How long does tendinopathy last if left untreated? Natural history of the main tendinopathies affecting the upper and lower limb: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Natural history of disease refers to the progression of a disease process in an individual over time, in the absence of treatment. Understanding natural history of tendinopathies is key for clinicians to make accurate prognostic predictions and design effective intervention studies. OBJECTIVE: To quantify the natural history of the main tendinopathies regarding pain and function and to compare outcomes between untreated individuals and those receiving treatment. METHODS: A systematic literature search was conducted until February 2023, across PubMed, Cochrane, Embase and Scopus databases. Selection criteria included randomized controlled trials (RCTs) with a "wait-and-see" group and cohort studies with ≥3 months of follow-up reporting on pain and function-related outcomes. Standardized mean differences (SMDs) of "wait-and-see" groups were pooled using a random-effects inverse-variance model. Risk of bias was assessed using Cochrane Risk-of-Bias (RoB2), and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Six RCTs were included, encompassing 518 subjects with tendinopathy. Pooled results demonstrated significant pain (SMD = 0.30, 95%CI: 0.19-0.41) and physical function improvement (SMD = 0.38, 95%CI: 0.28-0.48). These estimates remained consistent regardless of age or follow-up duration. In rotator cuff tendinopathy, untreated individuals improved but did not fully recover at one year, with similar outcomes to other interventions (e.g., surgery). Subjects with lateral elbow, patellar and achilles tendinopathies when untreated, did not fully resolve symptoms within 12-16 weeks. CONCLUSIONS: This review provides limited conclusions about natural history of tendinopathies. Future studies should incorporate true no-intervention groups to accurately reflect tendinopathy's natural progression.

[Argentine registry of office blood pressure monitoring. RAMPAC study]. / Registro Argentino de Medición de la Presión Arterial en Consultorio. Estudio RAMPAC.

INTRODUCTION: Hypertension (HTN) is the leading cause of mortality and disability in the world. In Argentina, almost 44% of hypertensives do not know about their condition and this may be due to the low rate of blood pressure (BP) measurements during the office visit. Our hypothesis is that the measurement and electronic recording of BP (BPMR) is not a routine practice in Argentina. OBJECTIVE: To describe the rate of office BP measurement in Argentina. METHODS: This is a retrospective, multicentre, point prevalence study. We analysed all office visits on 9/19/2019 at 9 medical institutions in 6 provinces of Argentina. RESULTS: Two thousand and eighty-two office visits were analysed. The patients' mean age was 52.1 years (18-103), 1790 (59.7%) were female, and 702 (36.1%) were hypertensives. BP was measured in 420 visits (14.1%; 95% CI 12.8-15.4). In a multivariate logistic regression model, history of HTN (OR 1.91, P<.001) and previous cardiovascular event (OR 1.76, P<.001) were associated with more odds of BPMR. The presence of cancer was associated with fewer odds of BPMR (OR .51, P<.01). Cardiology measured BP up to 49.5% (144/291 visits), followed by internal medicine 30% (152/507 visits). CONCLUSION: BPMR during office visits is deficient in Argentina and represents a missed healthcare opportunity. Different strategies are needed to detect hypertensive patients and reduce cardiovascular events.

Validación externa y reproducibilidad del cuestionario PUMA para el diagnóstico de EPOC en una población latinoamericana: validación externa del cuestionario PUMA / External validation and reproducibility of the PUMA questionnaire for the diagnosis of COPD in a Latin American population: external validation of the PUMA questionnaire

Resumen El uso de escalas de predicción clínica puede incrementar la detección temprana de enfermedad pulmonar obstructiva crónica (EPOC). Su rendimiento en población latinoamericana ha sido pobremente estudiado. Nuestro objetivo fue determinar la validez y reproducibilidad del cuestionario PUMA, como herramienta de tamización en atención primaria en población colombiana, mediante un estudio tipo corte transversal; donde se establecieron las características operativas del cuestionario, área bajo la curva de características operativas del receptor (ACOR) y el mejor punto de corte para esta población. 1.980 sujetos fueron incluidos en el análisis. La prevalencia de EPOC correspondió a 18,9%. La capacidad discriminatoria del cuestionario fue de 0,69 (IC95%: 0,66-0,72), para un punto de corte óptimo mayor de 5, con una sensibilidad del 60%, especificidad 66% y un valor predictivo negativo de 88%. La escala PUMA para tamizaje de pacientes en riesgo de EPOC tiene una capacidad discriminatoria moderada y una excelente reproducibilidad en la población estudiada.

