Alternative Splicing and Alzheimer’s Disease

Alzheimer’s disease is a neurodegenerative process whose origin is unknown. It has been associated with this process at least two important proteins: the first is the β-amyloid forming amyloid plaques and the second protein is Tau, which has been determined to precipitates inside the neuron because hyperphosphorylation, causing instability in the axon. Tau microtubule-associated protein (MAP) is essential for the development of neuronal cell polarity. Tau protein is preferentially localized in the axons, whereas MAP2, another neuronal specific microtubule-associated protein, is localized in the somatodendritic domain. Previous studies have demonstrated that the localization of these proteins depends, at least in part, on messenger RNA (mRNA) subcellular localization, that is, Tau mRNA into the axon and MAP2 mRNA into the dendrite. Tau protein has an essential role in the pathology of Alzheimer’s disease, and hyperphosphorylated Tau promotes destabilization of microtubules. Tau alternative splicing generates six isoforms in the adult human brain due to the inclusion or exclusion of exons 2, 3, and 10. The failure in the splicing process of exon 10 generates a tauopathy, which can be carried out by the amyloid peptide; however, the splicing of other exons is less studied. The impact of amyloid peptide on the alternative splicing of exons 2, 3, and 6 caused formed cell processes to retract in differentiated cells and altered the expression of exons 2/3 in cell culture. Expression of exon 6 was repressed under β-amyloid treatment. The molecular mechanism for this amyloid-Tau interaction remains to be determined, but may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer’s disease

Oximetry use in obstructive sleep apnea

Producción CientíficaIntroduction. Overnight oximetry has been proposed as an accessible, simple, and reliable technique for obstructive sleep apnea syndrome (OSAS) diagnosis. From visual inspection to advanced signal processing, several studies have demonstrated the usefulness of oximetry as a screening tool. However, there is still controversy regarding the general application of oximetry as a single screening methodology for OSAS. Areas covered. Currently, high-resolution portable devices combined with pattern recognition-based applications are able to achieve high performance in the detection this disease. In this review, recent studies involving automated analysis of oximetry by means of advanced signal processing and machine learning algorithms are analyzed. Advantages and limitations are highlighted and novel research lines aimed at improving the screening ability of oximetry are proposed. Expert commentary. Oximetry is a cost-effective tool for OSAS screening in patients showing high pretest probability for the disease. Nevertheless, exhaustive analyses are still needed to further assess unattended oximetry monitoring as a single diagnostic test for sleep apnea, particularly in the pediatric population and in especial groups with significant comorbidities. In the following years, communication technologies and big data analysis will overcome current limitations of simplified sleep testing approaches, changing the detection and management of OSAS.This research has been partially supported by the projects DPI2017-84280-R and RTC-2015-3446-1 from Ministerio de Economía, Industria y Competitividad and European Regional Development Fund (FEDER), the project 66/2016 of the Sociedad Española de Neumología y Cirugía Torácica (SEPAR), and the project VA037U16 from the Consejería de Educación de la Junta de Castilla y León and FEDER. D. Álvarez was in receipt of a Juan de la Cierva grant IJCI-2014-22664 from the Ministerio de Economía y Competitividad

R-RAS2 overexpression in tumors of the human central nervous system

Malignant tumors of the central nervous system (CNS) are the 10th most frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of the RAS family of small GTPases. This raises the question as to whether other RAS family members may be affected in CNS tumors, excessively activating RAS pathways. The RAS-related subfamily of GTPases is that which is most closely related to classical Ras and it currently contains 3 members: RRAS, RRAS2 and RRAS3. While R-RAS and R-RAS2 are expressed ubiquitously, R-RAS3 expression is restricted to the CNS. Significantly, both wild type and mutated RRAS2 (also known as TC21) are overexpressed in human carcinomas of the oral cavity, esophagus, stomach, skin and breast, as well as in lymphomas. Hence, we analyzed the expression of R-RAS2 mRNA and protein in a wide variety of human CNS tumors and we found the R-RAS2 protein to be overexpressed in all of the 90 CNS cancer samples studied, including glioblastomas, astrocytomas and oligodendrogliomas. However, R-Ras2 was more strongly expressed in low grade (World Health Organization grades I-II) rather than high grade (grades III-IV) tumors, suggesting that R-RAS2 is overexpressed in the early stages of malignancy. Indeed, R-RAS2 overexpression was evident in pre-malignant hyperplasias, both at the mRNA and protein levels. Nevertheless, such dramatic changes in expression were not evident for the other two subfamily members, which implies that RRAS2 is the main factor triggering neural transformation.This work was supported by grants SAF2012-31279 from the ‘Comisión Interministerial de Ciencia y Tecnología’ and the ‘Ramón y Cajal’ program (RYC-2010-06251, to B.C.). We also thank the Fundación Ramón Areces for its institutional support of the ‘Centro de Biología Molecular Severo Ochoa’

