Intracuneate mechanisms underlying primary afferent cutaneous processing in anaesthetized cats

[Abstract] The cutaneous primary afferents from the upper trunk and forelimbs reach the medial cuneate nucleus in their way towards the cerebral cortex. The aim of this work was twofold: (i) to study the mechanisms used by the primary afferents to relay cutaneous information to cuneate cuneolemniscal (CL) and noncuneolemniscal (nCL) cells, and (ii) to determine the intracuneate mechanisms leading to the elaboration of the output signal by CL cells. Extracellular recordings combined with microiontophoresis demonstrated that the primary afferent cutaneous information is communicated to CL and nCL cells through AMPA, NMDA and kainate receptors. These receptors were sequentially activated: AMPA receptors participated mainly during the initial phase of the response, whereas kainate- and NMDA-mediated activity predominated during a later phase. The involvement of NMDA receptors was confirmed by in vivo intracellular recordings. The cutaneous-evoked activation of CL cells was decreased by GABA and increased by glycine acting at a strychnine-sensitive site, indicating that glycine indirectly affects CL cells. Two subgroups of nCL cells were distinguished based on their sensitivity to iontophoretic ejection of glycine and strychnine. Overall, the results support a model whereby the primary afferent cutaneous input induces a centre-surround antagonism in the cuneate nucleus by activating (via AMPA, NMDA and kainate receptors) and disinhibiting (via serial glycinergic–GABAergic interactions) a population of CL cells with overlapped receptive fields that at the same time inhibit (via GABAergic cells) other neighbouring CL cells with different receptive fields.Ministerio de Ciencia y Tecnología; BFI 2003-0194

Moderate exercise prevents insulin resistance and changes in adrenocortical morphology and function in rats fed a sucrose-enriched diet

Introducción: niveles elevados de glucocorticoides se asocian a las alteraciones somáticas y bioquímicas presentes en los pacientes y en animales con insulinorresistencia (IR). Hemos demostrado previamente que la IR inducida por una dieta rica en sacarosa (DRS) induce cambios morfológicos y funcionales a nivel adrenocortical y que estas alteraciones pueden evitarse mediante la administración simultánea de un agonista PPAR-γ. Objetivos: en el presente estudio evaluamos el impacto de un protocolo de ejercicio moderado sobre las alteraciones morfológicas y funcionales adrenocorticales asociadas con el desarrollo de IR inducida por una DRS administrada durante siete semanas.Metodología. Resultados: los animales (ratas Wistar macho adultas) tratados con la DRS (agregado de sacarosa al 30% en el agua de bebida) mostraron un incremento del peso corporal y de los panículos adiposos, así como de los niveles séricos de glucosa, insulina y triglicéridos. La respuesta glucémica a la administración de insulina i.p. se vio claramente menoscabada. Se observó una infiltración lipídica de la corteza adrenal, con aumento de la expresión de proteínas esteroidogénicas y marcadores de inflamación (IL-1β, TNF-α, iNOS, COX-2) y un incremento marcado de la corticosteronemia basal. El protocolo de ejercicio consistió en correr en una cinta continua adaptada especialmente durante un máximo de 7 min/día. Este ejercicio moderado previno la aparición de los cambios somáticos y bioquímicos característicos del estado de IR y la infiltración lipídica adrenocortical, revirtiendo además los cambios inflamatorios y normalizando la corticosteronemia. Conclusiones: nuestros resultados subrayan el rol deletéreo del consumo exagerado de carbohidratos simples conteniendo fructosa y sugieren que el ejercicio moderado podría tener efectos adicionales cuando se emplea en el tratamiento de la IR.Introduction: a sustained elevation of glucocorticoid production has been associated with the somatic and biochemical changes observed in insulin-resistant patients and in animal models of insulin resistance (IR) as well. We previously demonstrated that sucrose-induced IR affects adrenocortical morphology and function, and that these abnormalities could be prevented by the administration of an insulin-sensitizing PPAR-γ agonist. Objetives: in this study, we analyzed the impact of moderate exercise on changes in adrenocortical function and morphology associated with the development of IR, generated in male adult rats by the addition of 30% sucrose to the drinking water for 7 weeks. Methodology. Results: body and adipose tissue weights increased in sucrose-treated animals, who also displayed higher glycemic and insulinemic levels as well as hypertriglyceridemia. An altered glycemic response to an i.p. insulin test was also detected. Adrenal glands showed a neutral lipid infiltration and increased expression levels of StAR, CYP11A1, IL-1β, TNF-α, iNOS and COX-2. Furthermore, sucrose-treated animals exhibited higher basal corticosterone levels. Exercise training sessions consisted of running on an adapted motorized treadmill for up to 7 min/day. This moderate exercise protocol fully prevented the instauration of the IR-associated somatic and metabolic changes as well as the lipidic infiltration of the adrenal glands, and reversed the inflammatory changes and the increase in corticosterone output. Conclusions: our results underline the negative impact of high dietary fructose consumption, and suggest that moderate exercise could exert additional beneficial effects when employed as a therapeutic strategy in the management of IR.Fil: Martinez Calejman, Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Mercau, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Repetto, Esteban Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Astort, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Arias, Pablo. Universidad Nacional de Rosario. Facultad de Cs.médicas. Escuela de Cs.médicas. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Significado que le atribuyen al compromiso organizacional los docentes del nivel secundario de la institución educativa José Carlos Mariátegui del distrito el Porvenir, 2020