The use of clinical prediction scales may increase the early detection of chronic obstructive pulmonary disease (COPD). The performance characteristics of these scales in the Latin American population is poorly studied. We aimed to evaluate validity and reproducibility of PUMA questionnaire as a screening tool in primary care in a Colombian population. A cross-sectional study was performed. Operational characteristics of the questionnaire, the area under the received operator curve (AUROC), and the best cut-off point of the score were calculated. 1,980 individuals were included in this analysis. Prevalence of COPD was 18.9%. AUROC of the questionary was 0.69 (CI95%: 0.66-0.72), with an optimal cut-off point greater than 5 (sensitivity 60%, specificity 66%); predictive negative value was 88%. PUMA's scale for the screening of patients at risk of COPD has a moderate accuracy and an excellent reproducibility in the studied population.

[Effects of inspiratory muscle training on respiratory function and balance in stroke survivors: a randomized controlled trial]. / Efectos del entrenamiento muscular inspiratorio sobre la función respiratoria y el equilibrio en supervivientes de ictus: un ensayo clínico controlado aleatorizado.

INTRODUCTION: After a stroke, patients with hemiparesis and / or hemiplegia will present a notable asymmetry of the trunk and pelvis, and decreased postural stability and balance, affecting, consequently, respiratory function. OBJECTIVE: The objective of this study is to analyze the effects of inspiratory muscle training (IMT) on lung function, inspiratory muscle strength, postural and trunk control and balance in stroke survivors in the subacute phase. MATERIALS AND METHODS: 16 survivors of stroke in the subacute phase participated in RCT (experimental = 8; placebo = 8). The experimental group received IMT program, 5 days a week, once a day, for 8 weeks, with a progressive intensity from 15% to 60% of the PImax. The placebo group performed the same program, but with a fixed load of 7cmH20. Inspiratory muscle strength (PImax), lung function (FVC, FEV1, PEF, VMV), trunk control (TCT), and postural control and balance (PASS and Berg Scale) were evaluated. RESULTS: Experimental and placebo groups showed significant increases in PImax, with a difference between groups. There was a moderate and negative correlation between the initial PImax value and the percentage change (?PImax) (r = -0.572; p = 0.021). Significant increases in VMV (l/m) were observed in the experimental group, and increases in PASS in both groups, but without significant differences between groups. CONCLUSIONS: Inspiratory muscle training, although low intensity, is effective in improving inspiratory muscle strength in stroke survivors. However, the effects on postural control and balance remain uncertain.

TITLE: Efectos del entrenamiento muscular inspiratorio sobre la función respiratoria y el equilibrio en supervivientes de ictus: un ensayo clínico controlado aleatorizado.Introducción. Tras un ictus, los pacientes con hemiparesia y/o hemiplejía van a presentar una asimetría notable del tronco y la pelvis, y una disminución de la estabilidad postural y el equilibrio, lo que afecta, como consecuencia, a la función respiratoria. Objetivo. Analizar los efectos del entrenamiento muscular inspiratorio (EMI) sobre la función pulmonar, la fuerza muscular inspiratoria, el control postural y del tronco y el equilibrio en supervivientes de ictus. Materiales y métodos. Dieciséis pacientes supervivientes de ictus en fase subaguda participaron en un ensayo clínico controlado aleatorizado (experimental = 8; placebo = 8). El grupo experimental recibió un programa de EMI, cinco días a la semana, una vez al día, durante ocho semanas, con una intensidad progresiva del 15 al 60% de la PImáx. El grupo placebo realizó el mismo programa, pero con una carga fija de 7 cmH2O. Se evaluaron la fuerza muscular inspiratoria ­presión inspiratoria máxima (PImáx)­, la función pulmonar (capacidad vital forzada, volumen espirado en el primer segundo, flujo espiratorio máximo y ventilación voluntaria máxima), el control del tronco (test de control del tronco), y el control postural y el equilibrio ­Postural Scale for Stroke Patients (PASS) y escala de Berg­. Resultados. Los grupos experimental y placebo presentaron incrementos significativos en la PImáx, con diferencia entre grupos. Existió una correlación negativa y moderada entre el valor de la PImáx inicial y el porcentaje de cambio (?PImáx) (r = ­0,572; p = 0,021). Se observaron incrementos significativos en la ventilación voluntaria máxima (L/m) en el grupo experimental, e incrementos en la PASS en ambos grupos, pero sin diferencias significativas entre grupos. Conclusiones. El entrenamiento muscular inspiratorio, aunque de baja intensidad, es efectivo para mejorar la fuerza muscular inspiratoria en pacientes supervivientes de ictus. Sin embargo, los efectos sobre el control postural y el equilibrio permanecen inciertos.

