A Neuroligin-1 mutation associated with Alzheimer's disease produces memory and age-dependent impairments in hippocampal plasticity.

Alzheimer's disease (AD) is characterized by memory impairments and age-dependent synapse loss. Experimental and clinical studies have shown decreased expression of the glutamatergic protein Neuroligin-1 (Nlgn1) in AD. However, the consequences of a sustained reduction of Nlgn1 are unknown. Here, we generated a knockin mouse that reproduces the NLGN1 Thr271fs mutation, identified in heterozygosis in a familial case of AD. We found that Nlgn1 Thr271fs mutation abolishes Nlgn1 expression in mouse brain. Importantly, heterozygous Nlgn1 Thr271fs mice showed delay-dependent amnesia for recognition memory. Electrophysiological recordings uncovered age-dependent impairments in basal synaptic transmission and long-term potentiation (LTP) in CA1 hippocampal neurons of heterozygous Nlgn1 Thr271fs mice. In contrast, homozygous Nlgn1 Thr271fs mice showed impaired fear-conditioning memory and normal basal synaptic transmission, suggesting unshared mechanisms for a partial or total loss of Nlgn1. These data suggest that decreased Nlgn1 may contribute to the synaptic and memory deficits in AD.

C1-C2 Rotatory Subluxation in Adults "A Narrative Review".

The atlantoaxial joint C2 (axis) with the anterior arch of C1 (atlas) allows 50% of cervical lateral rotation. It is responsible for precise and important movements that allow us to perform precise actions, both in normal and working life. Due to low incidence in adults, this condition often goes undiagnosed, or the diagnosis is delayed and the outcome is worse. An early diagnosis and treatment are essential to ensure satisfactory neurological and functional outcomes. The aim of this review is to analyze C1-C2 rotatory subluxation in adults, given its rarity. The time between injury and reduction is key, as it is directly related to prognosis and the severity of the treatment options. Due to low incidence in adults, this condition often goes undiagnosed, or the diagnosis is delayed as a lot of cases are not related to a clear trauma, with a poor prognosis just because of the late diagnosis and the outcome is worse. The correct approach and treatment of atlantoaxial dislocation requires a careful study of the radiological findings to decide the direction and plane of the dislocation, and the search for associated skeletal anomalies.

Restoration in Vertebral Compression Fractures (VCF): Effectiveness Evaluation Based on 3D Technology.

There are few studies about anatomical reduction of the fractured vertebral body before stabilization for treatment of vertebral compression fracture (VCF). Although restoration on vertebral height has been useful, the reduction of fractured endplates is limited. The vertebra is part of a joint, and vertebral endplates must be treated like other weight-bearing joint to avoid complications. The aim of this study was to evaluate the feasibility of anatomic reduction of vertebral compression fracture, in different bone conditions, fracture types, and ages (VCF). Under methodological point of view, we followed different steps: first was the placement of two expandable titanium implants just below the fracture. Later, to push the fractured endplates into a more anatomical position, the implants were expanded. Finally, with the implants perfectly positioned, PMMA cement was injected to avoid any loss of correction. To evaluate the effectiveness of this procedure in anatomical fracture reduction, a method based on 3D CT reconstructions was developed. In this paper, we have developed the procedure in three case studies. In all of them, we were able to demonstrate the efficacy of this procedure to reduce the VCF. The percentage of correction of the kyphotic angle varied range between 49% and 62% with respect to the value after the fracture preoperative value. This was accompanied by a reduction of the pain level on the VAS scale around 50%. In conclusion, this novel approach to the vertebral fracture treatment (VCF) associated with 3D assessment have demonstrated the possibility of reducing the vertebral kyphosis angle and the vertebral endplate fractures. However, given the few cases presented, more studies are necessaries to confirm these results.

Selective expression of the neurexin substrate for presenilin in the adult forebrain causes deficits in associative memory and presynaptic plasticity.

