Flavonoids as positive allosteric modulators of α7 nicotinic receptors

The use of positive allosteric modulators (PAM) of α7 nicotinic receptors is a promising therapy for neurodegenerative, inflammatory and cognitive disorders. Flavonoids are polyphenolic compounds showing neuroprotective, anti-inflammatory and pro-cognitive actions. Besides their well-known antioxidant activity, flavonoids trigger intracellular pathways and interact with receptors, including α7. To reveal how the beneficial actions of flavonoids are linked to α7 function, we evaluated the effects of three representative flavonoids -genistein, quercetin and the neoflavonoid 5,7-dihydroxy-4-phenylcoumarin- on whole-cell and single-channel currents. All flavonoids increase the maximal currents elicited by acetylcholine with minimal effects on desensitization and do not reactivate desensitized receptors, a behaviour consistent with type I PAMs. At the single-channel level, they increase the duration of the open state and produce activation in long-duration episodes with a rank order of efficacy of genistein > quercetin ≥ neoflavonoid. By using mutant and chimeric α7 receptors, we demonstrated that flavonoids share transmembrane structural determinants with other PAMs. The α7-PAM activity of flavonoids results in decreased cell levels of reactive oxygen species. Thus, allosteric potentiation of α7 may be an additional mechanism underlying neuroprotective actions of flavonoids, which may be used as scaffolds for designing new therapeutic agents

Determinación de contenido de nicotina en el tabaco de cigarrillos nacionales

La finalidad del presente trabajo obedece a que, siendo el tabaco un producto que afecta la salud del consumidor, no se ha prestado la debida atención a la cuantificación de la nicotina en los cigarrillos que se consumen en el país. La nicotina, alcaloide derivado de la piridina, es entre los constituyentes del tabaco, una sustancia tóxica al ser humano, se consideró necesario determinar la cantidad que contienen 16 marcas de cigarrillos salvadoreños. La separación y cuantificación de la nicotina se realizó siguiendo la técnica cromatográfica de capa fina y el método espectrofotométrico en la región ultra-violeta. Los análisis experimentales se efectuaron en el laboratorio del departamento de análisis químico e Instrumental, de la Facultad de Química y Farmacia de la Universidad de El Salvador. Para complementar la información se incluyen datos históricos y botánicos del tabaco, conocimientos químicos de la nicotina y referencias de ciertas enfermedades que se desarrollan con el hábito del fumado

Medidas de protección y derecho de defensa en los procesos de violencia familiar en la Corte Superior de Justicia del Santa 2022

El presente trabajo de investigación titulado entre si: Las medidas de protección y derecho de defensa en los procesos de violencia familiar en la corte superior de justicia del Santa 2022, teniendo como propósito de investigación, la determinación de la norma jurídica, si actualmente, garantiza el derecho de las víctimas de violencia familiar a tener, una protección, eficaz esto con la aplicación de las medidas de protección, para tal efecto se aplicó el diseño de investigación no experimental de tipo transeccional descriptivo simple. la investigación pretende obtener como los resultados un plan de mejora en la ejecución de las medidas de protección para con las victimas familiar para contribuir a fortalecer su uso y vigencia en nuestra realidad

Estrategias de Marketing que contribuyan al desarrollo de las PYMES del Cantón Milagro.

