Changes in pharyngeal anatomy and apnea/hypopnea index after a mandibular advancement device

Objectives: This study aimed to evaluate the therapeutic effcacy of custom-made mandibular advancement devices (MAD) in the control of primary snoring and sleep apnea and to correlate with anatomical changes identified through imaging tests. Methods: Patients (n = 17) diagnosed with sleep apnea or primary snoring were included in this study and subsequently treated with MADs. Changes were assessed using a polysomnographic study (PSG), the Epworth Sleepiness Scale (ESS), and an imaging study with computed tomography scanning (CT). Studies were performed before and after the use of MAD. Anteroposterior measurements were taken in the sagittal plane at the hard palate, glottis, and supraglottic levels along the hard palate axis. Afterward, measurements were taken in the axial plane at the same levels along the hard palate axis. Results: From the six recorded measurements, the airway caliber increased by five. However, these changes were significant only in two measurements (sagittal hard palate and axial supraglottic). Snoring was controlled in 16 of the 17 subjects. From these sixteen, 12 subjects had a correct opening of the airway at the hard palate level. Moreover, daytime sleepiness decreased in all subjects. Discussion: Present results suggest that sagittal hard palate and axial supraglottic opening after use of MAD are mainly responsible for eliminating snoring and improve sleep apnea

Cognitive behavioral therapy for insomnia helps to reverse cognitive impairment in insomnia patients

Introduction: Insomnia is the most common of sleep disorders, it induces a wide variety of organic symptoms, including somatic and cognitive impairments. There are pharmacological drugs nowadays that help diminish sleep impairments due to insomnia. However, most of them seem to be worsening cognitive impairments, benzodiazepine receptor agonists, in particular, seem to induce an even worst deterioration of cognitive function. On the other hand, cognitive behavioral therapy for insomnia (CBT-I) has shown to be a reliable tool to improve the whole picture of insomnia. Objectives: To analyze the effect of CBT-I on insomnia symptoms and cognitive performance in patients suffering from chronic insomnia. Material and Methods: Ten subjects with a diagnosis of insomnia and no pharmacological treatment were evaluated pre- and post-six biweekly sessions of CBT-I with two neuropsychological batteries, BANFE and NEUROPSI attention and memory. Results: CBT-I significantly improves both the symptoms of insomnia, measured subjectively with a sleep diary and the Athens insomnia scale, and the cognitive performance measured with the neuropsychological batteries. Discussion: CBT-I is not only an effective tool for the treatment of insomnia but also helps to ameliorate cognitive performance

Las hormonas sexuales influyen en el efecto protector de la autoinmunidad mediado por linfocitos T que sobre-expresan Bcl-2

Trabajo presentado al XXXIV Congreso Nacional de la Sociedad Española de Inmunología celebrado en Palma de Mallorca del 21 al 24 de Mayo de 2008.Recientemente nuestro grupo ha demostrado que la sobre-expresión de Bcl-2 humano en linfocitos T (hBcl-2-T) de ratones transgénicos (Tg), protege contra el desarrollo de autoinmunidad. Este efecto protector esta mediado por linfocitos T reguladores CD4+CD25+. Dada la relación existente entre el desarrollo de autoinmunidad y el sexo, estudiamos la influencia de las hormonas sexuales sobre la capacidad moduladora de Bcl-2 en el desarrollo de artritis autoinmune inducida tras inmunización con colágeno bovino de tipo II (AIC). Para ello, se comparó en primer lugar el desarrollo de AIC entre ratones (DBA/1 x C57BL/6)F1-hBcl-2-T Tg y no-Tg machos y hembras. Tal y como ya se ha descrito anteriormente, los machos (DBA/1 x C57BL/6)F1 no-Tg desarrollan una AIC más acelerada e intensa que las hembras y los animales (DBA/1 x C57BL/6)F1-hBcl-2-T Tg hembras están protegidos contra el desarrollo de la enfermedad. Sin embargo, los ratones (DBA/1 x C57BL/6)F1-hBcl-2-T Tg machos desarrollan una AIC similar a la observada en las hembras F1 no-Tg. En segundo lugar, se observó que la castración de los machos F1 Tg inhibe el desarrollo de AIC y que la administración de 5¿-dihidrotestosterona a ratones (DBA/1 x C57BL/6)F1-hBcl-2-T Tg hembras bloquea el efecto protector observado en los controles no tratados. En conclusión, nuestros resultados muestran que las hormonas sexuales condicionan la capacidad de Bcl-2 para modular la actividad de los linfocitos CD4+CD25+ reguladores y el desarrollo de AIC.Peer Reviewe