El propósito del presente estudio fue comprender el significado que le atribuyen al compromiso organizacional los docentes del nivel secundario de la Institución Educativa José Carlos Mariátegui del distrito El Porvenir 2020. La metodología del estudio, se centró en el enfoque cualitativo, en el nivel descriptivo, con un diseño fenomenológico. La muestra de estudio estuvo conformada por 10 docentes del nivel secundario con más de cinco años de antigüedad en la institución. La técnica para el recojo de información, fue la entrevista a profundidad, en donde el instrumento utilizado fue la guía de entrevista. Los hallazgos reflejaron que, el significado que le atribuyeron al compromiso organizacional afectivo los docentes, es que, con el paso del tiempo se ha generado vínculos de apego y sentido de pertenencia con su institución, en donde se sienten orgullosos de pertenecer a esta gran familia, generando un compromiso de contribuir al engrandecimiento de la institución. Es importante señalar que mientras más es el tiempo de permanencia en la institución, mayor es el vínculo afectivo y el grado de identificación con la institución que les brindó la oportunidad de desarrollarse y crecer profesionalmente. En conclusión, el significado que le atribuyeron al compromiso organizacional los docentes, es que, se identifican con la filosofía de servicio de la institución y su misión y visión compartida, generando el cumplimiento de sus responsabilidades y la práctica de los valores y principios institucionales, favoreciendo en un clima armonioso entre todos sus miembros y al engrandecimiento institucional.Tesi

Effects of GABA B receptor agonists and antagonists on glycemia regulation in mice

γ-Aminobutyric acid (GABA) inhibits insulin secretion through GABAB receptors in pancreatic β-cells. We investigated whether GABAB receptors participated in the regulation of glucose homeostasis in vivo. BALB/c mice acutely pre-injected with the GABAB receptor agonist baclofen (7.5 mg/kg, i.p.) presented glucose intolerance and diminished insulin secretion during a glucose tolerance test (GTT, 2 g/kg body weight, i.p.). The GABAB receptor antagonist 2-hydroxysaclofen (15 mg/kg, i.p.) improved the GTT and reversed the baclofen effect. Also a slight increase in insulin secretion was observed with 2-hydroxysaclofen. In incubated islets 1.10−5 M baclofen inhibited 20 mM glucose-induced insulin secretion and this effect was reversed by coincubation with 1.10−5 M 2-hydroxysaclofen. In chronically-treated animals (18 days) both the receptor agonist (5 mg/kg/day i.p.) and the receptor antagonist (10 mg/kg/day i.p.) induced impaired GTTs; the receptor antagonist, but not the agonist, also induced a decrease in insulin secretion. No alterations in insulin tolerance tests, body weight and food intake were observed with the treatments. In addition glucagon, insulin-like growth factor I, prolactin, corticosterone and growth hormone, other hormones involved in glucose metabolism regulation, were not affected by chronic baclofen or 2-hydroxysaclofen. In islets obtained from chronically injected animals with baclofen, 2-hydroxysaclofen or saline (as above), GABAB2 mRNA expression was not altered. Results demonstrate that GABAB receptors are involved in the regulation of glucose homeostasis in vivo. Treatment with receptor agonists or antagonists, given acutely or chronically, altered glucose homeostasis and insulin secretion alerting to the need to evaluate glucose metabolism during the clinical use of these drugs.Fil: Bonaventura, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Crivello, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Ferreira, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Repetto, Martín. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Cymeryng, Cora Betriz. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Libertun, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lux Lantos, Victoria A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Melatonin prevents early pituitary dysfunction induced by sucrose-rich diets

