The gut-brain axis mediates sugar preference.

The taste of sugar is one of the most basic sensory percepts for humans and other animals. Animals can develop a strong preference for sugar even if they lack sweet taste receptors, indicating a mechanism independent of taste1-3. Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut-brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut. Using functional imaging we monitored activity of the gut-brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. Next, we engineered mice in which synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioural preference for sugar. Moreover, we show that co-opting this circuit by chemogenetic activation can create preferences to otherwise less-preferred stimuli. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for differences in the behavioural effects of sweeteners versus sugar, and uncover an essential circuit underlying the highly appetitive effects of sugar.

A neural substrate for short-term taste memories.

Real-time decisions on what foods to select for consumption, particularly in the wild, require a sensitive sense of taste and an effective system to maintain short-term taste memories, also defined as working memory in the scale of seconds. Here, we used a behavioral memory assay, combined with recordings of neural activity, to identify the brain substrate for short-term taste memories. We demonstrate that persistent activity in taste cortex functions as an essential memory trace of a recent taste experience. Next, we manipulated the decay of this persistent activity and showed that early termination of the memory trace abolished the memory. Notably, extending the memory trace by transiently disinhibiting taste cortical activity dramatically extended the retention of a short-term taste memory. Together, our results uncover taste cortex as a neural substrate for working memory and substantiate the role of sensory cortex in memory-guided actions while imposing meaning to a sensory stimulus.

Speed and accuracy of taste identification and palatability: impact of learning, reward expectancy, and consummatory licking.

Despite decades of study, it remains a matter of controversy as to whether in rats taste identification is a rapid process that occurs in about 250-600 ms (one to three licks) or a slow process that evolves over seconds. To address this issue, we trained rats to perform a taste-cued two-response discrimination task (2-RDT). It was found that, after learning, regardless of intensity, the delivery of 10 µl of a tastant (e.g., NaCl or monopotassium glutamate, MPG) was sufficient to identify its taste with maximal accuracy within 400 ms. However, despite overtraining, rats rarely stopped licking in one lick. Thus, a one-drop lick reaction task was developed in which subjects had to rapidly stop licking after release of a stop signal (tastants including water) to obtain rewards. The faster they stopped licking, the greater the reward. Rats did not stop licking after receiving either hedonically positive or negative stop signals, and thus failed to maximize rewards even when reinforced with even larger rewards. In fact, the higher the sucrose concentration given as a stop signal, the greater the number of consummatory licks elicited. However, with a stop signal of 2 mM quinine HCl, they stopped licking in ~370 ms, a time faster than that for sucrose or water, thus showing that in this rapid period, quinine HCl evoked an unpalatable response. Indeed, only when rats licked an empty sipper tube would they usually elicit a single lick to obtain a reward (operant licking). In summary, these data indicate that within 400 ms, taste identification and palatability, must either occur simultaneously or with marked overlap.

Lateral Hypothalamic GABAergic Neurons Encode and Potentiate Sucrose's Palatability.

Sucrose is attractive to most species in the animal kingdom, not only because it induces a sweet taste sensation but also for its positive palatability (i.e., oromotor responses elicited by increasing sucrose concentrations). Although palatability is such an important sensory attribute, it is currently unknown which cell types encode and modulate sucrose's palatability. Studies in mice have shown that activation of GABAergic LHAVgat+ neurons evokes voracious eating; however, it is not known whether these neurons would be driving consumption by increasing palatability. Using optrode recordings, we measured sucrose's palatability while VGAT-ChR2 transgenic mice performed a brief access sucrose test. We found that a subpopulation of LHAVgat+ neurons encodes palatability by increasing (or decreasing) their activity as a function of the increment in licking responses evoked by sucrose concentrations. Optogenetic gain of function experiments, where mice were able to choose among available water, 3% and 18% sucrose solutions, uncovered that opto-stimulation of LHAVgat+ neurons consistently promoted higher intake of the most palatable stimulus (18% sucrose). In contrast, if they self-stimulated near the less palatable stimulus, some VGAT-ChR2 mice preferred water over 18% sucrose. Unexpectedly, activation of LHAVgat+ neurons increased quinine intake but only during water deprivation, since in sated animals, they failed to promote quinine intake or tolerate an aversive stimulus. Conversely, these neurons promoted overconsumption of sucrose when it was the nearest stimulus. Also, experiments with solid foods further confirmed that these neurons increased food interaction time with the most palatable food available. We conclude that LHAVgat+ neurons increase the drive to consume, but it is potentiated by the palatability and proximity of the tastant.

Reimplantable Microdrive for Long-Term Chronic Extracellular Recordings in Freely Moving Rats.

