The β-catenin-dependent Wnt pathway exerts multiple context-dependent roles in embryonic and adult tissues. In planarians, β-catenin-1 is thought to specify posterior identities through the ...generation of an anteroposterior gradient. However, the existence of such a gradient has not been directly demonstrated. Here, we use a specific polyclonal antibody to demonstrate that nuclear β-CATENIN-1 exists as an anteroposterior gradient from the pre-pharyngeal region to the tail of the planarian Schmidtea polychroa High levels in the posterior region steadily decrease towards the pre-pharyngeal region but then increase again in the head region. During regeneration, β-CATENIN-1 is nuclearized in both anterior and posterior blastemas, but the canonical WNT1 ligand only influences posterior nuclearization. Additionally, β-catenin-1 is required for proper anterior morphogenesis, consistent with the high levels of nuclear β-CATENIN-1 observed in this region. We further demonstrate that β-CATENIN-1 is abundant in developing and differentiated organs, and is particularly required for the specification of the germline. Altogether, our findings provide the first direct evidence of an anteroposterior nuclear β-CATENIN-1 gradient in adult planarians and uncover novel, context-dependent roles for β-catenin-1 during anterior regeneration and organogenesis.
Preoperative anemia is a risk factor for postoperative morbidity and in-hospital mortality in cardiac surgery. However, it is not known whether treatment of anemia before cardiac surgery by ...administering recombinant human erythropoietin (rhEPO) plus iron improves postoperative outcomes and decreases red blood cell transfusions in these patients. In 1998 a collection of consecutive data for patients who underwent valve replacement was initiated and the inclusion criterion was anemia. Treatment with rhEPO was given at a dose of 500 IU/kg/day every week for 4 weeks and the fifth dose 48 hours before valve replacement. During each rhEPO session, patients received intravenous iron sucrose supplementation. The intervention cohort (2006 to 2011) included 75 patients and the observation cohort was composed of 59 patients who did not receive any treatment (1998 to 2005). Multivariable logistic regression analysis showed that administration of combined therapy was independently associated with decreased postoperative morbidity (odds ratio OR 0.13, 95% confidence interval CI 0.03 to 0.59 p = 0.008) and in-hospital mortality (OR 0.16, 95% CI 0.28 to 0.95 p = 0.04) after adjusting for logistic European System for Cardiac Operative Risk Evaluation score, type of intervention, time of cardiopulmonary bypass, and year of surgery. Individually, this treatment also decreased postoperative renal failure (OR 0.23, 95% CI 0.06 to 0.88, p = 0.03). Rate of red blood cell transfusion decreased from 93% in the observation cohort to 67% in the intervention cohort as did days of hospitalization (median, 15 days, 10 to 27, versus 10 days, 8 to 14, respectively, p = 0.01 for all comparisons). In conclusion, administration of intravenous rhEPO plus iron in anemic patients before valve replacement improves postoperative survival, decreases blood transfusions, and shortens hospitalization.
The wnt signaling pathway is an intercellular communication mechanism essential in cell-fate specification, tissue patterning and regional-identity specification. A βcatenin-dependent signal ...specifies the AP (Anteroposterior) axis of planarians, both during regeneration of new tissues and during normal homeostasis. Accordingly, four wnts (posterior wnts) are expressed in a nested manner in central and posterior regions of planarians. We have analyzed the specific role of each posterior wnt and the possible cooperation between them in specifying and patterning planarian central and posterior regions. We show that each posterior wnt exerts a distinct role during re-specification and maintenance of the central and posterior planarian regions, and that the integration of the different wnt signals (βcatenin dependent and independent) underlies the patterning of the AP axis from the central region to the tip of the tail. Based on these findings and data from the literature, we propose a model for patterning the planarian AP axis.
