaron dos métodos de vigilancia de ESAVI. La vigilancia pasiva incluyó las notificaciones voluntarias recibidas de forma telefónica y a través de un cuestionario publicado en intranet. La vigilancia activa se realizó sobre los primeros 947 trabajadores inmunizados, enviando el mismo cuestionario por WhatsApp. Resultados: Hasta el día 05/05/2021 fueron inmunizados 5056 agentes, 4865 con las dos dosis. Se notificaron 473 ESAVI. De ellos, 304 correspondían a la primera dosis y 169 a la segunda. La cantidad de notificaciones según su origen fue de 136 para la vigilancia pasiva, y 333 para la vigilancia activa. Se registraron 5 ESAVI graves; tres anafilaxias, un escotoma secundario a la hipertermia generada por la vacuna y una reacción alérgica grave. Los síntomas locales más frecuentes fueron: dolor, enrojecimiento, hinchazón e induración. Los síntomas sistémicos más frecuentes fueron: fiebre, febrícula, astenia, cefalea, mialgia, artralgia y síntomas gastrointestinales. Como tratamiento en la mayoría de los casos se utilizó paracetamol. Discusión: El presente trabajo logró recolectar un número significativo de notificaciones, brindando información útil al tratarse de una vacuna recientemente aprobada en nuestro país y el mundo. (AU)

Introduction: Due to the SARS-CoV-2 pandemic emergency, a global health crisis has occurred. Once vaccines become available, they are expected to play a decisive role in controlling the disease. These vaccines were developed in record time, and therefore it is essential to monitor their safety. During the COVID-19 Vaccination Campaign, all Events Suspected to be Attributable to Vaccination and Immunization (ESAVI) had to be notified to the National Ministry of Health through the Integrated Health Information System of Argentina (SIISA). Material and methods: A prospective observational study was conducted from 04/01/2021 to 05/05/2021 in the staff of Garrahan Hospital. Two methods of ESAVI surveillance were used. Passive surveillance included voluntary notifications received by telephone and through a questionnaire posted on intranet. Active surveillance was conducted on the first 947 immunized workers, sending the same questionnaire by WhatsApp. Results: Up to 05/05/2021, 5056 workers were immunized, of whom 4865 with two doses. A total of 473 ESAVI were reported. Of these, 304 corresponded to the first dose and 169 to the second. The number of notifications was 136 for passive surveillance and 333 for active surveillance. Five severe ESAVIs were recorded; three anaphylaxis, one scotoma secondary to vaccine-generated hyperthermia, and one severe allergic reaction. The most frequent local symptoms were: pain, redness, swelling, and induration. The most frequent systemic symptoms were: mild fever or fever, asthenia, headache, myalgia, arthralgia, and gastrointestinal symptoms. Paracetamol was used as treatment in most cases. Discussion: In the present study a significant number of notifications was collected, providing useful information on a vaccine recently approved in our country and in the world (AU)

Second GHEP-ISFG exercise for DVI: "DNA-led" victims' identification in a simulated air crash.

The Spanish and Portuguese-Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) has organized a second collaborative exercise on a simulated case of Disaster Victim Identification (DVI), with the participation of eighteen laboratories. The exercise focused on the analysis of a simulated plane crash case of medium-size resulting in 66 victims with varying degrees of fragmentation of the bodies (with commingled remains). As an additional difficulty, this second exercise included 21 related victims belonging to 6 families among the 66 missings to be identified. A total number of 228 post-mortem samples were represented with aSTR and mtDNA profiles, with a proportion of partial aSTR profiles simulating charred remains. To perform the exercise, participants were provided with aSTR and mtDNA data of 51 reference pedigrees -some of which deficient-including 128 donors for identification purposes. The exercise consisted firstly in the comparison of the post-mortem genetic profiles in order to re-associate fragmented remains to the same individual and secondly in the identification of the re-associated remains by comparing aSTR and mtDNA profiles with reference pedigrees using pre-established thresholds to report a positive identification. Regarding the results of the post-mortem samples re-associations, only a small number of discrepancies among participants were detected, all of which were from just a few labs. However, in the identification process by kinship analysis with family references, there were more discrepancies in comparison to the correct results. The identification results of single victims yielded fewer problems than the identification of multiple related victims within the same family groups. Several reasons for the discrepant results were detected: a) the identity/non-identity hypotheses were sometimes wrongly expressed in the likelihood ratio calculations, b) some laboratories failed to use all family references to report the DNA match, c) In families with several related victims, some laboratories firstly identified some victims and then unnecessarily used their genetic information to identify the remaining victims within the family, d) some laboratories did not correctly use "prior odds" values for the Bayesian treatment of the episode for both post-mortem/post-mortem re-associations as well as the ante-mortem/post-mortem comparisons to evaluate the probability of identity. For some of the above reasons, certain laboratories failed to identify some victims. This simulated "DNA-led" identification exercise may help forensic genetic laboratories to gain experience and expertize for DVI or MPI in using genetic data and comparing their own results with the ones in this collaborative exercise.