Extracellular recordings of electrical activity in freely moving rats are fundamental to understand brain function in health and disease. Such recordings require a small-size, lightweight device that includes movable electrodes (microdrive) to record either a new set of neurons every day or the same set of neurons over time. Ideally, microdrives should be easy to implant, allowing precise and smooth displacement of electrodes. The main caveat of most commercially available microdrives is their relatively short half-life span, in average ranging from weeks to a month. For most experiments, recording days-weeks is sufficient, but when the experiment depends on training animals for several months, it is crucial to develop new approaches. Here, we present a low-cost, reusable, and reimplantable device design as a solution to extend chronic recordings to long-term. This device is composed of a baseplate that is permanently fixed to the rodent's skull, as well as a reusable and replaceable microdrive that can be attached and detached from the baseplate, allowing its implantation and reimplantation. Reimplanting this microdrive is particularly convenient when no clear neuronal signal is present, or when the signal gradually decays across days. Our microdrive incorporates a mechanism for moving a 16 tungsten-wire bundle within a small (∼15 mm3) lightweight device (∼4 g). We present details of the design, manufacturing, and assembly processes. As a proof of concept, we show that recordings of the nucleus accumbens core (NAcc) in a freely behaving rat are stable over a month. Additionally, during a lever-press task, we found, as expected, that NAc single-unit activity was associated with rewarded lever presses. Furthermore, we also show that NAc shell (NAcSh) responses evoked by freely licking for sucrose, consistent with our previously published results, were conserved from a first implant to a second microdrive reimplant in the same rat, notably showing reimplantation is possible without overtly affecting the functional responses of the area of interest. In sum, here we present a novel microdrive design (low-cost, small size, and light weight) that can be used for long-term chronic recordings and reimplanted in freely behaving rats.

Encoding of Sucrose's Palatability in the Nucleus Accumbens Shell and Its Modulation by Exteroceptive Auditory Cues.

Although the palatability of sucrose is the primary reason for why it is over consumed, it is not well understood how it is encoded in the nucleus accumbens shell (NAcSh), a brain region involved in reward, feeding, and sensory/motor transformations. Similarly, untouched are issues regarding how an external auditory stimulus affects sucrose palatability and, in the NAcSh, the neuronal correlates of this behavior. To address these questions in behaving rats, we investigated how food-related auditory cues modulate sucrose's palatability. The goals are to determine whether NAcSh neuronal responses would track sucrose's palatability (as measured by the increase in hedonically positive oromotor responses lick rate), sucrose concentration, and how it processes auditory information. Using brief-access tests, we found that sucrose's palatability was enhanced by exteroceptive auditory cues that signal the start and the end of a reward epoch. With only the start cue the rejection of water was accelerated, and the sucrose/water ratio was enhanced, indicating greater palatability. However, the start cue also fragmented licking patterns and decreased caloric intake. In the presence of both start and stop cues, the animals fed continuously and increased their caloric intake. Analysis of the licking microstructure confirmed that auditory cues (either signaling the start alone or start/stop) enhanced sucrose's oromotor-palatability responses. Recordings of extracellular single-unit activity identified several distinct populations of NAcSh responses that tracked either the sucrose palatability responses or the sucrose concentrations by increasing or decreasing their activity. Another neural population fired synchronously with licking and exhibited an enhancement in their coherence with increasing sucrose concentrations. The population of NAcSh's Palatability-related and Lick-Inactive neurons were the most important for decoding sucrose's palatability. Only the Lick-Inactive neurons were phasically activated by both auditory cues and may play a sentinel role monitoring relevant auditory cues to increase caloric intake and sucrose's palatability. In summary, we found that auditory cues that signal the availability of sucrose modulate its palatability and caloric intake in a task dependent-manner and had neural correlates in the NAcSh. These findings show that exteroceptive cues associated with feeding may enhance positive hedonic oromotor-responses elicited by sucrose's palatability.

Osteomalacia. Diagnóstico y tratamiento / Osteomalacia. Diagnosis and treatment

Introducción: la osteomalacia se caracteriza por la falta de mineralización de la sustancia osteoide, que afecta al hueso cortical y al hueso esponjoso maduro. Es una enfermedad que se presenta en adultos y niños, aunque la causa es diferente en cada uno. Objetivo: exponer la generalidad de la osteomalacia por ser una enfermedad que produce serias afectaciones a la población que la padece, especialmente a los niños. Se enfatiza en el diagnóstico y su tratamiento. Desarrollo: a fin de resumir los elementos esenciales para establecer el diagnóstico de osteomalacia hay que plantear en primer lugar, la presencia de un trastorno de la mineralización ósea, de ahí que además de tener en cuenta las causas de la enfermedad, su curso clínico y la sintomatología. Conclusiones: una recomendación importante es no tener en cuenta la posibilidad de complicaciones en el curso de la enfermedad, como las fracturas, que, aunque sean parte del cuadro clínico, al producirse pueden ocasionar graves problemas, como el caso de las que aparecen en las costillas, que si se desplazan pueden interesar órganos vitales, de modo que en este tipo de pacientes no debe excluirse la posibilidad de emergencias o de urgencias reumatológicas tanto en los adultos como en los niños(AU)