While physiological levels of glucocorticoids are required to ensure proper functions of the body, consistently high levels may engender several deleterious consequences. We have previously shown an increase in the activity of the hypothalamic-pituitary-adrenal (HPA) axis in rats fed sucrose-rich diets (SRD). The main goal of this study was to analyze the processes involved in the modulation of the pituitary production of ACTH by SRD, and to test melatonin as a possible therapeutic agent for the prevention of the HPA axis dysfunction. Male Wistar rats were fed standard chow and either SRD (30% sucrose in the drinking water) or plain water for three weeks. Melatonin was administered as subcutaneous pellets. Results showed that SRD treatment induced an increase in systemic ACTH and corticosterone levels and a decrease in melatonin levels. In the pituitary gland, we also detected an increase in the expression levels of proopiomelanocortin (POMC) that was accompanied by increased levels of: lipoperoxides, nitro-tyrosine modified proteins, catalase, heme oxygenase-1, interleukin-1β mRNA, and by an increase in the tissue number of inflammatory cells (F4/80 and Iba-1 positive cells). Melatonin treatment prevented all these systemic and pituitary changes as well as the increase in POMC expression induced by incubation of AtT-20 corticotrophs with conditioned media obtained from stimulated macrophages. In conclusion, stimulation of POMC/ACTH production in rats fed a SRD could involve the generation of oxidative stress and inflammation in the pituitary gland. Melatonin treatment prevented these effects and normalized the activity of the HPA axis.Fil: Mercau, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Calanni, Juan Salvador. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Aranda, Marcos Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Caldareri, Lilian Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Rosenstein, Ruth Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Repetto, Esteban Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; ArgentinaFil: Cymeryng, Cora Betriz. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentin

Backsplash galaxies and their impact on galaxy evolution: a three-stage, four-type perspective

We study the population of backsplash galaxies at $z=0$ in the outskirts of massive, isolated clusters of galaxies taken from the MDPL2-SAG semi-analytic catalogue. We consider four types of backsplash galaxies according to whether they are forming stars or passive at three stagesin their lifetimes: before entering the cluster, during their first incursion through the cluster, and after they exit the cluster. We analyse several geometric, dynamic, and astrophysical aspects of the four types at the three stages. Galaxies that form stars at all stages account for the majority of the backsplash population ($58\%$) and have stellar masses typically below $M_\star\sim 3\times 10^{10} h^{-1}{\rm M}_\odot$ that avoid the innermost cluster's regions and are only mildly affected by it. In a similar mass range, galaxies that become passive after exiting the cluster ($26\%$) follow orbits characterised by small pericentric distance and a strong deflection by the cluster potential well while suffering a strong loss of both dark matter and gas content. Only a small fraction of our sample ($4\%$) become passive while orbiting inside the cluster. These galaxies have experienced heavy pre-processing and the cluster's tidal stripping and ram pressure provide the final blow to their star formation. Finally, galaxies that are passive before entering the cluster for the first time ($12\%$) are typically massive and are not affected significantly by the cluster. Using the bulge/total mass ratio as a proxy for morphology, we find that a single incursion through a cluster do not result in significant morphological changes in all four types.Comment: Accepted for publication in MNRAS. Comments are welcom

ROGER: Reconstructing orbits of galaxies in extreme regions using machine learning techniques

We present the ROGER (Reconstructing Orbits of Galaxies in Extreme Regions) code, which uses three different machine learning techniques to classify galaxies in, and around, clusters, according to their projected phase-space position. We use a sample of 34 massive, M200 > 1015h-1M⊙, galaxy clusters in the MultiDark Planck 2 (MDLP2) simulation at redshift zero. We select all galaxies with stellar mass M∗ ≥ 108.5h-1M⊙, as computed by the semi-analytic model of galaxy formation SAG, that are located in, and in the vicinity of, these clusters and classify them according to their orbits. We train ROGER to retrieve the original classification of the galaxies from their projected phase-space positions. For each galaxy, ROGER gives as output the probability of being a cluster galaxy, a galaxy that has recently fallen into a cluster, a backsplash galaxy, an infalling galaxy, or an interloper. We discuss the performance of the machine learning methods and potential uses of our code. Among the different methods explored, we find the K-Nearest Neighbours algorithm achieves the best performance.Fil: de Los Rios, Martín Emilio. South American Institute For Fundamental Research.; BrasilFil: Martínez, Héctor J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Coenda, Valeria. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Muriel, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Ruiz, Andrés Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Vega Martínez, Cristian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Cora, Sofia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; Argentin

Reconstructing orbits of galaxies in extreme regions (ROGER) - II: Reliability of projected phase-space in our understanding of galaxy populations