"Greenhouse gas dynamics in a coastal lagoon during the recovery of the macrophyte meadow (Mar Menor, SE Spain)".

The Mar Menor is a hypersaline coastal lagoon with salinity values ranging from 41.9 to 45.5. The system is subjected to a high anthropic pressure that causes an intense eutrophication process, followed by a recovery of the macrophyte meadows. This study focuses on the distribution of the main greenhouse gases (CO2, CH4 and N2O) and was carried out in the extreme seasonal conditions of winter and summer during the year 2018. Sediment-water-atmosphere exchanges and biochemical processes in the water column appeared to be the main factors to explain the variability of these gases. Dissolved Inorganic Carbon (DIC), CH4 and N2O benthic fluxes values obtained in this study, were of 91 ± 29 mmol m-2 d-1, 3.9 ± 1.9 µmol m-2 d-1 and -0.65 µmol m-2 d-1, respectively, along with an important seasonal variation observed, with an increase of DIC and CH4 benthic fluxes during the summer season. Mean values of partial pressure of CO2 (pCO2) in surface water were of 579 µatm in winter and 464 µatm in summer, therefore we can establish that the Mar Menor acts as a source of this gas emitting 3.3 ± 3.0 mmol CO2 m-2 d-1 to the atmosphere. In spite of this, the Mar Menor has a strong autotrophic behaviour partly due to the recovery of the macrophyte meadows, presenting an estimated NEP of 101 mmol m-2 d-1. Regarding to CH4, the mean fluxes to the atmosphere were of 8.0 ± 5.8 µmol m-2 d-1 and there was evidence of CH4 production in the water column that increased in summer. Last of all, in the case of N2O the system acts as a sink with values of -0.65 ± 0.5 µmol m-2 d-1, presenting an intake of N2O that is usually detected in pristine systems.

Seropositivity and history of hospitalisation for dengue in relation to anthropometric indices among Colombian children and adults.

The role of anthropometric status on dengue is uncertain. We investigated the relations between anthropometric characteristics (height, body mass index and waist circumference (WC)) and two dengue outcomes, seropositivity and hospitalisation, in a cross-sectional study of 2038 children (aged 2-15 years) and 408 adults (aged 18-72 years) from Bucaramanga, Colombia. Anthropometric variables were standardised by age and sex in children. Seropositivity was determined through immunoglobulin G antibodies; past hospitalisation for dengue was self-reported. We modelled the prevalence of each outcome by levels of anthropometric exposures using generalised estimating equations with restricted cubic splines. In children, dengue seropositivity was 60.8%; 9.9% of seropositive children reported prior hospitalisation for dengue. WC was positively associated with seropositivity in girls (90th vs. 10th percentile adjusted prevalence ratio (APR) = 1.19; 95% confidence interval (CI) 1.03-1.36). Among adults, dengue seropositivity was 95.1%; 8.1% of seropositive adults reported past hospitalisation. Height was inversely associated with seropositivity (APR = 0.90; 95% CI 0.83-0.99) and with hospitalisation history (APR = 0.19; 95% CI 0.04-0.79). WC was inversely associated with seropositivity (APR = 0.89; 95% CI 0.81-0.98). We conclude that anthropometry correlates with a history of dengue, but could not determine causation. Prospective studies are warranted to enhance causal inference on these questions.