En el Cantón Milagro, en los últimos años, han ingresado al mercado, competidores con mayor poder económico por ende con mejor infraestructura que les permite dar una mejor atención al cliente, lo que les ha ocasionado ventajas competitivas sobre las PYMES de ese sector, quienes ven como sus ingresos no son los esperados, por lo que se propone como objetivo fortalecer la rentabilidad de las Pymes por medio del diseño y planteamiento de estrategias competitivas que permitan el afianzamiento, crecimiento y la expansión de los pequeños y medianos negocios del Cantón Milagro. Se utilizó la investigación cualicuantitativa, utilizando la encuesta. Con base en la información recopilada se concluye que los negocios están en medio crecimiento, las estrategias que aplican no les están dando los resultados esperados además que no puedan contrarrestar la competencia local ni externa. Los microempresarios no tienen conocimiento de los beneficios que ofrece el Estado para el desarrollo de sus negocios, por ende se estarían desaprovechando esos beneficios; también se puede inferir a quienes tienen negocios del tamaño en referencia (PYMES) no han sido beneficiados por las políticas de gobierno. Manejan un sistema administrativo tradicional, no aplican estrategias innovadoras que vayan acorde con los cambios del mercadoIn Milagro, in recent years, business competitors with a high economic power, which possess a better infrastructure that allows them to provide a better customer service, have entered to the market, which has generated competitive advantages over the PYMES of this sector that are able to notice that their incomes are not the ones they expected. Thus, it is proposed as an objective, to reinforce the cost-effectiveness of the PYMES through the design and the application of competitive strategies that allow the consolidation, growth, and development of the small and medium sized businesses of the sector. It was applied a quali-quantitative research, implementing some interviews. Having as a base the data collected, it is concluded that the businesses are in the middle of a developmental process and that the strategies which are been applied are not providing them the expected results, limiting them when counteracting the local and external competence. The micro-entrepreneurs do not possess knowledge related to the benefits that are offered by the government to support the development of their business; thus, those benefits are been wasted. It also can be inferred that the people who run their own business related to the size of (PYMES) have not been benefited by the governmental politics, managing a traditional administrative system; in other words, they do not implement innovative strategies which respond to the changes in the market

Rapid Differential Diagnosis between Extrapulmonary Tuberculosis and Focal Complications of Brucellosis Using a Multiplex Real-Time PCR Assay

BACKGROUND: Arduous to differ clinically, extrapulmonary tuberculosis and focal complications of brucellosis remain important causes of morbidity and mortality in many countries. We developed and applied a multiplex real-time PCR assay (M RT-PCR) for the simultaneous detection of Mycobacterium tuberculosis complex and Brucella spp. METHODOLOGY: Conventional microbiological techniques and M RT-PCR for M. tuberculosis complex and Brucella spp were performed on 45 clinical specimens from patients with focal complications of brucellosis or extrapulmonary tuberculosis and 26 control samples. Fragments of 207 bp and 164 bp from the conserved region of the genes coding for an immunogenic membrane protein of 31 kDa of B. abortus (BCSP31) and the intergenic region SenX3-RegX3 were used for the identification of Brucella and M. tuberculosis complex, respectively. CONCLUSIONS: The detection limit of the M RT-PCR was 2 genomes per reaction for both pathogens and the intra- and inter-assay coefficients of variation were 0.44% and 0.93% for Brucella and 0.58% and 1.12% for Mycobacterium. M RT-PCR correctly identified 42 of the 45 samples from patients with tuberculosis or brucellosis and was negative in all the controls. Thus, the overall sensitivity, specificity, PPV and NPV values of the M RT PCR assay were 93.3%, 100%, 100% and 89.7%, respectively, with an accuracy of 95.8% (95% CI, 91.1%-100%). Since M RT-PCR is highly reproducible and more rapid and sensitive than conventional microbiological tests, this technique could be a promising and practical approach for the differential diagnosis between extrapulmonary tuberculosis and focal complications of brucellosis

A database and digital signal processing framework for the perceptual analysis of voice quality