A new graph of soil Rn-gas transport: Radon-rose plot.

Soil radon gas movement depends on soil geology, environmental thermodynamic parameters and, micro-seismic telluric activity. Mapping radon time dependent concentration at the relaxation depth in a selected area, provide transport direction in a seismically high-risk region. Nuclear track methodology is employed to determine main gradient vector for radon transport. Applying the gradient definition, a "radon rose" graph is constructed from which prone area can be promptly identified. Results show that short time interval, Rn-transport direction may change unpredictably, however, the length of each "spoke" around the circle provides information on the soil Rn-gas probable shifts towards or from a direction per time interval. The new graph is a novelty and provide improved approach for environmental protection and radon dosimetry.

Temperature and photoperiod effects on dormancy status and life cycle parameters in Aedes albopictus and Aedes aegypti from subtropical Argentina.

Aedes albopictus (Diptera: Culicidae) distribution is bounded to a subtropical area in Argentina, while Aedes aegypti (Diptera: Culicidae) covers both temperate and subtropical regions. We assessed thermal and photoperiod conditions on dormancy status, development time and mortality for these species from subtropical Argentina. Short days (8 light : 16 dark) significantly increased larval development time for both species, an effect previously linked to diapause incidence. Aedes albopictus showed higher mortality than Ae. aegypti at 16 °C under long day treatments (16 light : 8 dark), which could indicate a lower tolerance to a sudden temperature decrease during the summer season. Aedes albopictus showed a slightly higher percentage of dormant eggs from females exposed to a short day, relative to previous research in Brazilian populations. Since we employed more hours of darkness, this could suggest a relationship between day-length and dormancy intensity. Interestingly, local Ae. aegypti presented dormancy similar to Ae. albopictus, in accordance with temperate populations. The minimum dormancy in Ae. albopictus would not be sufficient to extend its bounded distribution. We believe that these findings represent a novel contribution to current knowledge about the ecophysiology of Ae. albopictus and Ae. aegypti, two species with great epidemiological relevance in this subtropical region.

Higroma quístico y la importancia de su diagnóstico prenatal: a propósito de un caso / Cystic hygroma and the importance of the prenatal diagnosis: about a case

RESUMEN El higroma quístico es la malformación del sistema linfático que más frecuentemente se observa en el período prenatal y que se ubica principalmente en el cuello y/o la nuca. Su tasa de detección ha aumentado desde la implementación de la translucencia nucal fetal (TN) en el primer trimestre de embarazo, y su presencia se ha relacionado con anomalías congénitas, aneuploidías, pérdida del embarazo y trastornos en el desarrollo. El objetivo de la presentación de este caso es resaltar la importancia del diagnóstico antenatal del higroma quístico, con el fin de realizar una intervención precoz y evitar la muerte fetal. Se recibe para estudio anatomopatológico, feto de sexo indeterminado producto del primer embarazo de una madre de 19 años de edad sin previos controles prenatales, con presencia de una gran masa quística que se extiende desde el rostro hasta la nuca. Mediante el estudio histológico se confirma el diagnóstico de higroma quístico. Al carecer de análisis de cariotipo no fue posible establecer la preexistencia de alguna anomalía genética. El también conocido como linfangioma quístico, es un tumor vascular benigno cuyo diagnóstico antenatal mediante la ultrasonografía resulta fundamental en la evolución y pronóstico de la enfermedad. Desafortunadamente en nuestro caso, la falta de controles prenatales y la ausencia de estudios ultrasonográficos que permitieran conocer las características de este linfangioma, pudo impactar significativamente en el desenlace fatal.