Introduction: osteomalacia is characterized by the lack of mineralization of the osteoid substance, which affects cortical bone and mature cancellous bone. It is a disease that occurs in adults and children, although the cause is different in each. Objective: to expose the generality of osteomalacia for being a disease that causes serious affectations to the population that suffers it, especially to children. Emphasis is placed on the diagnosis and its treatment. Development: in order to summarize the essential elements to establish the diagnosis of osteomalacia, we must first consider the presence of a bone mineralization disorder, hence, in addition to taking into account the causes of the disease, its clinical course and the symptomatology. Conclusions: an important recommendation is not to take into account the possibility of complications in the course of the disease, such as fractures, which, although they are part of the clinical picture, can cause serious problems when they occur, as in the case of those that appear in the ribs, which if they move may involve vital organs, so that in this type of patients should not exclude the possibility of emergencies or rheumatological emergencies in both adults and children(AU)

Prevalencia de dientes supernumerarios en niños con labio y/o paladar fisurado / Prevalence of supernumerary teeth in children with cleft lip and/or palate

El objetivo del estudio fue conocer la prevalencia de dientes supernumerarios en niños con labio y/o paladar fisurado. Se realizó un estudio transversal, se revisaron 608 ortopantomografías de expedientes de pacientes pediátricos que acuden a las clínicas de estomatología y ortodoncia del Hospital General <

The aim of the present study was to establish the prevalence of supernumerary teeth in children afflicted with cleft lip and/ or palate. A cross-sectioned study was conducted on 608 orthopantomographies from pediatric patients who attended the stomatology and orthodontics clinics of the <

Mortalidad perinatal: Estudio colaborativo institucional hospitales del sur del Perú - 2000 / Mortality perinatal: I study institutional hospitals of the south of the Peru - 2000

La Mortalidad Perinatal da imagen del nivel de desarrollo y calidad de vida de los pueblos y permite el estado de salud del producto de la concepción durante los últimos meses de vida intrauterina y los primeros 6 días de vida extrauterina. Es la primera causa de mortalidad infantil, se requiere conocer mejor nuestra realidad para elaborar estrategias que permitan superar esta situación. Conocer la magnitud de la mortalidad perinatal en 15 Hospitales del Sur del Perú y las causas relacionads con este período; además compararlas según altitud, institución de salud y control prenatal. Estudio epidemiológico, descriptivo y colaborativo, durante el año 2000, usando el Sistema Informático Perinatal en hospitales del MINSA y el Sistema de Vigilancia Perinatal en hospitales de EsSalud. De 25,940 nacimientos, 690 fueron muertes perinatales de 1000 g. a más de peso, 367 óbitos fetales tardíos y 323 neonatales precoces. La tasa global de mortalidad perinatal fue 23.46 por mil nacimientos (Fetal tardío 13.76 y neonatal precoz 9.70, con una relación de 1.5 a 1). La necropsia neonatal se realizó en tres hospitales y sólo en uno para muertes fetales. Las causas de mortalidad neonatal precoz fueron: Dificultad respiratoria (35.9 por ciento), Infecciones (25.2 por ciento), encefalopatía hipóxico isquémica (17.6 por ciento) y malformaciones congénitas (12.8 por ciento). Las principales causas específicas fueron: enfermedad de membrana hialina (30.3 por ciento) y septicemia (24.1 por ciento). El 57.8 por ciento de las muertes neonatales ocurrieron en las primeras 48 horas de vida. Las causas de mortalidad fetal tardía fueron: otras afecciones y las mal definidas (41.3 por ciento), complicaciones de la placenta cordón umbilical o membranas (14.2 por ciento), hipoxia intrauterina y asfixia (14.2 por ciento), malformaciones congénitas (7.8 por ciento) y hemorragias (7.3 por ciento). Los hospitales con mayor mortalidad perinatal fueron: Carlos Monge de Juliaca, Santa Rosa de Puerto Maldonado, Lorena y Regional del Cusco y Nuñez Butrón de Puno, todos del Ministerio de Salud, siendo la posibilidad de morir el doble que en hospitales de EsSalud...