Bermúdez de Alvear RM, Corral J, Tardón LJ, Barbancho AM, Fernández Contreras E, Rando Márquez S, Martínez-Arquero AG, Barbancho I. A database and digital signal processing framework for the perceptual analysis of voice quality. Pan European Voice Conferenc: PEVOC 11 Abstract Book. Aug. 31-Sept.2, 2015.Introduction. Clinical assessment of dysphonia relies on perceptual as much as instrumental methods of analysis [1]. The perceptual auditory analysis is potentially subject to several internal and external sources of bias [2]. Furthermore acoustic analyses which have been used to objectively characterize pathological voices are likely to be affected by confusion variables such as the signal processing or the hardware and software specifications [3]. For these reasons the poor correlation between perceptual ratings and acoustic measures remains to be a controversial matter [4]. The availability of annotated databases of voice samples is therefore of main importance for clinical and research purposes. Databases to perform digital processing of the vocal signal are usually built from English speaking subjects’ sustained vowels [5]. However phonemes vary from one language to another and to the best of our knowledge there are no annotated databases with Spanish sustained vowels from healthy or dysphonic voices. This work shows our first steps to fill in this gap. For the aim of aiding clinicians and researchers in the perceptual assessment of voice quality a two-fold objective was attained. On the one hand a database of healthy and disordered Spanish voices was developed; on the other an automatic analysis scheme was accomplished on the basis of signal processing algorithms and supervised learning machine techniques. Material and methods. A preliminary annotated database was created with 119 recordings of the sustained Spanish /a/; they were perceptually labeled by three experienced experts in vocal quality analysis. It is freely available under Links in the ATIC website (www.atic.uma.es). Voice signals were recorded using a headset condenser cardioid microphone (AKG C-544 L) positioned at 5 cm from the speaker’s mouth commissure. Speakers were instructed to sustain the Spanish vowel /a/ for 4 seconds. The microphone was connected to a digital recorder Edirol R-09HR. Voice signals were digitized at 16 bits with 44100 Hz sampling rate. Afterwards the initial and last 0.5 second segments were cut and the 3 sec. mid portion was selected for acoustic analysis. Sennheiser HD219 headphones were used by judges to perceptually evaluate voice samples. To label these recordings raters used the Grade-Roughness-Breathiness (GRB) perceptual scale which is a modified version of the original Hirano’s GRBAS scale, posteriorly modified by Dejonckere et al., [6]. In order to improve intra- and inter-raters’ agreement two types of modifications were introduced in the rating procedure, i.e. the 0-3 points scale resolution was increased by adding subintervals to the standard 0-3 intervals, and judges were provided with a written protocol with explicit definitions about the subintervals boundaries. By this way judges could compensate for the potential instability that might occur in their internal representations due to the perceptual context influence [7]. Raters’ perceptual evaluations were simultaneously performed by means of connecting the Sennheiser HD219 headphones to a multi-channel headphone preamp Behringer HA4700 Powerplay Pro-XL. The Yin algorithm [8] was selected as initial front-end to identify voiced frames and extract their fundamental frequency. For the digital processing of voice signals some conventional acoustic parameters [6] were selected. To complete the analysis the Mel-Frequency Cepstral Coefficients (MFCC) were further calculated because they are based on the auditory model and they are thus closer to the auditory system response than conventional features. Results. In the perceptual evaluation excellent intra-raters agreement and very good inter-raters agreement were achieved. During the supervised machine learning stage some conventional features were found to attain unexpected low performance in the classification scheme selected. Mel Frequency Cepstral Coefficients were promising for assorting samples with normal or quasi-normal voice quality. Discussion and conclusions. Despite it is still small and unbalanced the present annotated data base of voice samples can provide a basis for the development of other databases and automatic classification tools. Other authors [9, 10, 11] also found that modeling the auditory non-linear response during signal processing can help develop objective measures that better correspond with perceptual data. However highly disordered voices classification remains to be a challenge for this set of features since they cannot be correctly assorted by either conventional variables or the auditory model based measures. Current results warrant further research in order to find out the usability of other types of voice samples and features for the automatic classification schemes. Different digital processing steps could be used to improve the classifiers performance. Additionally other types of classifiers could be taken into account in future studies. Acknowledgment. This work was funded by the Spanish Ministerio de Economía y Competitividad, Project No. TIN2013-47276-C6-2-R has been done in the Campus de Excelencia Internacional Andalucía Tech, Universidad de Málaga. References [1] Carding PN, Wilson JA, MacKenzie K, Deary IJ. Measuring voice outcomes: state of the science review. The Journal of Laryngology and Otology 2009;123,8:823-829. [2] Oates J. Auditory-perceptual evaluation of disordered voice quality: pros, cons and future directions. Folia Phoniatrica et Logopaedica 2009;61,1:49-56. [3] Maryn et al. Meta-analysis on acoustic voice quality measures. J Acoust Soc Am 2009; 126, 5: 2619-2634. [4] Vaz Freitas et al. Correlation Between Acoustic and Audio-Perceptual Measures. J Voice 2015;29,3:390.e1 [5] “Multi-Dimensional Voice Program (MDVP) Model 5105. Software Instruction Manual”, Kay PENTAX, A Division of PENTAX Medical Company, 2 Bridgewater Lane, Lincoln Park, NJ 07035-1488 USA, November 2007. [6] Dejonckere PH, Bradley P, Clemente P, Cornut G, Crevier-Buchman L, Friedrich G, Van De Heyning P, Remacle M, Woisard V. A basic protocol for functional assessment of voice pathology, especially for investigating the efficacy of (phonosurgical) treatments and evaluating new assessment techniques. Guideline elaborated by the Comm. on Phoniatrics of the European Laryngological Society (ELS). Eur Arch Otorhinolaryngol 2001;258:77–82. [7] Kreiman et al. Voice Quality Perception. J Speech Hear Res 1993;36:21-4 [8] De Cheveigné A, Kawahara H. YIN, a fundamental frequency estimator for speech and music. J. Acoust. Soc. Amer. 202; 111,4:1917. [9] Shrivastav et al. Measuring breathiness. J Acoust Soc Am 2003;114,4:2217-2224. [10] Saenz-Lechon et al. Automatic Assessment of voice quality according to the GRBAS scale. Eng Med Biol Soc Ann 2006;1:2478-2481. [11] Fredouille et al. Back-and-forth methodology for objective voice quality assessment: from/to expert knowledge to/from automatic classification of dysphonia. EURASIP J Appl Si Pr 2009.Campus de Excelencia Internacional Andalucía Tech, Universidad de Málaga. Ministerio de Economía y Competitividad, Projecto No. TIN2013-47276-C6-2-R