ABSTRACT The cystic hygroma is the malformation of the lymphatic system that is most frequently observed in the prenatal period and is located mainly in the neck and/or the nape of the neck. Its detection rate has increased since the implementation of fetal nuchal translucency (NT) in the first trimester of pregnancy and its presence has been associated with congenital abnormalities, aneuploidies, pregnancy loss, and developmental disorders. The aim of this case is to highlight the importance of antenatal diagnosis of cystic hygroma in order to perform early intervention and avoid fetal death. It is received, for anatomopathological study, a fetus of undetermined sex product of the first pregnancy of a 19 year-old mother without previous prenatal controls, with the presence of a large cystic mass that extends from the face to the neck. The histological study confirms the diagnosis of cystic hygroma. As there was no karyotype analysis, it was not possible to establish the preexistence of any genetic abnormality. Also known as cystic lymphangioma, is a benign vascular tumor whose antenatal diagnosis by ultrasonography is essential in the evolution and prognosis of the disease. Unfortunately in our case, the lack of prenatal controls and the absence of ultrasonographic studies that would allow knowing the characteristics of this lymphangioma, could significantly impact in the fatal outcome.

New target with low photoneutron yield for LINAC radiotherapy applications.

This paper presents three new materials composed of TiXV0,035XCuX-1,035 (X = 2, 4 and 6%), is proposed as Linear Accelerator target. Its response to electron beam based on photoneutron production, is assessed by MC simulation and nuclear track-etch methodology. The outcome is compared to a tungsten target irradiated by energetic 16 MeV electron beam. Photoneutron yield, of two energy groups (thermal and epithermal) were determined via converter matter 10B (98%) and Cd-filter by PADC-track density comparison. The multi-metal Ti2V0,07Cu97.93 target related to therapy beam quality, resulted advantageous in comparison to that provided by W-target, commonly used in the LINAC.

Seasonal variation of the S-index as it relates to the concentration of 222Rn inside a bunker that stores radioactive material.

In this work, the seasonal variation of the concentration of radon in soil and its contribution to concentrations inside of a bunker used for the storage and operation of radioactive material was studied. The measurements obtained inside and outside of the installation allowed establish a method for the calculation of the diffusion coefficient for the concrete, variable that directly influences the concentration of radon gas inside of the bunker. With the obtained results of the gamma dose rate and the concentration of radon inside the bunker, the S-index was calculated in order to determine whether the bunker would require some remediation process. The high radon gas concentration rates to which workers are exposed led to study the relative risk of contracting lung cancer (RRLC).

Shielding for transporting an 241Am-Be source for industrial applications.

Paraffin, water and water-extended polyester (WEP) were used as main moderator to design a mobile shielding for a 666 GBq 241Am-Be source used in oil industry. The shielding performance was estimated using Monte Carlo methods where the γ-rays induced by the neutron interaction with the shielding materials were also included. The spectra of neutrons and γ-rays around the shielding were estimated, as well as the total neutron and g-ray total fluences per history. The neutron source strength was used to calculate ambient dose equivalent rates, aiming to satisfy the international recommendation (2 mSv/h at the shielding surface). Moderators modify the neutron spectrum of the source reducing the amount of fast neutrons (0.5-11 MeV) and producing epithermal and thermal neutrons. During neutron transport in the moderator neutron capture and inelastic scattering produce gamma-rays. Paraffin has the best shielding performance however it is not suitable because can be affected by extreme temperatures. WEP and water have similar shielding performance, however water do not satisfy the international recommendations because at one site the neutron and γ-ray doses rates are larger than 2 mSv/h. WEP is the best option because fulfill the international recommendations, it is stable and temperatures where paraffin fails. The WEP-based shielding weights 66 kg.