Use of Botulinum Toxin in Orofacial Clinical Practice

Botulinum neurotoxin (BoNT) is a potent biological toxin and powerful therapeutic tool for a growing number of clinical orofacial applications. BoNT relaxes striated muscle by inhibiting acetylcholine’s release from presynaptic nerve terminals, blocking the neuromuscular junction. It also has an antinociceptive effect on sensory nerve endings, where BoNT and acetylcholine are transported axonally to the central nervous system. In dentistry, controlled clinical trials have demonstrated BoNT’s efficiency in pathologies such as bruxism, facial paralysis, temporomandibular joint (TMJ) disorders, neuropathic pain, sialorrhea, dystonia and more. Aim: This study’s aim was to conduct a systematic literature review to assess the most recent high-level clinical evidence for BoNT’s efficacy and for various protocols (the toxin used, dilution, dosage and infiltration sites) used in several orofacial pathologies. Materials and methods: We systematically searched the MedLine database for research papers published from 2014 to 2019 with randomly allocated studies on humans. The search included the following pathologies: bruxism, dislocation of the TMJ, orofacial dystonia, myofascial pain, salivary gland disease, orofacial spasm, facial paralysis, sialorrhea, Frey syndrome and trigeminal neuralgia. Results: We found 228 articles, of which only 20 met the inclusion criteria: bruxism (four articles), orofacial dystonia (two articles), myofascial pain (one article), salivary gland disease (one article), orofacial spasm (two articles), facial paralysis (three articles), sialorrhea (four articles) or trigeminal neuralgia (three articles). Discussion: The clinical trials assessed showed variations in the dosage, application sites and musculature treated. Thus, applying BoNT can reduce symptoms related to motor muscular activity in the studied pathologies efficiently enough to satisfy patients. We did not identify the onset of any important side effects in the literature reviewed. We conclude that treatment with BoNT seems a safe and effective treatment for the reviewed pathologie

The effects of informed consent format on preoperative anxiety in patients undergoing inferior third molar surgery

Objectives: To evaluate the effect of informed consent format on preoperative anxiety of patients. Material and Methods: We performed a prospective study (91 patients) undergoing lower third molar extraction. Patients were distributed into three groups. Informed consent for surgery was obtained through a written docu - ment, an oral interview or a video recording. Afterwards, patients were asked about their anxiety level and the effect the informed consent had had on it. Results: Whereas the information conveyed both in oral and written formats relieved the patient to some extent (in a scale of -3 to +3) 0.97±1.21 and 0.29±0.97, respectively), the video recording increased patient's anxiety in a sta - tistically significant way (in a scale of -3 to +3, -0.57±1.43). The difference obtained between the values obtained in oral and written information was not statistically significant. Discussion: The most adequate format, according to our study, would be the oral format

Sympathetic Hyperactivity and Sleep Disorders in Individuals With Type 2 Diabetes

Introduction: Many studies on the impact of type 2 diabetes mellitus (T2DM) on sleep breathing have shown a higher prevalence and severity of sleep apnea-hypopnea syndrome (SAHS) in those with T2DM. Moreover, an increased activity of the sympathetic nervous system has been described in both pathologies. This cross-sectional study aimed to assess sympathetic activity in patients with T2DM, and to investigate the relationship between sympathetic activity and polysomnographic parameters. Materials and Methods: Thirty-six patients with T2DM without known clinical macrovascularnorpulmonarydiseaseand11controlsunderwentrespiratorypolygraphy, and their cardiac variability and 24-h urine total metanephrines were measured. Results: SAHS was highly prevalent with a mean apnea-hypopnea index (AHI) in the range of moderate SAHS. In patients with T2DM, the nocturnal concentration of total metanephrines in urine were higher than diurnal levels [247.0 (120.0–1375.0) vs. 210.0 (92.0–670.0), p = 0.039]. The nocturnal total metanephrine concentration was positively and significantly associatedwith the percentage of sleeping time spent with oxygen saturation <90%(CT90). In the entire population and in subjects with T2DM, the multivariate regression analysis showed a direct interaction between the nocturnal concentration of urine metanephrines and the CT90. Conclusion: These findings suggest that the increase in sympathetic activity previously described in patients with T2DM could be mediated through nocturnal breathing disturbances. The diagnosis and treatment of SAHS may influence sympathetic activity disorders and may contribute to an improvement in T2DM and cardiovascular risk.This study was supported by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria, PI12/00803 and PI15/00260), European Union (European Regional Development Fund, Fondo Europeo de Desarrollo Regional, Una manera de hacer Europa), the Fundación Sociedad Española Endocrinología y Nutrición, and Menarini Spain S.A. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Evaluación y diseño de los procedimientos de análisis de inserción laboral de los Graduados en información y documentación. El servicio de información sobre empleo (SISE) de la Facultad de Ciencias de la Documentación (UCM)

Proyecto de innovación y mejora de Gestión de la Calidad que pretende reforzar el Sistema de Garantía Interna de Calidad de la Facultad de Ciencias de la Documentación de la UCM, y de un modo específico, el diseño de herramientas e instrumentos para la recogida de información sobre la inserción laboral de los egresados en Documentación

Influence of State Anxiety and Trate Anxiety in Postoperative in Oral Surgery

Introduction: The aim of this article was to study the influence of anxiety (both state and trait) in postoperative recovery after extraction of third molar together, to establish the role of each of the aspects of anxiety in the results you obtained in an independent and complementary way. Material and Methods: We performed a prospective study of a consecutive series of 88 patients who underwent lower third molar extractions. Before being provided with any information about the operation, patients were asked to complete the Spielberger State-Trait Anxiety Inventory-Trait and State. We have evaluated postoperative swelling and pain, patients completed a 10-point visual analog scale (VAS) at home each day (at approximately the same time of day as the operation) until day 8 after surgery, when the sutures were removed. Results: Regarding postoperative variables between positive and negative trait anxiety groups, consumption of analgesic drugs was higher in positive trait anxiety group in a statistically significant way, while these differences were detected only on specific occasions regarding pain and swelling. Discussion: In the present study, anxiety was taken into account and showed a significant effect in explaining postoperative pain and taking analgesics