The Nicotinic a5 Subunit Can Replace Either an Acetylcholine-Binding or Nonbinding Subunit in the a4b2* Neuronal Nicotinic Receptor

ABSTRACT Heteropentameric neuronal nicotinic receptors assemble so that the canonical acetylcholine-binding sites are located at the interfaces between two pairs of subunits, while the fifth subunit does not participate in a canonical transmitter-binding site. Several subunits are considered to be unable to participate in forming a functional receptor when they occupy a position that would contribute to such a site, including the a5 subunit. The a5 subunit is of interest because of its apparent involvement in nicotine dependence and in the control of dopamine release. We have examined this question using a4 and b2 subunits in concatemeric constructs with the a5 subunit, expressed in Xenopus oocytes. Using dimeric constructs of a4 and b2 subunits expressed with free a5 and pentameric constructs incorporating a single copy of a5, we find that the a5 subunit can occupy the position of a nonbinding subunit, or replace a b2 subunit participating in a canonical binding site. The resulting receptors functionally resemble pentamers assembled with two copies of a4 and three copies of b2. Functional receptors apparently cannot be formed with a5 subunits in both canonical binding sites. These observations extend the present ideas on the possible positions in the pentamer that may be occupied by the a5 subunit, and suggest that additional physiologic or pharmacological subtypes of neuronal nicotinic receptors may be present in neurons

alpha 4 beta 2 Nicotinic Acetylcholine Receptors: Relationships Between Subunit Stoichiometry and Function at the Single Channel Level

Acetylcholine receptors comprising alpha 4 and beta 2 subunits are the most abundant class of nicotinic acetylcholine receptor in the brain. They contribute to cognition, reward, mood, and nociception and are implicated in a range of neurological disorders. Previous measurements of whole-cell macroscopic currents showed that alpha 4 and beta 2 subunits assemble in two predominant pentameric stoichiometries, which differ in their sensitivity to agonists, antagonists, and allosteric modulators. Here we compare agonist-elicited single channel currents from receptors assembled with an excess of either the alpha 4 or beta 2 subunit, forming receptor populations biased toward one or the other stoichiometry, with currents from receptors composed of five concatemeric subunits in which the subunit stoichiometry is predetermined. Our results associate each subunit stoichiometry with a unique single channel conductance, mean open channel lifetime, and sensitivity to the allosteric potentiator 3-[3-(3-pyridinyl)-1,2,4-oxadiazol-5-yl] benzonitrile (NS-9283). Receptors with the composition (alpha 4 beta 2)(2)alpha 4 exhibit high single channel conductance, brief mean open lifetime, and strong potentiation by NS-9283, whereas receptors with the composition (alpha 4 beta 2)(2)beta 2 exhibit low single channel conductance and long mean open lifetime and are not potentiated by NS-9283. Thus single channel current measurements reveal bases for the distinct functional and pharmacological properties endowed by different stoichiometries of alpha 4 and beta 2 subunits and establish pentameric concatemers as a means to delineate interactions between subunits that confer these properties

