Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Apunts. Educació física i esports

Resumen tomado de la publicaciónSe realiza una estimación del consumo de oxígeno y un análisis de las demandas energéticas de la esgrima de competición. En asaltos de competición, el consumo de oxígeno estimado en mujeres es inferior al de los hombres. La intensidad individual media se encuentra entre el 56 y el 74 por ciento del Vo subíndice2 max (Vo2max), con máximos entre el 75 y el 99 por ciento del Vo2max, lo que confirma la relevancia de los requerimientos aeróbicos en el esgrima. Las demandas energéticas en la competición internacional son superiores a las registradas en una competición autonómica y al de diferentes situaciones de entrenamiento. Entre tiradores del mismo género no se aprecian diferencias significativas en función del arma. Del análisis en competición se destaca la variabilidad de la respuesta funcional de los esgrimistas dada la influencia de factores como la adaptación cardiocirculatoria individual, importancia de la competición, eliminatoria registrada, nivel del rival, dinámica competitiva arma y género.CataluñaUniversidad Pública de Navarra. Biblioteca; Campus de Arrosadía; 31006 Pamplona; Tel. +34948169060; Fax +34948169069; [email protected]

Apunts. Educació física i esports

Resumen tomado de la publicaciónSe observa que la resistencia específica del jugador tiene una influencia directa sobre el rendimiento en el tenis. Sin embargo, las pruebas utilizadas para valorarla no suelen incluir tareas motrices en situaciones de juego reales. Se pretende desarrollar una prueba de campo de valoración de la resistencia específica en tenis (Specific Endurance Tennis Test, SET-Test), analizando el comportamiento de la frecuencia cardiaca (FC) y de parámetros de efectividad técnica (ET), con el fin de averiguar una posible relación entre ambos parámetros y de éstos con el rendimiento deportivo en jugadores de competición. Participaron siete tenistas masculinos, a los cuales les fue administrada una prueba triangular, progresiva, continua y de intensidad máxima conducida por una máquina lanzapelotas, durante la cual se registró la FC y, al mismo tiempo, parámetros objetivos de ET (precisión y potencia). Se observa un punto de deflexión de la FC (PDFC) en un 86 por ciento de los sujetos estudiados, previo o coincidente con una disminución de la ET (punto de deflexión de la eficiencia técnica, PDET). Se concluye que la prueba propuesta puede ser un método específico y válido para evaluar la resistencia específica y la condición aeróbica en tenistas, aunque se necesitan más estudios para confirmar las hipótesis planteadas y su validez.CataluñaUniversidad Pública de Navarra. Biblioteca; Campus de Arrosadía; 31006 Pamplona; Tel. +34948169060; Fax +34948169069; [email protected]

Prevalencia de trastornos de la conducta alimentaria en deportistas

El objetivo del presente estudio es comparar las puntuaciones en dos pruebas psicométricas.Eating Attitudes Test (Garner y Garfinkel, 1979) y Eating Disorder Inventory (Garner y Olmsted, 1984), de un grupo de deportistas de alto rendimiento, otro de personas físicamente activas y otro de sedentarios. Las mujeres obtuvieron puntuaciones superiores a los hombres en la puntuación EAT y en las subescalas MA, IC, IN, Y P del test EDI. No hay diferencias en ninguna de las puntuaciones de los grupos reseñados de mujeres, mientras que los hombres de alto rendimiento y físicamente activos puntuaron más alto que los sedentarios en el test EAT. En las mujeres aparecen diferencias en las puntuaciones del EAT y en las escalas MA y P del EDI cuando separamos aquellos deportes en los que hay categorías de peso. Sin embargo, esto no ocurre en los hombres. Parece que estos resultados apoyan la idea de que la presión en forma de exigencia de peso y revisiones constantes del mismo, provoca conductas alimentarias anormales y perturbaciones emocionales similares a las de la anorexia y la bulimia. En el caso de las mujeres, el practicar actividad física o hacer deporte de alto nivel parece no aportar unas exigencias definitivas (respecto a las mujeres sedentarias), mientras que el hecho diferencia de xigir un peso determinado, sí que es drástico y hace que emerjan las diferencias reseñadas. Parece en cambio, que los hombres sedentarios no experimentan apenas presión, y los que practican deporte o actividad física sí. Se comentan igualmente las diversas diferencias de criterios clínicos en diferentes gruposThe aim of the present study is to compare the scores of two psychometric tests, EAT (Garner and Garfinkel,1979) and EDi (Garner and Olrnsted, 1984), of a high level athlete's group, a physically active group and sedentary subject's group. Women obtaines higher scores than men in EAT scores and in MA, IC, IN, YP subescales of the EDI test. There is no difference between the former group scores in the case of women. In the other hand, men elite athletes and pysically active men scored higher than sedentary men on the EAT test.If we separate sports by weigth-categories, some diferences occur with the women group on the EAt scores and the EDI subscales MA and P , but this does not happen with the maen's group. Considering these results it looks like the pressure, in terms of weigth exigences and constant weigth revision provoques abnormal alimentary behaviors, and emotional perturbances similar to the anorexia nervosa and bulimia. With women, the fact of practicing physical activity or higth level sports seems not to bring definitive exigencies (with respect to sedentary women), wile the differential fact of the exigence of a special weigth, is drastic and makes appear the mentioned differences. In the other hand, it looks like sedentary men do not experience any pressure, while the men who practice sport or physical activitydo.Different incidencies of clinical criteria for the different groups are as well commente

