Structure–activity relationships on the odor detectability of homologous carboxylic acids by humans

We measured concentration detection functions for the odor detectability of the homologs: formic, acetic, butyric, hexanoic, and octanoic acids. Subjects (14 ≤ n ≤ 18) comprised young (19–37 years), healthy, nonsmoker, and normosmic participants from both genders. Vapors were delivered by air dilution olfactometry, using a three-alternative forced-choice procedure against carbon-filtered air, and an ascending concentration approach. Delivered concentrations were established by gas chromatography (flame ionization detector) in parallel with testing. Group and individual olfactory functions were modeled by a sigmoid (logistic) equation from which two parameters are calculated: C, the odor detection threshold (ODT) and D, the steepness of the function. Thresholds declined with carbon chain length along formic, acetic, and butyric acid where they reached a minimum (ODTs = 514, 5.2, and 0.26 ppb by volume, respectively). Then, they increased for hexanoic (1.0 ppb) and octanoic (0.86 ppb) acid. Odor thresholds and interindividual differences in olfactory acuity among these young, normosmic participants were lower than traditionally thought and reported. No significant effects of gender on odor detectability were observed. The finding of an optimum molecular size for odor potency along homologs confirms a prediction made by a model of ODTs based on a solvation equation. We discuss the mechanistic implications of this model for the process of olfactory detection

ANÁLISIS DE LA SATISFACCIÓN DEL USUARIO EN CENTROS DE SALUD DEL PRIMER NIVEL DE ATENCIÓN EN LA PROVINCIA DE CÓRDOBA, ARGENTINA.

Objective: To identify users´ satisfaction about services provide for health centers in the province of Cordoba. Method: Surveys was implemented to the health centers´ users in the the province of Cordoba, asking about sociodemographic aspects, type of health care, motive of consultation, accessibility and general opinion about care received. The information collected was processed and analyzed according to the nature of the variable and comparisons were made by ANOVA and for data categorized coefficient of contingency was utilized (significance level 0.05). Results: Geographic access was considered acceptable by respondents as the waiting time and the conditions buildings. The professional performance during care, the link between the practitioner and users and the service provided by the health center were factors valued by respondents. Conclusion: The analysis of users´satisfaction of health centers is important to provide valid information for generate opportune answers and to optimize the sanitary resources.Objetivo: Identificar el nivel de satisfacción de los destinatarios de los centros de salud de la provincia de Córdoba. Método: Se implementó encuestas a los destinatarios de los centros de salud de la provincia de Córdoba indagando acerca de aspectos sociodemográficos, tipo de asistencia sanitaria, motivo de consulta, accesibilidad y opinión general de la atención recibida. La información recabada fue procesada y analizada de acuerdo a la naturaleza de la variable y las comparaciones se efectuaron por ANOVA y para datos categorizados se utilizó coeficiente de contingencia (nivel de significación 0,05). Resultados: El acceso geográfico fue considerado aceptable por los encuestados al igual que el tiempo de espera y las condiciones edilicias. El desempeño profesional durante la atención, el vínculo establecido entre el profesional y el destinatario y el servicio brindado por el centro de salud fueron factores valorizados por los encuestados. Conclusión: El análisis de la satisfacción de los destinatarios de los centros de salud es importante para proporcionar información válida para generar respuestas oportunas y optimizar los recursos sanitarios

Atención Primaria y Trastornos Mentales y de l Comportamiento: una mirada exploratoria

Objetivo: Identificar la prevalencia de los problemas de comportamiento y salud mental que se relacionan con el primer nivel de atención a partir del análisis de las estadísticas de mortalidad a nivel nacional y en la provincia de Córdoba. Metodología: La fuente analizada fue la Base de Datos de Mortalidad 2005 y 2006 del Ministerio de Salud de la Nación. Se calcularon Tasas de Mortalidad Bruta (TMB) y Específica (TME) según sexo, edad y causa por Trastornos Mentales y de Comportamiento (TMyC), Mortalidad Proporcional (MP) y la razón de tasas para país y provincia de Córdoba. Softwares SPSS e InfoStat. Resultados: En el año 2005, la TMB fue similar entre país y provincia de Córdoba, mientras que las TME por causa y por sexo fueron inferiores en Córdoba. Los TMyC representaron el 0,74% de MP en Argentina, valores similares se registraron en 2006. Entre las muertes por TMyC, los Trastornos Mentales Orgánicos (TMO) y Trastornos Mentales y del Comportamiento debido al Uso de Alcohol (TMA), ocasionaron el 96% de las muertes registradas. Las muertes por TMO se acumulan a partir de los 60 años y las muertes por TMA se expresan como causa de muerte a partir de los 30 años. Las mujeres presentan una mayor incidencia en los TMO y los varones en los TMA. En la provincia de Córdoba se observaron valores similares a los registrados en el total del país. Conclusión: La prevalencia de los TMyC observados en los registros de estadísticas vitales de Argentina y provincia de Córdoba se relacionan a patologías que están incluidas como necesidades en el primer nivel de atención

Odorant-Dependent Generation of Nitric Oxide in Mammalian Olfactory Sensory Neurons

The gaseous signalling molecule nitric oxide (NO) is involved in various physiological processes including regulation of blood pressure, immunocytotoxicity and neurotransmission. In the mammalian olfactory bulb (OB), NO plays a role in the formation of olfactory memory evoked by pheromones as well as conventional odorants. While NO generated by the neuronal isoform of NO synthase (nNOS) regulates neurogenesis in the olfactory epithelium, NO has not been implicated in olfactory signal transduction. We now show the expression and function of the endothelial isoform of NO synthase (eNOS) in mature olfactory sensory neurons (OSNs) of adult mice. Using NO-sensitive micro electrodes, we show that stimulation liberates NO from isolated wild-type OSNs, but not from OSNs of eNOS deficient mice. Integrated electrophysiological recordings (electro-olfactograms or EOGs) from the olfactory epithelium of these mice show that NO plays a significant role in modulating adaptation. Evidence for the presence of eNOS in mature mammalian OSNs and its involvement in odorant adaptation implicates NO as an important new element involved in olfactory signal transduction. As a diffusible messenger, NO could also have additional functions related to cross adaptation, regeneration, and maintenance of MOE homeostasis

