Endothelial deletion of Wt1 disrupts coronary angiogenesis and myocardium development.

Wt1 encodes a zinc finger protein that is crucial for epicardium development. Although WT1 is also expressed in coronary endothelial cells (ECs), the abnormal heart development observed in Wt1 knockout mice is mainly attributed to its functions in the epicardium. Here, we have generated an inducible endothelial-specific Wt1 knockout mouse model (Wt1KOΔEC). Deletion of Wt1 in ECs during coronary plexus formation impaired coronary blood vessels and myocardium development. RNA-Seq analysis of coronary ECs from Wt1KOΔEC mice demonstrated that deletion of Wt1 exerted a major impact on the molecular signature of coronary ECs and modified the expression of several genes that are dynamically modulated over the course of coronary EC development. Many of these differentially expressed genes are involved in cell proliferation, migration and differentiation of coronary ECs; consequently, the aforementioned processes were affected in Wt1KOΔEC mice. The requirement of WT1 in coronary ECs goes beyond the initial formation of the coronary plexus, as its later deletion results in defects in coronary artery formation. Through the characterization of these Wt1KOΔEC mouse models, we show that the deletion of Wt1 in ECs disrupts physiological blood vessel formation.

Deletion of Wt1 during early gonadogenesis leads to differences of sex development in male and female adult mice.

Assessing the role of the WT1 transcription factor (WT1) during early gonad differentiation and its impact on adult sex development has been difficult due to the complete gonadal agenesis and embryonic lethality exhibited by Wt1KO mouse models. Here, we generated Wt1LoxP/GFP;Wt1Cre mice, the first Wt1KO mouse model that reaches adulthood with a dramatically reduced Wt1 expression during early gonadogenesis. Wt1LoxP/GFP;Wt1Cre mice lacked mature gonads and displayed genital tracts containing both male and female genital structures and ambiguous genitalia. We found that WT1 is necessary for the activation of both male and female sex-determining pathways, as embryonic mutant gonads failed to upregulate the expression of the genes specific for each genetic programme. The gonads of Wt1LoxP/GFP;Wt1Cre mice showed a lack of production of Sertoli and pre-granulosa cells and a reduced number of germ cells. NR5A1 and the steroidogenic genes expression was modulated differently in XY and XX Wt1LoxP/GFP;Wt1Cre gonads, explaining the mutant phenotypes. Further studies of the XX Wt1LoxP/GFP;Wt1Cre gonads revealed that deletion of WT1 at an early stage impaired the differentiation of several cell types including somatic cells and the ovarian epithelium. Through the characterisation of this Wt1KO mouse model, we show that the deletion of Wt1 during early gonadogenesis produces dramatic defects in adult sex development.

Antithyroid antibodies as a potential marker of autoimmune-mediated late onset temporal lobe epilepsy.

UNLABELLED: In one third of patients with epilepsy starting in adulthood the aetiology remains undetermined. Some patients with late onset temporal lobe epilepsy (TLE) together with memory decline have elevated antithyroid antibodies. PURPOSE: To compare the prevalence of antithyroid antibodies (aTR-ab) in adult onset temporal lobe epilepsy (TLE) patients with known and unknown TLE aetiology (N=42). Moreover, the sera of these patients was also assayed for antinuclear antibodies (ANA), anticardiolipin antibodies (ACL), anti glutamic acid decarboxylase antibodies (GAD) and antiglidadin antibodies. RESULTS: Positive aTR-ab in the sera of patients with unknown aetiology was 11/23 (47.8%) vs. 1/19 (4.3%) in the group with known aetiology (p=0.005). In 9/11 (81%) a pre-existing autoimmune disease was confirmed. Nine (81%) were women and five (45%) had memory impairment. There were 5/11 (45%) pharmacoresistant patients, and corticosteroid treatment was initiated in 3/5 with cognitive and seizure improvement. The results of other immunological tests were only remarkable for antiGAD antibodies with 3/11 (27%) positive patients, but this subgroup does not have any significant clinical differential feature. CONCLUSIONS: Late-onset TLE with positive aTR-ab tends to be middle-aged women with nonpharmacoresistant cryptogenic epilepsy plus cognitive decline and other associated autoimmune diseases. It could be advisable to test aTR-ab in TLE patients with an unknown aetiology, in order to improve diagnosis and resulting treatment.

Prevalencia de úlceras por presión en atención primaria en dos comarcas catalanas / Prevalence of pressure sores in primary care in two areas of Catalonia (Spain)

Objetivo. Conocer la prevalencia de deterioro de la integridad cutánea por úlceras por presión, y su riesgo. Método. Se presenta un estudio observacional transversal, realizado entre el 1 y el 15 de abril de 2003, que comprende a todas las enfermeras comunitarias de las comarcas del Bages y del Berguedà (Barcelona) y a una enfermera responsable de cada residencia geriátrica. Se recogió información (características del paciente, cuidador y medidas preventivas) de los casos diagnosticados previamente de deterioro de la integridad cutánea y de riesgo de deterioro de la integridad cutánea. Resultados. Se estudiaron 810 casos: 209 de deterioro de la integridad cutánea y 601 de riesgo de deterioro de la integridad cutánea. La prevalencia del deterioro de la integridad cutánea por úlceras por presión fue del 0,11% entre la población adulta y del 0,42% en mayores de 64 años, y del 7,3% en pacientes de atención domiciliaria y del 4,8% en residentes de residencias geriátricas. A cada enfermera comunitaria le correspondieron, de media, 3,7 pacientes (desviación estándar [DE] = 2,5) con riesgo de deterioro de la integridad cutánea y 1,8 (DE = 1,1) con presencia de úlceras por presión. Conclusiones. Dada la prevalencia de úlceras por presión en los pacientes de atención domiciliaria, es necesario aumentar la detección del riesgo para evitar el proceso ulceroso, aumentar las medidas preventivas en las situaciones de riesgo detectadas, y mejorar la educación sanitaria a familiares cuidadores que tanto intervienen en el proceso

Objective. To determine the prevalence of and risk factors for skin breakdown due to pressure ulcers. Method. We performed an observational, cross sectional study between April 1 and April 15, 2003 in all community nurses in the areas of Bages and Berguedà (Barcelona, Spain) and the head nurses of all nursing homes. Information (patient and caregiver characteristics and preventive measures) was gathered on all patients previously diagnosed with skin breakdown or risk of skin breakdown. Results. A total of 810 patients were studied (209 with skin breakdown and 601 at risk for skin breakdown). The prevalence of patients with skin breakdown due to pressure ulcers was 0.11% among the adult population, 0.42% in individuals aged more than 64 years old, 7.3% in patients receiving home care, and 4.8% in nursing home residents. Each community nurse attended a mean of 3.7 patients (SD = 2.5) at risk of skin breakdown and a mean of 1.8 patients (SD = 1.1) with pressure ulcers. Conclusions. Given the prevalence of pressure ulcers in patients receiving home care, detection of risk should be increased to prevent ulcer progression. When risk is detected, preventive measures should be increased. Health education should be improved in family caregivers, who play a major role in the process