Factors associated with improvement in disability-adjusted life years in patients with HIV/AIDS

Background: The epidemic of HIV/AIDS and treatments that have emerged to alleviate, have brought about a shift in the burden of disease from death to quality of life/disability. The aim was to determine which factors are associated with improvements in the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years. Methods: Descriptive study based on a sample group of 8800 people on the Andalusian AIDS register between 1983 and 2004. Dependent variables: Life lost due to premature mortality (YLL), years lost due to disability (YLD) and disability-adjusted life years (DALY). Independent variables: vital state, sex, age at the time of diagnosis, age at the time of death, transmission category, province of residence, AIDS-indicator disease and the period of diagnosis. A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables. Using the independent variables which had a statistically significant link with the level of health variables, a multivariate linear regression model, disaggregated by gender, was constructed. Results: Amongst the women, we found a model which explained the level of health of 64.9%: a link was found between a higher level of health (lower DALYs) and not intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Amongst the men, we found a model which explained the level of health of 64.4%: a link was found between a higher level of health (lower DALYs) and intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Conclusion: A higher level of health (lower DALY) amongst both men and women was found to be linked to not be intravenous drug user, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis

Incidencia de los objetos virtuales de aprendizaje en el desarrollo de la competencia interpretativa en niños de básica primaria con TDA

Maestría en EducaciónThe present investigation had as a purpose to analyze the influence of the Virtual Learning Objects (VLO) in the development of the interpretative skill in primary school kids with TDA. A simple or unit of analysis of 25 students with previous TDA diagnostics. In the grades 3, 4 and 5 from the basic primary in a private institution. Likewise, the opinion of Spanish teachers was taken into consideration regarding the didactic strategies and actions utilized with these children. Fort he collection of the information, the following tolos were used: a check list and a pre-assessment to diagnose the status of the interpretative skill among the children. Then, during the process of formation, the strategy of VLO in language was implemented with the objective of developing the interpretative skill. At the end of the marking period, a post- assessment with the purpose of determining the influence that the VLO had in the development of the interpretative skill for children with TDA. Similarly, the Socrative Software was used as a tool of Access, development and storage of the results of evaluative activities. The results showed the applicability of the VLO notoriously influenced in the development of the interpretative skill, since it allowed all students to move from a low level to a médium level, as it is observed in the mode as a measure of central tendency, in the graphs of absolute frequency and in the graph of normal distribution or Gauss Bell.La presente investigación tuvo como propósito analizar la incidencia de los Objetos Virtuales de Aprendizaje (OVA) en el desarrollo de la competencia interpretativa en niños de básica primaria con TDA. Se trabajó con una unidad de análisis constituida por 25 estudiantes con diagnóstico previo de TDA de los grados 3° a 5º de básica primaria en una institución privada. De igual manera, fue considerada la opinión de los docentes de lengua castellana en cuanto a las estrategias didácticas y acciones utilizadas con estos niños. Para la recogida de información, se utilizó como instrumentos: un checklist y un pre-test para diagnosticar el estado de la competencia interpretativa de los niños, luego durante su proceso de formación se les aplicó como estrategia didáctica OVA de lenguaje a fin de desarrollar la competencia interpretativa Al finalizar el periodo lectivo, se aplicó un Postest con el fin de analizar la incidencia que el OVA había surtido en el desarrollo de la competencia interpretativa de los niños con TDA, de igual manera, se utilizó el software Socrative como herramienta de acceso, desarrollo y almacenamiento de los resultados de las actividades evaluativas. Los resultados mostraron que la aplicabilidad del OVA, incidió notablemente en el desarrollo de la competencia interpretativa, toda vez que permitió que los estudiantes pasaran de un nivel bajo a nivel medio de interpretación, observada en la moda como medida de tendencia central, en las gráficas de frecuencia absoluta y en las gráficas de distribución normal o campana de Gauss