Blood flow (Qb) is one of the dialysis parameters most strongly influencing the performance of dialysis modalities. However, few studies have compared different dialysis modalities in patients with ...low Qb. We conducted a prospective, single‐center study in 21 patients. Each patient underwent four dialysis sessions with routine dialysis parameters: high‐flux hemodialysis (HD), predilution hemodiafiltration (pre‐HDF), expanded HD (HDx), and postdilution HDF (post‐HDF). The removal ratios (RR) of urea, creatinine, ß2‐microglobulin, myoglobin, prolactin, α1‐microglobulin, free kappa and lambda immunoglobulin light chains (ķFLC and λFLC), α1‐acid glycoprotein, and albumin were compared intraindividually. A proportional part of the dialysate was collected to quantify albumin loss. There were no differences in urea and creatinine RRs. The β2‐microglobulin RR was higher in pre‐HDF and post‐HDF. Myoglobin and prolactin RRs were higher with HDx and post‐HDF. The α1‐microglobulin and α1‐acid glycoprotein RRs were significantly higher with post‐HDF than with other treatments, and RRs obtained with HDx were higher than obtained with HD and pre‐HDF. Free ķFLC and λFLC RRs showed the following results in ascending order: HD, pre‐HDF, HDx, and post‐HDF, most of them with statistical significance. Albumin loss varied from 0.45 g with HD to 3.5 g with post‐HDF. The global removal score values were 41.0 ± 4.8% with HD, 44.0 ± 5.2% with pre‐HDF, 49.5 ± 4.6% with HDx, and 54.8 ± 5.3% with post‐HDF, with significant differences between all treatment modalities. In conclusion, this study confirms the superiority of post‐HDF over high‐flux HD, pre‐HDF, and HDx in patients with low Qb. HDx was the closest alternative to post‐HDF and was clearly superior to HD and pre‐HDF. Finally, pre‐HDF was also superior to HD. With this Qb, there was a higher risk of underdialysis, both diffusive and convective, especially in patients with a session duration of less than 5 h.
The sodium gradient during hemodialysis sessions is one of the key factors in sodium balance in patients with dialysis-dependent chronic kidney disease; however, until the appearance of the new ...monitors with sodium modules, the differences between prescribed and measured sodium have been understudied. The present study aimed to compare the impact on the measured conductivity and the initial and final plasma sodium after changing the 5008 Cordiax to the new 6008 Cordiax monitor.
106 patients on hemodialysis were included. Each patient underwent 2 dialysis sessions in which only the monitor was varied. The variables collected were dialysate, sodium and bicarbonate prescribed, real conductivity, initial and final plasma sodium measured, and the calculated sodium gradient (ΔPNa).
The change of dialysis monitor showed small but statistically significant differences in the initial (138.14mmol/L with 5008 vs. 138.81mmol/L with 6008) and final plasma sodium (139.58mmol/L vs. 140.97mmol/L), as well as in the actual conductivity obtained (13.97 vs. 14.1mS/cm). The ΔPNa also increased significantly.
The change from 5008 to 6008 monitor is associated with increased conductivity, leading the patient to end the sessions with higher plasma sodium and ΔPNa. Knowing and confirming this change will allow us to individualize the sodium prescription and avoid possible undesirable effects. It could be the preliminary study to explore the new sodium biosensor incorporated into the new generation of monitors.
El gradiente de sodio durante las sesiones es uno de los factores clave en el balance de este ion en los pacientes en hemodiálisis; sin embargo, hasta la aparición de los nuevos monitores con módulos de sodio, las diferencias entre el sodio prescrito y el medido han sido poco estudiadas. El objetivo del presente estudio fue comparar el impacto del cambio del monitor 5008 Cordiax al nuevo monitor 6008 Cordiax sobre los resultados de la conductividad real medida, del sodio plasmático inicial y final.
Se incluyeron 106 pacientes en hemodiálisis. Cada paciente recibió 2 sesiones de diálisis en la que solo se varió el monitor. Las variables recogidas fueron: el concentrado, sodio y bicarbonato prescritos, conductividad real, sodio plasmático inicial y final medidos por dialisancia iónica y se calculó el cambio de la concentración de sodio plasmático durante el tratamiento o delta de sodio (ΔPNa).
El cambio de monitor de diálisis mostró pequeñas diferencias, aunque significativas, en el sodio plasmático inicial (138.14mmol/L con 5008 vs 138.81mmol/L con 6008) y final (139.58mmol/L vs 140.97mmol/L), así como en la conductividad real obtenida (13,97 vs 14,10mS/cm). El ΔPNa también aumento significativamente.
El cambio de monitor 5008 a 6008 se asocia a un aumento en la conductividad, un sodio plasmático más elevado y un incremento en el ΔPNa. El conocer y confirmar este cambio permitirá individualizar la prescripción de sodio, evitar posibles efectos indeseables y podría ser el estudio preliminar para explorar el nuevo biosensor de control de sodio incorporado en la nueva generación de monitores.
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El gradiente de sodio durante las sesiones es uno de los factores clave en el balance de este ion en los pacientes en hemodiálisis; sin embargo, hasta la aparición de los nuevos ...monitores con módulos de sodio, las diferencias entre el sodio prescrito y el medido han sido poco estudiadas. El objetivo del presente estudio fue comparar el impacto del cambio del monitor 5008 Cordiax al nuevo monitor 6008 Cordiax sobre los resultados de la conductividad real medida, del sodio plasmático inicial y final.