Presenilins (PS) form the active subunit of the gamma-secretase complex, which mediates the proteolytic clearance of a broad variety of type-I plasma membrane proteins. Loss-of-function mutations in PSEN1/2 genes are the leading cause of familial Alzheimer's disease (fAD). However, the PS/gamma-secretase substrates relevant for the neuronal deficits associated with a loss of PS function are not completely known. The members of the neurexin (Nrxn) family of presynaptic plasma membrane proteins are candidates to mediate aspects of the synaptic and memory deficits associated with a loss of PS function. Previous work has shown that fAD-linked PS mutants or inactivation of PS by genetic and pharmacological approaches failed to clear Nrxn C-terminal fragments (NrxnCTF), leading to its abnormal accumulation at presynaptic terminals. Here, we generated transgenic mice that selectively recreate the presynaptic accumulation of NrxnCTF in adult forebrain neurons, leaving unaltered the function of PS/gamma-secretase complex towards other substrates. Behavioral characterization identified selective impairments in NrxnCTF mice, including decreased fear-conditioning memory. Electrophysiological recordings in medial prefrontal cortex-basolateral amygdala (mPFC-BLA) of behaving mice showed normal synaptic transmission and uncovered specific defects in synaptic facilitation. These data functionally link the accumulation of NrxnCTF with defects in associative memory and short-term synaptic plasticity, pointing at impaired clearance of NrxnCTF as a new mediator in AD.

BLASSO: integration of biological knowledge into a regularized linear model.

BACKGROUND: In RNA-Seq gene expression analysis, a genetic signature or biomarker is defined as a subset of genes that is probably involved in a given complex human trait and usually provide predictive capabilities for that trait. The discovery of new genetic signatures is challenging, as it entails the analysis of complex-nature information encoded at gene level. Moreover, biomarkers selection becomes unstable, since high correlation among the thousands of genes included in each sample usually exists, thus obtaining very low overlapping rates between the genetic signatures proposed by different authors. In this sense, this paper proposes BLASSO, a simple and highly interpretable linear model with l1-regularization that incorporates prior biological knowledge to the prediction of breast cancer outcomes. Two different approaches to integrate biological knowledge in BLASSO, Gene-specific and Gene-disease, are proposed to test their predictive performance and biomarker stability on a public RNA-Seq gene expression dataset for breast cancer. The relevance of the genetic signature for the model is inspected by a functional analysis. RESULTS: BLASSO has been compared with a baseline LASSO model. Using 10-fold cross-validation with 100 repetitions for models' assessment, average AUC values of 0.7 and 0.69 were obtained for the Gene-specific and the Gene-disease approaches, respectively. These efficacy rates outperform the average AUC of 0.65 obtained with the LASSO. With respect to the stability of the genetic signatures found, BLASSO outperformed the baseline model in terms of the robustness index (RI). The Gene-specific approach gave RI of 0.15±0.03, compared to RI of 0.09±0.03 given by LASSO, thus being 66% times more robust. The functional analysis performed to the genetic signature obtained with the Gene-disease approach showed a significant presence of genes related with cancer, as well as one gene (IFNK) and one pseudogene (PCNAP1) which a priori had not been described to be related with cancer. CONCLUSIONS: BLASSO has been shown as a good choice both in terms of predictive efficacy and biomarker stability, when compared to other similar approaches. Further functional analyses of the genetic signatures obtained with BLASSO has not only revealed genes with important roles in cancer, but also genes that should play an unknown or collateral role in the studied disease.

Cambios ecográficos en el bulbo uretral durante la respuesta sexual femenina: un estudio piloto / Ultrasound changes in the urethral bulb during female sexual response: a pilot study

Objetivo: La submucosa del esfínter uretral interviene en el mecanismo de continencia urinaria y es rica en tejido esponjoso. La hipótesis de este estudio es que esta submucosa tiene carácter eréctil y, por tanto, debe sufrir cambios ecográficos durante la respuesta sexual en la mujer. Material y métodos: Se realiza un estudio piloto en una serie de 9 casos, mujeres sanas, con una edad media de 30,1 años y previo consentimiento informado por escrito. Para la exploración ecográfica se usa un General Electric Voluson® E8 HD. Se realiza, en primer lugar, una ecografía en estado basal, y en un segundo tiempo, en excitación sexual obtenida mediante autoestimulación. En los 4 primeros casos se realizan medidas del esfínter uretral, y en los 5 casos siguientes, además, se registra la vascularización y ecogenicidad intrauretral. Las imágenes son registradas y los datos analizados con el paquete estadístico SPSS® v. 22. Resultados: Se comprueba en la serie el aumento discreto, aunque significativo, del volumen del esfínter uretral durante la excitación sexual (p = 0,016). Además, se advirtieron importantes cambios vasculares y un cambio muy apreciable de la ecorrefringencia de la submucosa uretral, la cual pasaba de ser marcadamente hipoecogénica a ser isoecogénica. Se encontraron vasos longitudinales a lo largo de toda la submucosa en número de 3, con aferencias transversales desde el plexo de Santorini y de la pared uretrovaginal. Discusión: Con la cautela propia de un estudio piloto, se informa de cambios discretos en el volumen uretral, y cambios importantes en ecogenicidad y vascularización de la submucosa uretral durante la excitación sexual en la mujer. Estos hallazgos apoyan la hipótesis de que la submucosa uretral forma parte del sistema eréctil femenino. Se abre una nueva vía de investigación en torno a la ecografía introital como herramienta para la valoración tanto anatómica como funcional de la respuesta sexual genital femenina (AU)