Patients' preimplantation genetic testing decision-making experience: an opinion on related psychological frameworks.

The process of deciding whether to pursue preimplantation genetic testing (PGT) of an embryo is highly stressful for individuals and couples and has adverse emotional consequences (e.g. distress and uncertainty). PGT influences patients' lives in both positive and negative ways and is experienced at an individual level, as a dyadic unit, as a family member and as part of the society. Here, we argue that providing a conceptual framework with which to understand the `experience of decision making' about PGT for monogenic disease (PGT-M) testing specifically, as well as the factors contributing to `decisional distress' and `uncertainty' that patients endure as a result-apart from what decision they make-is crucial to optimizing patient counseling, satisfaction and outcomes in the field of ART. Derived from psychological theory, the framework proposed here identifies three categories of contributing factors to decisional distress and uncertainty in considering PGT-M; namely, 'intraindividual', 'interpersonal' and 'situational' factors. We reviewed evidence from the PGT literature to inform our framework. Well-accepted theories of stress and health decision making were also reviewed for their relevance to PGT-M decision making, focusing on potential distress and uncertainty. Our novel conceptual framework can be used to inform clinical practice, to advance research and to aid the development of interventions for individuals and couples who are deciding whether or not to use PGT-M. Alleviating emotional distress and uncertainty can improve patients' well-being during their reproductive journey.

Sexual Dysfunction and Quality of Life in Chronic Heroin-Dependent Individuals on Methadone Maintenance Treatment.

This study examined whether methadone (hereinafter referred to as MTD) maintenance treatment (MMT) is correlated with sexual dysfunction (SD) in heroin-dependent men. This was conducted to determine the prevalence of sexual dysfunction and if there is a relationship between duration and dose among men on MMT and its impact on the quality of life. The study combined a retrospective and a cross-sectional survey based on the Kinsey Scale, TECVASP, and PRSexDQ-SALSEX clinical interviews of 85 patients who are currently engaged in MMT. Sexual dysfunction in all five PRSexDQ-SALSEX domains (lack of libido, delay in orgasm, inability to orgasm, erectile dysfunction, and tolerance or acceptance of changes in sexual function) was associated with dose and long-term use of heroin. All dimensions of SD were affected by the MTD intake. From the analysis of our sample, we may conclude that dose of MTD and overall score of SD were directly associated. However, no evidence was found to prove that treatment duration and severity of SD were linked. It is notable that only one tenth of the patients spontaneously reported their symptoms of the sexual sphere, but up to a third considered leaving the MMT for this reason.

Radon concentration in hydrogeothermal deposit and spas of Boyacá, Colombia.

Inhaled radon and its progenies induce health concern due to high activity-concentration in selected thermal spas of Boyacá region. Hydrogeothermal water sources in a high risk seismic area, are studied to determine by water bubbling method radon concentration values; their occurrence is between few hundreds and 2000 Bq dm-3. Deposits, existing in this area, reach at the surface soil gas radon concentration up to 210 kBq m-3. Maintenance workers, health tourists and visitor's possible detrimental health effects, are discussed in relation to radon balneotherapy beneficial aspects.

Numerical study on electrohydrodynamic multiple droplet interactions.

We present a numerical study of inviscid multiple droplet coalescence and break-up under the action of electric forces. Using an embedded potential flow model for the droplet hydrodynamics, coupled with an unbounded exterior electrostatic problem, we are able to perform computations through various singular events and analyze the effects of the electrical field intensity on droplet interactions. Laboratory experiments on the electrodynamics of droplet pairs show a much richer, and sometimes unexpected, behavior than that of isolated droplets. For example, it has been found that opposite charged droplets tend to repel each other when the electric field intensity is above a certain critical value. Although the mathematical model employed in this work incorporates very simple flow and electric assumptions, many of the droplet coalescence patterns seen in laboratory experiments can be reproduced. In this model, the interaction pattern of two droplets of radii R_{0} separated a distance D_{0}, depends on the ratio X_{0}=D_{0}/R_{0} and the applied uniform electric field intensity, E_{∞}. By performing a vast number of numerical simulations we are able to characterize the coalescence modes before and after drop merging as a function of these two parameters. The simulations predict that droplet repulsion occurs within a narrow interval of E_{∞} values, different for each X_{0}. Surprisingly, in this E_{∞} interval, a sharp transition between two power-law precoalescence flow regimes is seen. The evolution of several flow characteristics before and after coalescence, and the shape of the deformed droplets at coalescing time and the double cone angle, are also addressed and analyzed in detail. Cone angles below 35^{∘} lead to droplet coalescence for any X_{0} value, which is in accordance with previously reported studies. Finally, it is shown that the model and algorithm can handle multiple droplet interactions. The simulations qualitatively match results from water in oil experiments in microchannels, despite the fact that the exterior fluid is not considered in the mathematical model.