Aproximación al uso de hongos entomopatógenos y vacunas para el control sostenible de garrapatas en sistemas ganaderos: revisión

La resistencia desarrollada por las garrapatas frente a los acaricidas de síntesis, hace necesario replantear las estrategias utilizadas actualmen - te para su control. Los programas de manejo integrado de parásitos se presentan como una alternativa que, al promover estrategias de con - trol basadas en la ecología y la epidemiología de cada especie de parásito, reducen el riesgo de desarrollo de resistencia. Dichas estrategias incluyen la aplicación de vacunas antigarrapata y hongos entomopatógenos que afectan la viabi - lidad y la reproducción en las garrapatas. Sin embargo, la información obtenida entre estudios sobre hongos y vacunas ha sido inconsistente, por lo que hoy en día ambas representan áreas de investigación bastante activas. El propósito de este trabajo consistió en realizar una revisión descriptiva sobre los mecanismos de acción de la vacuna antigarrapata y los hongos entomopatógenos, en la búsqueda de una po - sible complementariedad que permita el diseño de planes de aplicación conjunta, con miras a mejorar los resultados de control en sistemas ganaderos. En la primera parte del documento se revisa la actual problemática asociada al uso y abuso de los acaricidas de síntesis, haciendo un énfasis particular en el tema de resistencia; posteriormente, se describen los mecanismos de acción de hongos y vacunas que afectan la re - producción y supervivencia en garrapatas, y se incluye información relevante sobre su eficacia. Se espera que la información aquí recolectada, sirva como base para elaborar estudios que permitan identificar la utilidad de los hongos entomopatógenos y las vacunas antigarrapata al interior de los programas de manejo integrado de parásitos en ganadería

The chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors

ABSTRACT Besides the well-characterized protein network involved in the replication stress response, several regulatory RNAs have been shown to play a role in this critical process. However, it has remained elusive whether they act locally at the stressed forks. Here, by investigating the RNAs localizing on chromatin upon replication stress induced by hydroxyurea, we identified a set of lncRNAs upregulated in S-phase and controlled by stress transcription factors. Among them, we demonstrate that the previously uncharacterized lncRNA lncREST (long non-coding RNA REplication STress) is transcriptionally controlled by p53 and localizes at stressed replication forks. LncREST-depleted cells experience sustained replication fork progression and accumulate un-signaled DNA damage. Under replication stress, lncREST interacts with the protein NCL and assists in engaging its interaction with RPA. The loss of lncREST is associated with a reduced NCL-RPA interaction and decreased RPA on chromatin, leading to defective replication stress signaling and accumulation of mitotic defects, resulting in apoptosis and a reduction in tumorigenic potential of cancer cells. These findings uncover the function of a lncRNA in favoring the recruitment of replication proteins to sites of DNA replication

SNHG15 is a bifunctional MYC-regulated noncoding locus encoding a lncRNA that promotes cell proliferation, invasion and drug resistance in colorectal cancer by interacting with AIF