Prevalencia de trastornos de la conducta alimentaria en deportistas

El objetivo del presente estudio es comparar las puntuaciones en dos pruebas psicométricas.Eating Attitudes Test (Garner y Garfinkel, 1979) y Eating Disorder Inventory (Garner y Olmsted, 1984), de un grupo de deportistas de alto rendimiento, otro de personas físicamente activas y otro de sedentarios. Las mujeres obtuvieron puntuaciones superiores a los hombres en la puntuación EAT y en las subescalas MA, IC, IN, Y P del test EDI. No hay diferencias en ninguna de las puntuaciones de los grupos reseñados de mujeres, mientras que los hombres de alto rendimiento y físicamente activos puntuaron más alto que los sedentarios en el test EAT. En las mujeres aparecen diferencias en las puntuaciones del EAT y en las escalas MA y P del EDI cuando separamos aquellos deportes en los que hay categorías de peso. Sin embargo, esto no ocurre en los hombres. Parece que estos resultados apoyan la idea de que la presión en forma de exigencia de peso y revisiones constantes del mismo, provoca conductas alimentarias anormales y perturbaciones emocionales similares a las de la anorexia y la bulimia. En el caso de las mujeres, el practicar actividad física o hacer deporte de alto nivel parece no aportar unas exigencias definitivas (respecto a las mujeres sedentarias), mientras que el hecho diferencia de xigir un peso determinado, sí que es drástico y hace que emerjan las diferencias reseñadas. Parece en cambio, que los hombres sedentarios no experimentan apenas presión, y los que practican deporte o actividad física sí. Se comentan igualmente las diversas diferencias de criterios clínicos en diferentes gruposThe aim of the present study is to compare the scores of two psychometric tests, EAT (Garner and Garfinkel,1979) and EDi (Garner and Olrnsted, 1984), of a high level athlete's group, a physically active group and sedentary subject's group. Women obtaines higher scores than men in EAT scores and in MA, IC, IN, YP subescales of the EDI test. There is no difference between the former group scores in the case of women. In the other hand, men elite athletes and pysically active men scored higher than sedentary men on the EAT test.If we separate sports by weigth-categories, some diferences occur with the women group on the EAt scores and the EDI subscales MA and P , but this does not happen with the maen's group. Considering these results it looks like the pressure, in terms of weigth exigences and constant weigth revision provoques abnormal alimentary behaviors, and emotional perturbances similar to the anorexia nervosa and bulimia. With women, the fact of practicing physical activity or higth level sports seems not to bring definitive exigencies (with respect to sedentary women), wile the differential fact of the exigence of a special weigth, is drastic and makes appear the mentioned differences. In the other hand, it looks like sedentary men do not experience any pressure, while the men who practice sport or physical activitydo.Different incidencies of clinical criteria for the different groups are as well commente

Increased translation as a novel pathogenic mechanism in Huntington's disease

Huntington's disease is a neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the huntingtin gene. Striatal projection neurons are mainly affected, leading to motor symptoms, but molecular mechanisms involved in their vulnerability are not fully characterized. Here, we show that eIF4E binding protein (4E-BP), a protein that inhibits translation, is inactivated in Huntington's disease striatum by increased phosphorylation. Accordingly, we detected aberrant de novo protein synthesis. Proteomic characterization indicates that translation specifically affects sets of proteins as we observed upregulation of ribosomal and oxidative phosphorylation proteins and downregulation of proteins related to neuronal structure and function. Interestingly, treatment with the translation inhibitor 4EGI-1 prevented R6/1 mice motor deficits, although corticostriatal long-term depression was not markedly changed in behaving animals. At the molecular level, injection of 4EGI-1 normalized protein synthesis and ribosomal content in R6/1 mouse striatum. In conclusion, our results indicate that dysregulation of protein synthesis is involved in mutant huntingtin-induced striatal neuron dysfunction

Dioxin receptor regulates aldehyde dehydrogenase to block melanoma tumorigenesis and metastasis

International audienceAbstractBackgroundThe dioxin (AhR) receptor can have oncogenic or tumor suppressor activities depending on the phenotype of the target cell. We have shown that AhR knockdown promotes melanoma primary tumorigenesis and lung metastasis in the mouse and that human metastatic melanomas had reduced AhR levels with respect to benign nevi.MethodsMouse melanoma B16F10 cells were engineered by retroviral transduction to stably downregulate AhR expression, Aldh1a1 expression or both. They were characterized for Aldh1a1 activity, stem cell markers and migration and invasion in vitro. Their tumorigenicity in vivo was analyzed using xenografts and lung metastasis assays as well as in vivo imaging.ResultsDepletion of aldehyde dehydrogenase 1a1 (Aldh1a1) impairs the pro-tumorigenic and pro-metastatic advantage of melanoma cells lacking AhR expression (sh-AhR). Thus, Aldh1a1 knockdown in sh-AhR cells (sh-AhR + sh-Aldh1a1) diminished their migration and invasion potentials and blocked tumor growth and metastasis to the lungs in immunocompetent AhR+/+ recipient mice. However, Aldh1a1 downmodulation in AhR-expressing B16F10 cells did not significantly affect tumor growth in vivo. Aldh1a1 knockdown reduced the high levels of CD133+/CD29+/CD44+ cells, melanosphere size and the expression of the pluripotency marker Sox2 in sh-AhR cells. Interestingly, Sox2 increased Aldh1a1 expression in sh-AhR but not in sh-AhR + sh-Aldh1a1 cells, suggesting that Aldh1a1 and Sox2 may be co-regulated in melanoma cells. In vivo imaging revealed that mice inoculated with AhR + Aldh1a1 knockdown cells had reduced tumor burden and enhanced survival than those receiving Aldh1a1-expressing sh-AhR cells.ConclusionsAldh1a1 overactivation in an AhR-deficient background enhances melanoma progression. Since AhR may antagonize the protumoral effects of Aldh1a1, the AhRlow-Aldh1a1high phenotype could be indicative of bad outcome in melanoma