Objective: The urethral sphincter submucosa is part of the urinary continence mechanism and it is rich in spongy tissue. The study hypothesis was that this submucosa has erectile properties and therefore must undergo echographic changes during the sexual response in women. Material and method: A pilot study was done in 9 healthy women with an average age of 30.1 years, after receiving prior written informed consent. For the ultrasound examination we used a General Electric Voluson® E8 HD. At the beginning we made an ultrasound in basal state and a second time during sexual arousal by self-stimulation. In the 4 former cases we measured the urethral sphincter and in the following 5 participants we also registered the vascularization and intraurethral echogenicity. Images were registered and the data were analyzed with statistical package SPSS® v. 22. Results: Discrete but significant increase in the volume of the urethral sphincter during sexual arousal (P = .016) is found in the series. In the last 5 cases of the study in addition we found important vascular changes and a significant change in echographic reference values of the urethral submucosa: it changed from markedly hypoechogenic to be isoechogenic. We found 3 longitudinal vessels along submucosa with transversal afferents from Santorini plexus and from urethrovaginal wall. Discussion: With the caution typical of a pilot study, a discrete increase of urethral volume and important changes in the urethral submucosa of echogenicity and vascularization were noticed during female sexual arousal. These results support the hypothesis that the urethral submucosa is part of the erectile female system. We offer a new way of research utilizing introital echography as a tool to evaluate anatomical and functional female genital sexual response (AU)

The efficacy of a percutaneous expandable titanium device in anatomical reduction of vertebral compression fractures of the thoracolumbar spine.

OBJECTIVES: To evaluate the feasibility of a minimally invasive technique using a titanium expandable device to achieve anatomical restoration of vertebral compression fractures (VCF) of the thoracolumbar spine. METHODS: This prospective study included 27 patients diagnosed with VCF (Magerl classification A.1.2, A.1.3, and A.3.1) of the thoracolumbar spine treated with percutaneous cement augmentation using the SpineJack® device. The study was conducted in Valladolid University Hospital, Valladolid, Spain from January to December 2012, with a minimum one-year follow up. Preoperative evaluation included visual analogue scale (VAS) for pain, and radiological assessment of the VCF using 3-dimensional computed tomography (3D-CT) scans for measurements of vertebral heights and angles. The patients were followed at 3, 6, and 12 months with clinical VAS and radiological assessments. RESULTS: The procedure was performed in 27 patients with a mean age of 55.9 ± 17.3 years, 55.6% females. All patients underwent surgery within 6 weeks from time of injury. No procedure related complications occurred. Pain measured by VAS score decreased from 7.0 preoperatively to 3.2 within 24 hours, and remained 2.2 at 3 months, 2.1 at 6 months, and 1.5 at 12-months follow-up (p<0.05). Mean height restorations for the anterior was 3.56 mm, central was 2.49, and posterior vertebral was 1.28 mm, and maintained at 12-months follow-up (p=0.001). CONCLUSION: This new percutaneous technique for VCF has shown good clinical results in pain control and the possibility to reduce both vertebral kyphosis angles and fractured endplates seen in 3D-CT scans assessment method. Further studies are needed to confirm those results on larger cohorts with long-term follow up. 

Percepción, conocimientos y actitudes de las enfermeras de urgencias y salud mental frente al alcoholismo y otras drogodependencias / Perception, knowledge and attitudes of Emergency and Mental Health nurses regarding alcoholism and other drug dependencies

