CaMKII inhibitor 1 (CaMK2N1) mRNA is upregulated following LTP induction in hippocampal slices.

CaMK2N1 and CaMK2N2 (also known as CaMKIINα and ß) are endogenous inhibitors of calcium/calmodulin-dependent kinase II (CaMKII), an enzyme critical for memory and long-term potentiation (LTP), a form of synaptic plasticity thought to underlie learning. CaMK2N1/2 mRNAs are rapidly and differentially upregulated in the hippocampus and amygdala after acquisition or retrieval of fear memory. Moreover, CaMK2N2 protein levels increase after contextual fear conditioning. Therefore, it was proposed that CaMK2N1/2 genes (Camk2n1/2) could be immediate-early genes transcribed promptly (30-60 min) after training. As a first approach to explore a role in synaptic plasticity, we assessed a possible regulation of Camk2n1/2 during the expression phase of LTP in hippocampal CA3-CA1 connections in rat brain slices. Quantitative PCR revealed that Camk2n1, but not Camk2n2, is upregulated 60 min after LTP induction by Schaffer collaterals high-frequency stimulation. We observed a graded, significant positive correlation between the magnitude of LTP and Camk2n1 change in individual slices, suggesting a coordinated regulation of these properties. If mRNA increment actually resulted in the protein upregulation in plasticity-relevant subcellular locations, CaMK2N1 may be involved in CaMKII fine-tuning during LTP maintenance or in the regulation of subsequent plasticity events (metaplasticity).

Resistance of CAD/CAM composite resin and ceramic occlusal veneers to fatigue and fracture in worn posterior teeth: A systematic review.

Severe tooth wear is related to substantial loss of tooth structure, with dentin exposure and significant loss (≥1/3) of the clinical crown. The objective of this systematic review was to summarize and analyze the scientific evidence regarding the mechanical performance of computer-aided design/computer-aided manufacturing (CAD/CAM) composite resin and CAD/CAM lithium disilicate ceramic occlusal veneers, in terms of fatigue and fracture resistance, on severely worn posterior teeth. Currently, occlusal veneers are an alternative for treating worn posterior teeth. Although scientific evidence demonstrates the good performance of lithium disilicate occlusal veneers, there are less brittle materials with a modulus of elasticity more similar to dentin than ceramics, such as resin CAD/CAM blocks. Therefore, it is important to identify which type of material is best for restoring teeth with occlusal wear defects and which material can provide better clinical performance. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of the PubMed, Embase, Web of Science, Scopus, Cochrane, OpenGrey, Redalyc, DSpace, and Grey Literature Report databases was conducted and supplemented by a manual search, with no time or language limitations, until January 2022. We aimed to identify studies evaluating the fatigue and fracture resistance of CAD/CAM composite resin and ceramic occlusal veneers. The quality of the full-text articles was evaluated according to the modified Consolidated Standards of Reporting Trials (CONSORT) criteria for in vitro studies, and 400 articles were initially identified. After removing duplicates and applying the selection criteria, 6 studies were included in the review. The results demonstrated that the mechanical performance of CAD/CAM composite resin occlusal veneers is comparable to that of CAD/CAM lithium disilicate occlusal veneers in terms of fatigue and fracture resistance.

Influence of peritoneal residual volume on the results of the peritoneal equilibration test. Prospective study.

BACKGROUND: Categorization of the capacity of ultrafiltration during a peritoneal equilibration test (PET) is a usual step during the monitoring of peritoneal transport characteristics of Peritoneal Dialysis (PD) patients. Quantifying the peritoneal residual volume (Vr) after the dwell preceding the PET (Vrpre) and at the end of the test (Vrpost) could help to improve the accuracy of the estimation of this variable. METHOD: Following a prospective design, we calculated Vrpre and Vrpost in 116 patients, incident or prevalent on DP, who underwent one or two (n = 27) PET with 3,86/4,25% glucose-based PD solutions and complete drainage at 60 min. We evaluated the consistency of Vr by comparing Vrpre and Vrpost, as also these two parameters in repeated tests. We scrutinized potential associations between demographic and clinical factors, on one side, and the amount of Vr on the other, as also the impact of correcting ultrafiltration during PET for Vr on the categorization of the capacity of ultrafiltration. RESULTS: As a mean, Vrpost was larger than Vrpre. Consequently, correction of ultrafiltration for Vr resulted in significantly higher values than those obtained according to the standard procedure (494 vs. 449 mL, p < 0,0005). We disclosed marked inconsistencies for different estimations of Vr in the same patients (Vrpre vs Vrpost and repeated PET studies). Moreover, no demographic or clinical variable was able to predict the amount of Vr. We observed a significant deviation (>200 mL) between both methods of estimation of the capacity of utrafiltration in only 12,9% of the patients. However, 21,1% of the patients categorized as cases of ultrafiltration failure according to the standard procedure did not maintain this condition after correction for Vr. CONCLUSIONS: Correction for Vr of the capacity of ultrafiltration during a PET carries, as a mean, a minor impact on the categorization of this parameter. However, the results of the test can be significantly affected in 12,9% of the cases. We have been unable to detect demographic or clinical predictors of Vr, which suggests a random component for the mechanics of single peritoneal exchanges. We suggest that Vr should be estimated at the time of categorizing the capacity of ultrafiltration, whenever inconsistencies during serial PET studies are detected.

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. STUDY DESIGN: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). RESULTS: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242-128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. CONCLUSIONS: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. STUDY DESIGN: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). RESULTS: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242-128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. CONCLUSIONS: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.