We connect galaxy properties with their orbital classification by analysing a sample of galaxies with stellar mass M⋆ ≥ 108.5h-1M⊙ residing in and around massive and isolated galaxy clusters with mass M200 > 1015h-1M⊙ at redshift z = 0. The galaxy population is generated by applying the semi-analytic model of galaxy formation sag on the cosmological simulation MultiDark Planck 2. We classify galaxies considering their real orbits (3D) and their projected phase-space position using the roger code (2D). We define five categories: cluster galaxies, galaxies that have recently fallen into a cluster, backsplash galaxies, infalling galaxies, and interloper galaxies. For each class, we analyse the 0.1(g - r) colour, the specific star formation rate (sSFR), and the stellar age, as a function of the stellar mass. For the 3D classes, we find that cluster galaxies have the lowest sSFR, and are the reddest and the oldest, as expected from environmental effects. Backsplash galaxies have properties intermediate between the cluster and recent infaller galaxies. For each 2D class, we find an important contamination by other classes. We find it necessary to separate the galaxy populations in red and blue to perform a more realistic analysis of the 2D data. For the red population, the 2D results are in good agreement with the 3D predictions. Nevertheless, when the blue population is considered, the 2D analysis only provides reliable results for recent infallers, infalling galaxies and interloper galaxies.Fil: Coenda, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; ArgentinaFil: de Los Rios, Martín Emilio. Universidad Autónoma de Madrid; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Muriel, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; ArgentinaFil: Cora, Sofia Alejandra. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Martinez, Hector Jose Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; ArgentinaFil: Ruiz, Andrés Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; Argentina. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; ArgentinaFil: Vega Martínez, Cristian Antonio. Universidad de La Serena; Chile. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; Argentin

The cold-sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature

[Abstract] Aim: Physiological functions in mammals show circadian oscillations, synchronized by daily cycles of light and temperature. Central and peripheral clocks participate in this regulation. Since the ion channel TRPM8 is a critical cold sensor, we investigated its role in circadian function. Methods: We used TRPM8 reporter mouse lines and TRPM8-deficient mice. mRNA levels were determined by in situ hybridization or RT-qPCR and protein levels by immunofluorescence. A telemetry system was used to measure core body temperature (Tc). Results: TRPM8 is expressed in the retina, specifically in cholinergic amacrine interneurons and in a subset of melanopsin-positive ganglion cells which project to the central pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. TRPM8-positive fibres were also found innervating choroid and ciliary body vasculature, with a putative function in intraocular temperature, as shown in TRPM8-deficient mice. Interestingly, Trpm8-/- animals displayed increased expression of the clock gene Per2 and vasopressin (AVP) in the SCN, suggesting a regulatory role of TRPM8 on the central oscillator. Since SCN AVP neurons control body temperature, we studied Tc in driven and free-running conditions. TRPM8-deficiency increased the amplitude of Tc oscillations and, under dim constant light, induced a greater phase delay and instability of Tc rhythmicity. Finally, TRPM8-positive fibres innervate peripheral organs, like liver and white adipose tissue. Notably, Trpm8-/- mice displayed a dysregulated expression of Per2 mRNA in these metabolic tissues. Conclusion: Our findings support a function of TRPM8 as a temperature sensor involved in the regulation of central and peripheral clocks and the circadian control of Tc.Ministerio de Ciencia e Innovación (España); RT2018-099995-B100Ministerio de Ciencia e Innovación (España); AEI/10.13039/501100011033Generalitat Valenciana; PROMETEO/2021/031Ministerio de Asuntos Económicos y Transformación Digital (España); BES-2011-04706

Identifying the needs of older people living with HIV (≥ 50 years old) from multiple centres over the world: a descriptive analysis

BackgroundOlder People Living with HIV (OPWH) combine both aging and HIV-infection features, resulting in ageism, stigma, social isolation, and low quality of life. This context brings up new challenges for healthcare professionals, who now must aid patients with a significant comorbidity burden and polypharmacy treatments. OPWH opinion on their health management is hardly ever considered as a variable to study, though it would help to understand their needs on dissimilar settings.MethodsWe performed a cross-sectional, comparative study including patients living with HIV aged >= 50 years old from multiple centers worldwide and gave them a survey addressing their perception on overall health issues, psychological problems, social activities, geriatric conditions, and opinions on healthcare. Data was analyzed through Chisquared tests sorting by geographical regions, age groups, or both.ResultsWe organized 680 participants data by location (Center and South America [CSA], Western Europe [WE], Africa, Eastern Europe and Israel [EEI]) and by age groups (50- 55, 56-65, 66-75, >75). In EEI, HIV serostatus socializing and reaching undetectable viral load were the main problems. CSA participants are the least satisfied regarding their healthcare, and a great part of them are not retired. Africans show the best health perception, have financial problems, and fancy their HIV doctors. WE is the most developed region studied and their participants report the best scores. Moreover, older age groups tend to live alone, have a lower perception of psychological problems, and reduced social life.ConclusionsPatients' opinions outline region- and age-specific unmet needs. In EEI, socializing HIV and reaching undetectable viral load were the main concerns. CSA low satisfaction outcomes might reflect high expectations or profound inequities in the region. African participants results mirror a system where general health is hard to achieve, but HIV clinics are much more appealing to them. WE is the most satisfied region about their healthcare. In this context, age-specific information, education and counseling programs (i.e. Patient Reported Outcomes, Patient Centered Care, multidisciplinary teams) are needed to promote physical and mental health among older adults living with HIV/AIDS. This is crucial for improving health-related quality of life and patient's satisfaction