Se incluyeron 106 pacientes en hemodiálisis. Cada paciente recibió dos sesiones de diálisis en las que solo se varió el monitor. Las variables recogidas fueron: el concentrado, sodio y bicarbonato prescritos, conductividad real, sodio plasmático inicial y final medidos por dialisancia iónica y se calculó el cambio de la concentración de sodio plasmático durante el tratamiento o delta de sodio (ΔPNa).
El cambio de monitor de diálisis mostró pequeñas diferencias, aunque significativas, en el sodio plasmático inicial (138,14 mmol/L con 5008 vs. 138,81 mmol/L con 6008) y final (139,58 mmol/L vs. 140,97 mmol/L), así como en la conductividad real obtenida (13,97 vs. 14,10 mS/cm). El ΔPNa también aumento significativamente.
El cambio de monitor 5008 a 6008 se asocia a un aumento en la conductividad, un sodio plasmático más elevado y un incremento en el ΔPNa. El conocer y confirmar este cambio permitirá individualizar la prescripción de sodio, evitar posibles efectos indeseables y podría ser el estudio preliminar para explorar el nuevo biosensor de control de sodio incorporado en la nueva generación de monitores.
The sodium gradient during hemodialysis sessions is one of the key factors in sodium balance in patients with dialysis-dependent chronic kidney disease; however, until the appearance of the new monitors with sodium modules, the differences between prescribed and measured sodium have been understudied. The present study aimed to compare the impact on the measured conductivity and the initial and final plasma sodium after changing the 5008 Cordiax to the new 6008 Cordiax monitor.
106 patients on hemodialysis were included. Each patient underwent 2 dialysis sessions in which only the monitor was varied. The variables collected were dialysate, sodium and bicarbonate prescribed, real conductivity, initial and final plasma sodium measured, and the calculated sodium gradient (ΔPNa).
The change of dialysis monitor showed small but statistically significant differences in the initial (138.14 mmol/L with 5008 vs. 138.81 mmol/L with 6008) and final plasma sodium (139.58 mmol/L vs. 140.97 mmol/L), as well as in the actual conductivity obtained (13.97 vs. 14.1 mS/cm). The ΔPNa also increased significantly.
The change from 5008 to 6008 monitor is associated with increased conductivity, leading the patient to end the sessions with higher plasma sodium and ΔPNa. Knowing and confirming this change will allow us to individualize the sodium prescription and avoid possible undesirable effects. It could be the preliminary study to explore the new sodium biosensor incorporated into the new generation of monitors.
Silent atrial fibrillation (AF) may be the cause of some cryptogenic strokes (CrS). The aim of the study was to analyse atrial size and function by speckle tracking echocardiography in CrS patients ...to detect atrial disease. Patients admitted to the hospital due to CrS were included prospectively. Echocardiogram analysis included left atrial ejection fraction (LAEF) and atrial strain. Insertable cardiac monitor was implanted, and AF was defined as an episode of ≥1 min in the first year after stroke. Left atrial enlargement was defined as indexed volume > 34 mL/m2. Seventy-five consecutive patients were included, aged 76 ± 9 years (arterial hypertension 75%). AF was diagnosed in 49% of cases. The AF group had higher atrial volume and worse atrial function: peak atrial longitudinal strain (PALs) 19.6 ± 5.7% vs. 29.5 ± 7.2%, peak atrial contraction strain (PACs) 8.9 ± 3.9% vs. 16.5 ± 6%, LAEF 46.8 ± 11.5% vs. 60.6 ± 5.2%; p < 0.001. AF was diagnosed in 20 of 53 patients with non-enlarged atrium, and in 18 of them, atrial dysfunction was present. The multivariate logistic regression analysis demonstrated an independent association between detection of AF and atrial volume, LAEF, and strain. Cut-off values were obtained: LAEF < 55%, PALs < 21.4%, and PACs < 12.9%. In conclusion, speckle tracking echocardiography in CrS patients improves silent atrial disease diagnosis, with or without atrial enlargement.
An organizer is defined as a group of cells that secrete extracellular proteins that specify the fate of surrounding cells according to their concentration. Their function during embryogenesis is key ...in patterning new growing tissues. Although organizers should also participate in adult development when new structures are regenerated, their presence in adults has only been identified in a few species with striking regenerative abilities, such as planarians. Planarians provide a unique model to understand the function of adult organizers, since the presence of adult pluripotent stem cells provides them with the ability to regenerate any body part. Previous studies have shown that the differential activation of the WNT/β-catenin signal in each wound is fundamental to establish an anterior or a posterior organizer in the corresponding wound. Here, we identify the receptors that mediate the WNT/β-catenin signal in posterior-facing wounds. We found that Wnt1-Fzd1-LRP5/6 signaling is evolutionarily conserved in executing a WNT/β-catenin signal to specify cell fate and to trigger a proliferative response. Our data allow a better understanding of the mechanism through which organizers signal to a "competent" field of cells and integrate the patterning and growth required during de novo formation of organs and tissues.