OBJETIVO: describir las percepciones, conocimientos y actitudes delos profesionales de Enfermería que tratan pacientes consumidores de alcohol en las unidades de Urgencias y Salud Mental de hospitales de las Islas Baleares. MATERIAL Y MÉTODO: estudio descriptivo transversal multicéntrico sobre las enfermeras de los servicios de Urgencias y Salud Mental de cinco hospitales de las Islas Baleares. Para la recogida de los datos se utilizó la escala validada al castellano de Seaman e Mannello, que mide los conocimientos y las actitudes de los profesionales de Enfermería con relación al alcoholismo y al consumo del alcohol. RESULTADOS: se recogieron 159 cuestionarios de un universo de257. El 99,1% había tenido contacto con personas con drogodependencias durante su experiencia profesional. Cerca del 75% había tenido dificultades a la hora de atenderlos (20,6% por falta de protocolos y 17,1% por la falta de recursos). Los aspectos que dificultaban la atención eran: falta de conocimientos, actitud del propio profesional y percepción social, falta de habilidades en la comunicación, experiencias previas, organización y tipo de servicio donde trabajaba y opiniones personales. Cuando tenían dificultades, consultaban a otros profesionales para resolver sus dudas; solamente un 7,1% acudía a bases de datos científicas como fuente confiable de información. CONCLUSIONES: la enfermera percibe al paciente alcohólico como una persona enferma que necesita terapia. El déficit de conocimientos es el factor que más negativamente influye en la atención que se presta al drogodependiente, las actitudes aparecen en menor medida. El aspecto organizativo y lugar de trabajo también intervienen

OBJECTIVE: to describe the perceptions, knowledge and attitudes of nursing professionals who treat alcoholic patients in the Emergency and Mental Health units of hospitals in the Balearic Islands. MATERIALS AND METHOD: a descriptive transversal multicenter study with nurses in the Emergency and Mental Health units of five hospitals in the Balearic Islands. For data collection, the Seaman-Mannello Scale was used, validated into Spanish, which measures the knowledge and attitudes of Nursing professionals regarding alcoholism and alcohol intake. RESULTS: 150 questionnaires were collected, out of a universe of257. Out of these, 99.1% had become in contact with drug dependent persons during their professional experience. Almost 75% of them had had difficulties when managing them (20.6% due to lack of protocols, and 17.1% due to lack of resources). The factors which made patient care difficult were: lack of knowledge, attitude by the professional and social perception, lack of communication skills, previous experiences, organization and type of unit where they worked, and personal opinions. When they had difficulties, they consulted other professionals to clarify their doubts; only 7.1% used scientific databases as a reliable source of information. CONCLUSIONS: nurses perceive alcoholic patients as sick persons who need therapy. Lack of knowledge is the factor with the highest negative impact on patient care offered to drug dependent patients, while attitudes appear to a lesser extent. Organization aspects and place of work are also involved

Embarazo heterotópico diagnosticado en una cesárea a término / Gestational sack over a previous cesarean section scar: case report and review of the literature

El embarazo heterotópico está aumentando su incidencia como consecuencia del avance de las técnicas de reproducción asistida. Es importante realizar un diagnóstico precoz pues la rotura de la gestación ectópica puede llegar a ser una urgencia potencialmente mortal. Presentamos un atípico caso clínico en el que el diagnóstico de la gestación extrauterina se realizó en el transcurso de una cesárea electiva a término (AU)

We present the case of a pregnant woman with an 8-week history of amenorrhea and insertion of a gestational sac over a previous cesarean section scar. Methotrexate treatment was unsuccessful and laparotomy was performed. We provide a literature review and update on the incidence, diagnostic methods and current treatment options of this entity (AU)

Malformación arteriovenosa uterina como causa de hemorragia puerperal tardía / Uterine arteriovenous malformation as a cause of delayed postpartum hemorrhage

La malformación arteriovenosa (MAV) uterina debe incluirse en el diagnóstico diferencial de pacientes con hemorragia posparto que no cede con medidas habituales y que, incluso, empeora tras el legrado. La ecografía con Doppler color puede ayudar al diagnóstico y al manejo clínico. Aunque el tratamiento clásico ha sido la histerectomía, en la actualidad el tratamiento conservador con la embolización de la arteria uterina debería considerarse la primera opción terapéutica de estas lesiones ya que resulta seguro y efectivo. Presentamos el caso de una paciente con hemorragia puerperal tardía y MAV resuelta exitosamente con la embolización selectiva de la arteria uterina izquierda (AU)

Arteriovenous malformation (AVM) of the uterus should be included in the differential diagnosis of patients with postpartum hemorrhage that does not yield to routine measures and may even worsen after curettage. Color Doppler sonography can aid in the diagnosis and clinical management of this entity. Although the classical treatment has been hysterectomy, conservative treatment with uterine artery embolization should currently be considered the first therapeutic option for these lesions because of its safety and effectiveness. We report the case of a patient with delayed postpartum hemorrhage and AVM successfully resolved with selective embolization of the left uterine artery (AU)