Electrohydrodynamic coalescence of droplets using an embedded potential flow model.

The coalescence, and subsequent satellite formation, of two inviscid droplets is studied numerically. The initial drops are taken to be of equal and different sizes, and simulations have been carried out with and without the presence of an electrical field. The main computational challenge is the tracking of a free surface that changes topology. Coupling level set and boundary integral methods with an embedded potential flow model, we seamlessly compute through these singular events. As a consequence, the various coalescence modes that appear depending upon the relative ratio of the parent droplets can be studied. Computations of first stage pinch-off, second stage pinch-off, and complete engulfment are analyzed and compared to recent numerical studies and laboratory experiments. Specifically, we study the evolution of bridge radii and the related scaling laws, the minimum drop radii evolution from coalescence to satellite pinch-off, satellite sizes, and the upward stretching of the near cylindrical protrusion at the droplet top. Clear evidence of partial coalescence self-similarity is presented for parent droplet ratios between 1.66 and 4. This has been possible due to the fact that computational initial conditions only depend upon the mother droplet size, in contrast with laboratory experiments where the difficulty in establishing the same initial physical configuration is well known. The presence of electric forces changes the coalescence patterns, and it is possible to control the satellite droplet size by tuning the electrical field intensity. All of the numerical results are in very good agreement with recent laboratory experiments for water droplet coalescence.

Review of patient decision-making factors and attitudes regarding preimplantation genetic diagnosis.

The increasing technical complexity and evolving options for repro-genetic testing have direct implications for information processing and decision making, yet the research among patients considering preimplantation genetic diagnosis (PGD) is narrowly focused. This review synthesizes the literature regarding patient PGD decision-making factors, and illuminates gaps for future research and clinical translation. Twenty-five articles met the inclusion criteria for evaluating experiences and attitudes of patients directly involved in PGD as an intervention or considering using PGD. Thirteen reports were focused exclusively on a specific disease or condition. Five themes emerged: (1) patients motivated by prospects of a healthy, genetic-variant-free child, (2) PGD requires a commitment of time, money, energy and emotions, (3) patients concerned about logistics and ethics of discarding embryos, (4) some patients feel sense of responsibility to use available technologies, and (5) PGD decisions are complex for individuals and couples. Patient research on PGD decision-making processes has very infrequently used validated instruments, and the data collected through both quantitative and qualitative designs have been inconsistent. Future research for improving clinical counseling is needed to fill many gaps remaining in the literature regarding this decision-making process, and suggestions are offered.

Variation in xylem vulnerability to embolism in European beech from geographically marginal populations.

Climate change is expected to increase the frequency and intensity of droughts and heatwaves in Europe, leading to effects on forest growth and major forest dieback events due to hydraulic failure caused by xylem embolism. Inter-specific variability in embolism resistance has been studied in detail, but little is known about intra-specific variability, particularly in marginal populations. We evaluated 15 European beech populations, mostly from geographically marginal sites of the species distribution range, focusing particularly on populations from the dry southern margin. We found small, but significant differences in resistance to embolism between populations, with xylem pressures causing 50% loss of hydraulic conductivity ranging from -2.84 to -3.55 MPa. Significant phenotypic clines of increasing embolism resistance with increasing temperature and aridity were observed: the southernmost beech populations growing in a warmer drier climate and with lower habitat suitability have higher resistance to embolism than those from Northern Europe growing more favourable conditions. Previous studies have shown that there is little or no difference in embolism resistance between core populations, but our findings show that marginal populations have developed ways of protecting their xylem based on either evolution or plasticity.