PART III. ASSESSING IRRITATION: Sensory Irritation: Relation to Indoor Air Pollution

All mucosae of the body possess chemical sensitivity provided by the common chemical sense (CCS). Airborne chemicals can stimulate the CCS through the ocular, nasal, and respiratory mucosae, evoking different pungent sensations, e.g., stinging, irritation, burning, piquancy, prickling, freshness, tingling. Pungent sensations elicited in the nose differ from odor sensations in various characteristics. They are achieved at considerably higher concentrations than those necessary to elicit odor, but they increase with the concentration of the stimulus in a steeper fashion than odor. Pungent sensations from mixtures of compounds show a higher degree of addition - relative to the pungency of the individual components - than that of odor sensations. Pungency is more resistant to adaptation than odor, and, unlike it, displays considerable temporal integration with continuous stimulation. Measurement of a reflex, transitory apnea produced upon inhalation of pungent chemicals holds promise as an objective indicator of the functional status of the CCS. Results from the measurement of this reflex have agreed quantitatively with sensory data in a number of studies, showing higher common chemical sensitivity in nonsmokers - compared to smokers -, in females - compared to males -, and in young adults - compared to elderly. Research issues mentioned here include the following:      - We can rarely validate the symptoms putatively caused by indoor air pollution objectively. Without such means, we will always have the potential problem of over-reporting and embellishment. Although one person may seem more sensitive than another, the difference may lie in a greater proclivity to complain.      - Studies of anosmic persons offer a simple means to understand the functional characteristics of the nasal CCS.   Studies of chemical series in such subjects should eventually allow construction of quantitative structure-activity models for human pungency perception. The human data can be compared with relevant animal data when possible.      - The rules of additivity of pungency in mixtures need explication. Regarding the possible role of VOCs in the creation of irritation, we need to ask whether subthreshold levels add up or even amplify each other to produce noticeable irritation. Do repetitive or continuous exposures to subthreshold concentrations increase sensitivity to those substances, so that they evoke pungency when they otherwise would not? Do the various mucosae - ocular, nasal, throat - differ in their sensitivity?      - Modulation of CCS sensitivity by long-term and short-term inhalation of various agents (e.g., environmental tobacco smoke) would seem a suitable topic for further research

Comparative evaluation of seven resistance interpretation algorithms and their derived genotypic inhibitory quotients for the prediction of 48 week virological response to darunavir-based salvage regimens

Background: the darunavir genotypic inhibitory quotient (gIQ) has been suggested as one of the predictors of virological response to darunavir-containing salvage regimens. Nevertheless, which resistance algorithm should be used to optimize the calculation of gIQ is still debated. The aim of our study was to compare seven different free-access resistance algorithms and their derived gIQs as predictors of 48 week virological response to darunavir-based salvage therapy in the clinical setting. Methods: patients placed on two nucleoside reverse transcriptase inhibitors\u200a+\u200a600/100 mg of darunavir/ritonavir twice daily \u200a\ub1\u200a enfuvirtide were prospectively evaluated. Virological response was assessed at 48 weeks. Darunavir resistance interpretation was performed according to seven different algorithms, of which two were weighted algorithms. Analysis of other factors potentially associated with virological response at 48 weeks was performed. Results: fifty-six treatment-experienced patients were included. Overall, 35 patients (62.5%) had a virological response at 48 weeks. Receiver operator characteristic curve analysis showed that De Meyer's weighted score (WS) and its derived gIQ (gIQ WS) were the most accurate parameters defining virological response, and related cut-offs showed the best sensitivity/specificity pattern. In univariate logistic regression analysis, baseline log viral load (P = 0.028), optimized background score 65 2 (P = 0.048), WS >5 (P = 0.001) and WS gIQ 65 600 (P\u200a<\u200a0.0001) were independently associated with virological response. In multivariate analysis, only baseline log viral load (P = 0.008) and WS gIQ 65 600 (P < 0.0001) remained in the model. Conclusions: in our study, although different resistance interpretation algorithms and derived gIQs were associated with virological response, gIQ WS was the most accurate predictive model for achieving a successful virological response

Dissociated Representations of Pleasant and Unpleasant Olfacto-Trigeminal Mixtures: An fMRI Study

How the pleasantness of chemosensory stimuli such as odorants or intranasal trigeminal compounds is processed in the human brain has been the focus of considerable recent interest. Yet, so far, only the unimodal form of this hedonic processing has been explored, and not its bimodal form during crossmodal integration of olfactory and trigeminal stimuli. The main purpose of the present study was to investigate this question. To this end, functional magnetic resonance imaging (fMRI) was used in an experiment comparing brain activation related to a pleasant and a relatively unpleasant olfacto-trigeminal mixture, and to their individual components (CO2 alone, Orange alone, Rose alone). Results revealed first common neural activity patterns in response to both mixtures in a number of regions: notably the superior temporal gyrus and the caudate nucleus. Common activations were also observed in the insula, although the pleasant mixture activated the right insula whereas the unpleasant mixture activated the left insula. However, specific activations were observed in anterior cingulate gyrus and the ventral tegmental area only during the perception of the pleasant mixture. These findings emphasized for the firs time the involvement of the latter structures in processing of pleasantness during crossmodal integration of chemosensory stimuli