Planarians are flatworms with almost unlimited regenerative abilities, which make them an excellent model for stem cell-based regeneration. To study the process of regeneration at the cellular level, ...immunohistochemical staining methods are an important tool, and the availability of such protocols is one of the prerequisites for mechanistic experiments in any animal model. Here, we detail protocols for paraffin embedding and immunostaining of paraffin sections of the model species Schmidtea mediterranea. This protocol yields robust results with a variety of commercially available antibodies. Further, the procedures provide a useful starting point for customizing staining procedures for new antibodies and/or different planarian species.
Recientemente se han desarrollado dializadores de helixona de nueva generación como parte del esfuerzo continuo para mejorar la biocompatibilidad del dializador y evitar reacciones adversas a los ...dializadores sintéticos. Este estudio tuvo como objetivo evaluar el rendimiento y la pérdida de albúmina de esta nueva serie de dializadores en hemodiafiltración y compararla con dializadores de helixona de la generación anterior.
Se realizó un estudio prospectivo en 19 pacientes. Cada paciente recibió ocho sesiones de diálisis con los mismos parámetros de diálisis de rutina; solo varió el dializador: FX60 CorDiax, FX CorAL 60, FX600 CorDiax, FX CorAL 600, FX80 CorDiax, FX CorAL 80, FX800 CorDiax y FX CorAL 800. Los índices de reducción (RR) de urea, creatinina, β2-microglobulina, mioglobina, cadenas ligeras kappa (κFLC), prolactina, α1-microglobulina, α1-glicoproteína ácida, cadenas ligeras lambda (λFLC) y albúmina se compararon intraindividualmente. También se midió la pérdida de albúmina del dializado.
Todos los tratamientos fueron bien tolerados. La media de líquido de reposición osciló entre 31 y 34litros. La comparación de los tratamientos de diálisis no mostró diferencias entre moléculas pequeñas e incluso del tamaño de las β2-microglobulinas. Se encontraron pocas diferencias entre los RR de mioglobina, κFLC, prolactina, α1-microglobulina y λFLC. Las pérdidas de albúmina en el dializado fueron similares, con menos de 2,5gramos por sesión. El dializador FX80 CorDiax mostró puntuaciones de eliminación global ligeramente más altas que el resto de los evaluados, a excepción del FX CorAL 800.
La nueva generación de dializadores de helixona, actualizada para minimizar el riesgo de reacciones adversas, ha mantenido la eficacia y la pérdida de albúmina conseguidas por la generación de helixona previa.
New generation helixone dialyzers has recently been developed as part of the ongoing effort to improve dialyzer hemocompatibility and avoid adverse reactions to synthetic dialyzers. This study aimed to assess the performance and albumin loss of this new dialyzer series in hemodiafiltration and compare it with the previous generation helixone series.
A prospective study was conducted in 19 patients. Each patient underwent eight dialysis sessions with the same routine dialysis parameters; only the dialyzer varied: FX60 CorDiax, FX CorAL 60, FX600 CorDiax, FX CorAL 600, FX80 CorDiax, FX CorAL 80, FX800 CorDiax, and FX CorAL 800. The reduction ratios (RR) of urea, creatinine, β2-microglobulin, myoglobin, kappa-free immunoglobulin light chains (κFLC), prolactin, α1-microglobulin, α1-acid glycoprotein, lambda immunoglobulin light chains (λFLC), and albumin were compared intra-individually. Dialysate albumin loss was also measured.
All treatments were well tolerated. The mean amount of replacement fluid ranged from 31 to 34litres. Comparison of dialysis treatments showed no differences between small molecules and even up to those the size of β2-microglobulins. Little differences were found between myoglobin, κFLC, prolactin, α1-microglobulin, and λFLC RRs, and only FX80 CorDiax was slightly superior to the others. Mean dialysate albumin losses were similar, with less than 2.5grams lost in each dialyzer. The FX80 CorDiax showed slightly higher global removal scores than the other dialyzers evaluated, except for FX CorAL 800.
The new generation helixone dialyzers series has been updated to minimise the risk of adverse reactions, while maintaining the effectiveness and albumin loss achieved by the previous most advanced helixone generation.
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