[Regulation of the phases of the sleep-wakefulness cycle with histamine]. / Regulacion de las fases del ciclo vigilia-sueño por la histamina.

Distributed neural networks in the brain sustain generation of wakefulness and two sleep states: non-REM sleep and REM sleep. These three behavioral states are jointly ingrained in a rhythmic sequence that constitutes the sleep-wakefulness cycle. This paper reviews and updates knowledge about the involvement of the histaminergic system in sleep-wakefulness cycle organization. Histaminergic neurons are exclusively located in the hypothalamic tuberomammillary nucleus, but are the source of a widespread projection system to many brain regions. Histamine neurons are active during waking, especially with high attention need, and remain silent in both non-REM and REM sleep. There have been described four metabotropic histamine receptors, of which H1R, H2R and H3R are present in the nervous system. H1R and H2R are mainly postsynaptic heteroreceptors, whereas H3R is thought to be mostly a presynaptic auto- and hetero-receptor. Histaminergic neurons are excited by hypocretinergic neurons and most of the arousing hypocretin effects are thought to depend on histaminergic actions. Interactions among histaminergic axons and cholinergic nuclei within forebrain and brainstem are particularly important for cortical activation. In contrast, histaminergic tuberomammillary neurons, similarly to other aminergic neurons in locus coeruleus or dorsal raphe nucleus, are inhibited by non-REM sleep-promoting neurons of the preoptic region. Further inhibitory actions on histamine neurons come from adenosine release on tuberomammillary region. Finally, histaminergic neurons inhibit REM-on hypothalamic neurons containing melanine-concentrating hormone, thus supporting a permissive role of tuberomammillary nucleus in REM sleep. Actually, knockout mice for histidine decarboxylase, the enzyme synthetizing histamine, show a significant REM sleep increase.

TITLE: Regulacion de las fases del ciclo vigilia-sueño por la histamina.Redes neurales distribuidas en el encefalo sustentan la generacion de la vigilia y dos estados de sueño: sueño no REM y sueño REM. Estos tres estados comportamentales se engranan conjuntamente en una secuencia regular que constituye el ciclo vigilia-sueño. Este trabajo revisa y actualiza el conocimiento sobre la implicacion del sistema histaminergico en la organizacion del ciclo vigilia-sueño. Las neuronas histaminergicas se localizan exclusivamente en el nucleo tuberomamilar hipotalamico, pero son el origen de proyecciones extensas a numerosas regiones encefalicas. Las neuronas histaminergicas estan activas durante la vigilia, especialmente con alta demanda atencional, y permanecen silentes en sueño no REM y sueño REM. Se han descrito cuatro receptores histaminergicos metabotropicos, de los cuales H1R, H2R y H3R estan presentes en el sistema nervioso. H1R y H2R son fundamentalmente heterorreceptores postsinapticos, mientras que se piensa que H3R es mayormente un auto y heterorreceptor presinaptico. Las neuronas histaminergicas son activadas por las neuronas hipocretinergicas y se cree que muchos de los efectos activadores de las hipocretinas se deben a acciones histaminergicas. Las interacciones entre los axones histaminergicos y los nucleos colinergicos en el prosencefalo y el troncoencefalo son particularmente importantes para la activacion cortical. Por el contrario, las neuronas histaminergicas tuberomamilares, al igual que otras neuronas aminergicas del locus coeruleus o del nucleo dorsal del rafe, son inhibidas por las neuronas del area preoptica promotoras de sueño no REM. Acciones inhibidoras adicionales sobre las neuronas histaminergicas proceden de la liberacion de adenosina en la region tuberomamilar. Finalmente, las neuronas histaminergicas inhiben a las neuronas hipotalamicas REM-on que contienen hormona concentradora de melanina, apoyando asi un papel permisivo del nucleo tuberomamilar en el sueño REM. De hecho, ratones deficientes para descarboxilasa de histidina, la enzima de sintesis de la histamina, muestran un aumento significativo de sueño REM.