Influencia del volumen peritoneal residual en los resultados de la prueba de equilibrio peritoneal. Estudio prospectivo / Influence of peritoneal residual volume on the results of the peritoneal equilibration test. Prospective study

Introducción y objetivos: La categorización de la capacidad de ultrafiltración durante la prueba de equilibrio peritoneal (PEP) es parte habitual de la monitorización del funcionalismo peritoneal en pacientes tratados con diálisis peritoneal (DP). La estimación del volumen residual (Vr) tras el cambio previo (Vrpre) y el de la propia PEP (Vrpost) podría ayudar a mejorar la precisión de la prueba. Método: Siguiendo un diseño prospectivo, estimamos el Vrpre y Vrpost en 116 pacientes incidentes o prevalentes en DP que fueron sometidos a una o dos (n=27) PEP con solución de glucosa al 3,86/4,25% y drenaje completo a los 60 minutos. Valoramos la consistencia del Vr comparando Vrpre y Vrpost y también estos parámetros en PEP sucesivas. Analizamos la posible influencia de factores demográficos y clínicos en la cuantía del Vr, así como el impacto de la corrección para Vr de la ultrafiltración durante la PEP sobre la categorización de la capacidad de ultrafiltración. Resultados: El Vrpost fue mayor que el Vrpre, por lo que la ultrafiltración corregida para Vr fue signficativamente mayor que la calculada por procedimiento estándar (494 vs. 449mL, p<0,0005). Resultó notable la escasa concordancia de estimaciones sucesivas (Vrpre vs Vrpost y PEP sucesivas) del Vr. Asimismo, ningún parámetro demográfico o clínico escrutado mostró asociación con la magnitud del Vr. Tan solo un 12,9% de los pacientes presentó una desviación clínicamente significativa (>200mL) de la ultrafiltración corregida para Vr frente al valor estándar. Sin embargo, un 21,1% de los pacientes que cumplían criterio de fallo de ultrafiltración por método estándar, no lo hacían si se aplicaba la corrección para Vr. (AU)

Background: Categorization of the capacity of ultrafiltration during a peritoneal equilibration test (PET) is a usual step during the monitoring of peritoneal transport characteristics of peritoneal dialysis (PD) patients. Quantifying the peritoneal residual volume (Vr) after the dwell preceding the PET (Vrpre) and at the end of the test (Vrpost) could help to improve the accuracy of the estimation of this variable. Method: Following a prospective design, we calculated Vrpre and Vrpost in 116 patients, incident or prevalent on DP, who underwent one or two (n=27) PET with 3.86/4.25% glucose-based PD solutions and complete drainage at 60min. We evaluated the consistency of Vr by comparing Vrpre and Vrpost, as also these two parameters in repeated tests. We scrutinized potential associations between demographic and clinical factors, on one side, and the amount of Vr on the other, as also the impact of correcting ultrafiltration during PET for Vr on the categorization of the capacity of ultrafiltration. Results: As a mean, Vrpost was larger than Vrpre. Consequently, correction of ultrafiltration for Vr resulted in significantly higher values than those obtained according to the standard procedure (494 vs 449mL, p<0.0005). We disclosed marked inconsistencies for different estimations of Vr in the same patients (Vrpre vs Vrpost and repeated PET studies). Moreover, no demographic or clinical variable was able to predict the amount of Vr. We observed a significant deviation (>200mL) between both methods of estimation of the capacity of utrafiltration in only 12.9% of the patients. However, 21.1% of the patients categorized as cases of ultrafiltration failure according to the standard procedure did not maintain this condition after correction for Vr. (AU)

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy / Predictores de eventos clínicos en una cohorte de pacientes con enfermedad de Fabry en tratamiento sustitutivo enzimático

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. Study design: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24–120). Results: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242–128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. Conclusions: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. (AU)

El objetivo de este estudio es realizar un mapa del tratamiento actual de la enfermedad de Fabry en España, analizando el efecto de diferentes factores en el desarrollo de eventos clínicos a largo plazo. Diseño del estudio: Análisis observacional retrospectivo multicéntrico. Criterios de inclusión: pacientes diagnosticados y tratados de enfermedad de Fabry. Se recogieron datos generales en relación con el diagnóstico, síntomas y tipo mutación, tipo de tratamiento recibido, evolución renal y cardiológica. Durante un tiempo de seguimiento de 60 meses (24-120), se recogió el primer evento clínico tras el inicio de tratamiento sustitutivo enzimático definido como mortalidad, evento renal, cardiológico o neurológico. Resultados: Se incluyeron 69 pacientes (42 H, 27 M) con una edad media de 44,6±13,7 años. A los cinco años de tratamiento, el FGe y la hipertrofia ventricular izquierda se mantuvieron estables, y la albuminuria tiende a disminuir, siendo este descenso más significativo en el grupo de pacientes tratados con beta-galactosidasa (de 242 a 128mg/g (p=0,05). Veintiún pacientes sufrieron un evento clínico (30%): seis renales, dos neurológicos y 13 cardiológicos (incluidas tres muertes). Los pacientes con ERC (FGe<60) antes del inicio de tratamiento tuvieron más eventos (log-rank 12.423, p=0,001), manteniéndose la predicción si excluíamos los eventos renales (log-rank 4.086 (p=0,043) en hombres y mujeres. La peor función renal al inicio del tratamiento aumentó entre tres y siete veces el riesgo de eventos clínicos en diferentes modelos de Cox ajustados. Conclusiones: La función renal al inicio de tratamiento sustitutivo enzimático es la principal predictora de desarrollo de eventos clínicos a largo plazo, tanto en hombres como mujeres. El inicio de tratamiento sustitutivo enzimático precoz antes del desarrollo de ERC mejoraría el pronóstico. (AU)