Abstract Background Thousands of long noncoding RNAs (lncRNAs) are aberrantly expressed in various types of cancers, however our understanding of their role in the disease is still very limited. Methods We applied RNAseq analysis from patient-derived data with validation in independent cohort of patients. We followed these studies with gene regulation analysis as well as experimental dissection of the role of the identified lncRNA by multiple in vitro and in vivo methods. Results We analyzed RNA-seq data from tumors of 456 CRC patients compared to normal samples, and identified SNHG15 as a potentially oncogenic lncRNA that encodes a snoRNA in one of its introns. The processed SNHG15 is overexpressed in CRC tumors and its expression is highly correlated with poor survival of patients. Interestingly, SNHG15 is more highly expressed in tumors with high levels of MYC expression, while MYC protein binds to two E-box motifs on SNHG15 sequence, indicating that SNHG15 transcription is directly regulated by the oncogene MYC. The depletion of SNHG15 by siRNA or CRISPR-Cas9 inhibits cell proliferation and invasion, decreases colony formation as well as the tumorigenic capacity of CRC cells, whereas its overexpression leads to opposite effects. Gene expression analysis performed upon SNHG15 inhibition showed changes in multiple relevant genes implicated in cancer progression, including MYC, NRAS, BAG3 or ERBB3. Several of these genes are functionally related to AIF, a protein that we found to specifically interact with SNHG15, suggesting that the SNHG15 acts, at least in part, by regulating the activity of AIF. Interestingly, ROS levels, which are directly regulated by AIF, show a significant reduction in SNHG15-depleted cells. Moreover, knockdown of SNHG15 increases the sensitiveness of the cells to 5-FU, while its overexpression renders them more resistant to the chemotherapeutic drug. Conclusion Altogether, these results describe an important role of SNHG15 in promoting colon cancer and mediating drug resistance, suggesting its potential as prognostic marker and target for RNA-based therapies

The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element

Abstract Background It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset of them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, and some of them have been linked to cell transformation. However, the underlying mechanisms remain poorly understood and it is unknown how the sequences of lncRNA dictate their function. Results Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in LINC-PINT that is essential for its function. This sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1. Conclusions Our findings support a conserved functional co-dependence between LINC-PINT and PRC2 and lead us to propose a new mechanism where the lncRNA regulates the availability of free PRC2 at the proximity of co-regulated genomic loci

A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions

LncRNAs have been shown to be direct players in chromatin regulation, but little is known about their role at active genomic loci. We investigate the role of lncRNAs in gene activation by profiling the RNA interactome of SMARCB1-containing SWI/SNF complexes in proliferating and senescent conditions. The isolation of SMARCB1-associated transcripts, together with chromatin profiling, shows prevalent association to active regions where SMARCB1 differentially binds locally transcribed RNAs. We identify SWINGN, a lncRNA interacting with SMARCB1 exclusively in proliferating conditions, exerting a pro-oncogenic role in some tumor types. SWINGN is transcribed from an enhancer and modulates the activation of GAS6 oncogene as part of a topologically organized region, as well as a larger network of pro-oncogenic genes by favoring SMARCB1 binding. Our results indicate that SWINGN influences the ability of the SWI/SNF complexes to drive epigenetic activation of specific promoters, suggesting a SWI/SNF-RNA cooperation to achieve optimal transcriptional activation

A lncRNA-SWI/SNF complex crosstalk controls transcriptional activation at specific promoter regions

LncRNAs have been shown to be direct players in chromatin regulation, but little is known about their role at active genomic loci. We investigate the role of lncRNAs in gene activation by profiling the RNA interactome of SMARCB1-containing SWI/SNF complexes in proliferating and senescent conditions. The isolation of SMARCB1-associated transcripts, together with chromatin profiling, shows prevalent association to active regions where SMARCB1 differentially binds locally transcribed RNAs. We identify SWINGN, a lncRNA interacting with SMARCB1 exclusively in proliferating conditions, exerting a pro-oncogenic role in some tumor types. SWINGN is transcribed from an enhancer and modulates the activation of GAS6 oncogene as part of a topologically organized region, as well as a larger network of pro-oncogenic genes by favoring SMARCB1 binding. Our results indicate that SWINGN influences the ability of the SWI/SNF complexes to drive epigenetic activation of specific promoters, suggesting a SWI/SNF-RNA cooperation to achieve optimal transcriptional activation