A voxel-wise assessment of growth differences in infants developing autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a phenotypically and etiologically heterogeneous developmental disorder typically diagnosed around 4 years of age. The development of biomarkers to help in earlier, presymptomatic diagnosis could facilitate earlier identification and therefore earlier intervention and may lead to better outcomes, as well as providing information to help better understand the underlying mechanisms of ASD. In this study, magnetic resonance imaging (MRI) scans of infants at high familial risk, from the Infant Brain Imaging Study (IBIS), at 6, 12 and 24 months of age were included in a morphological analysis, fitting a mixed-effects model to Tensor Based Morphometry (TBM) results to obtain voxel-wise growth trajectories. Subjects were grouped by familial risk and clinical diagnosis at 2 years of age. Several regions, including the posterior cingulate gyrus, the cingulum, the fusiform gyrus, and the precentral gyrus, showed a significant effect for the interaction of group and age associated with ASD, either as an increased or a decreased growth rate of the cerebrum. In general, our results showed increased growth rate within white matter with decreased growth rate found mostly in grey matter. Overall, the regions showing increased growth rate were larger and more numerous than those with decreased growth rate. These results detail, at the voxel level, differences in brain growth trajectories in ASD during the first years of life, previously reported in terms of overall brain volume and surface area.

Percentage of reported Covid-19 cases in Colombia: Estimating the true scale of the pandemic

At the outbreak of a virus, data on cases is sparse and commonly severe cases, with a higher probability of a fatal resolution, are detected at a larger rate than mild cases. In addition, in an under-sampling situation, the number of total cases is under-estimated leading to a biased case fatality rate estimation, most likely inflating the virus mortality. In this communication, we present a method to estimate the sub-report in a country that accounts for both the delay time between symptoms onset to death and the countrys demographics. The method is based on the comparison of the corrected case fatality rate (CFR) of the target country with the one of a benchmark country. Using reported data from Instituto Nacional de Salud up to December 28, we utilize our method to provide a comprehensive estimate of the Covid-19 sub-report in Colombia, its regions and some of its cities during 2020.

Update on Dietary Compliance, Nutritional Status, and Neuropsychological Functioning in the Chilean Phenylketonuria cohort

Abstract Since 1992, Chile has had a Newborn Screening Program for Phenylketonuria (PKU), which currently has an incidence of 1:18,916 newborns. The objective of the current study was to describe the 2020 follow up of the Chilean PKU cohort. The variables analyzed were: nutritional status, dietary compliance and neuropsychological functioning. We conducted a descriptive cross-sectional statistical analysis. The 271 subjects with PKU had an average age of diagnosis of 17±8 days and a phenylalanine (Phe) level of 1122±546 umol/L. Approximately 80% of protein requirement came from a protein substitute. For those <18 years of age, 80% had good dietary compliance with Phe level between 120-360 umol/L and those >18 years had a median of 522 umol/L (95%CI 468 - 636). Forty-four percent of the active PKU cohort had overweight/obesity. Eighty-five percent of the cohort >4 years of age had a normal intelligence quotient (IQ) (score 80-120). We observed a negative correlation (p <0.001; 95% CI: - 0.5, -0.2) between IQ score and Phe level. The Chilean protocol and protein substitute subsidy for life, together with the follow-up and continuous education carried out by the clinical team has encouraged compliance.

Psychotic symptoms in COVID-19 patients. A retrospective descriptive study.

Psychotic symptoms have been related to other coronavirus infections. We conducted a single-centre retrospective and observational study to describe new-onset psychotic episodes in COVID-19 patients. Ten patients infected by the novel coronavirus with psychotic symptoms and no previous history of psychosis were identified by the emergency and liaison psychiatry departments. Nine of the cases presented with psychotic symptoms at least two weeks after the first somatic manifestations attributed to COVID-19 and receiving pharmacological treatment. Structured delusions mixed with confusional features were the most frequent clinical presentations. Hence, COVID-19 patients can develop psychotic symptoms as a consequence of multiple concurrent factors.