Microglial repopulation alleviates age-related decline of stable wakefulness in mice.

Changes in wake/sleep architecture have been observed in both aged human and animal models, presumably due to various functional decay throughout the aging body particularly in the brain. Microglia have emerged as a modulator for wake/sleep architecture in the adult brain, and displayed distinct morphology and activity in the aging brain. However, the link between microglia and age-related wake/sleep changes remains elusive. In this study, we systematically examined the brain vigilance and microglia morphology in aging mice (3, 6, 12, and 18 months old), and determined how microglia affect the aging-related wake/sleep alterations in mice. We found that from young adult to aged mice there was a clear decline in stable wakefulness at nighttime, and a decrease of microglial processes length in various brain regions involved in wake/sleep regulation. The decreased stable wakefulness can be restored following the time course of microglia depletion and repopulation in the adult brain. Microglia repopulation in the aging brain restored age-related decline in stable wakefulness. Taken together, our findings suggest a link between aged microglia and deteriorated stable wakefulness in aged brains.

Influence of Effort-based Reward Training on Neuroadaptive Cognitive Responses: Implications for Preclinical Behavioral Approaches for Depressive Symptoms.

Despite the presence of multiple pharmacotherapeutic options, incidence rates for depressive disorders continue to rise. Nonpharmacological approaches (e.g., cognitive and behavioral therapies) exhibit encouraging efficacy rates; however, a lack of preclinical models has prevented progress in the identification of relevant neurobiological mechanisms of these approaches. Accordingly, the effort-based reward (EBR) preclinical model exposes rats to response-outcome (R-O) contingencies and provides an opportunity to investigate behavioral clinical approaches. In the current study, male and female rats were assigned to either an EBR contingent- or noncontingent-trained group and exposed to 7 weeks of training. Neuroadaptive cognitive responses were assessed in a cognitive uncertainty task (UT) and an object pattern separation task (OPST). Although no significant effects of EBR were observed in the UT, EBR contingent-trained rats approached the novel panel in the most difficult trial of the OPST faster than the noncontingent-trained group. Additionally, female EBR contingent-trained rats exhibited increased engagement with the novel stimulus panel across all trials. Examination of brain-derived neurotrophic factor (BDNF) in the lateral habenula (LHb), a putative neurobiological target for depressive symptoms, revealed lower BDNF immunoreactivity in EBR contingent-trained rats. Females in both training groups exhibited higher dehydroepiandrosterone/cortisol (DHEA/CORT) ratios, suggesting, along with the increased engagement with novel stimulus panels, that female rats may be more responsive to EBR contingency training than males. Together, these results suggest that EBR contingency training offers promise as a preclinical rat model for behavioral therapeutic interventions for depressive symptoms leading to a clearer understanding of putative neurobiological mechanisms.

Influences of Taurine Pharmacodynamics and Sex on Active Avoidance Learning and Memory.

Researchers have begun to direct their research to focus on the use of taurine as a psychopharmacotherapeutic compound to treat a wide range of health- related conditions as well as neuropathological diseases. Moreover, taurine has been shown to improve emotional and cognitive declines associated with senescence in neurotypical animal models. However, despite these advances in the field of taurine therapeutics, much less is known regarding the effects of sex and taurine on neurotypical animal models that are then manipulated, modified, and/or mutated to study human diseases. The present study sought to investigate this matter in a Long Evans Hooded rat model of mature age (i.e., postnatal day 60-90) in an active avoidance test (AAT). Rats were trained for 20 trials, given a 1 h. test break, retrained for another 20 trials, and then tested at 24 h, 48 h, and 1 week for learning and memory retention. An N = 63 rats were randomly assigned to three groups: (1) Control (n = 22), (2) Taurine Pre-Train (n = 19), and (3) Taurine Post-Train (n = 20). The aim of the present study was to determine the effects of taurine given 15 min before training when compared to being given after training but 15 min before testing at 24 h on learning and memory consolidation of the AAT. The results showed in Control rats that females had shorter latencies to cross in the shuttle box, increased rates of correct learning by the % Avoids/Escapes, and decreased rates of learning errors by the % Shocks. In Taurine Post-Train male rats, taurine treatment decreased their latency to cross in the shuttle box and their rate of learning errors by the % Shocks at 24 h and 48 h Testing, but it had no effect on their rate of correct learning by the % Avoids/Escapes when compared to Control and Taurine Pre-Train male rats. In contrast, Taurine Post-Train female rats increased their latency to cross in the shuttle box during Training, 24 h and 48 h Testing, when compared to the Control and Taurine Pre-Train female rats. Further, Taurine Post-Train female rats decreased their rate of learning % Avoids/Escapes and increased the rate of learning errors % Shocks when compared to Control female rats during Training and 24 h Testing but decreased their rate of learning % Avoids/Escapes and increased the rate of learning errors % Shocks when compared to Taurine Pre-Train female rats across all test conditions. These findings suggest that neurotypical female rats may be more sensitive to the aversive stimuli (i.e., foot shocks) used in the AAT as a motivating factor for learning that may cause paradoxical behavioral learning and memory patterns. This phenomenon raises an important concern for researchers to consider when studying learning and behavioral tests in rodents that use aversive and non-aversive stimuli or a combination of both such as in the AAT. Taurine, albeit neuroprotective, may not have as much benefit in a neurotypical animal model and may increase the susceptibility for anxiogenic behaviors and interfere with cognitive learning and memory behaviors. Therefore, the mechanistic way(s) in which taurine can treat, recovery, ameliorate, and forestall other neuropathological diseases in animal models may have different psychopharmacodynamics and psychopharmacokinetics in a neurotypical animal model and should be studied with caution. This does not preclude the continued investigation of taurine psychopharmacotherapies for neuropathological diseases but encourages the careful investigation of taurine supplementation and treatment in neurotypical animals as paradoxical behavioral and cognitive outcomes have been observed herein.

Developmental Lead Exposure in Rats Causes Sex-Dependent Changes in Neurobiological and Anxiety-Like Behaviors that Are Improved by Taurine Co-treatment.

Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance by disrupting the development of the GABAergic systems. These GABAergic disruptions have persistent neurobiological and neurobehavioral structure-function relationships that can be examined using animal models of Pb2+ exposure. Further, taurine, a GABA-AR agonist, has been shown to offer neuroprotection against neurodevelopmental Pb2+ exposure and senescence. The present study evaluated the effects of Pb2+ exposure (i.e., at 150 ppm and 1,000 ppm doses) on Long Evans hooded rats during the perinatal period of development on locomotor activity in the open field (OF) and anxiety-like behaviors in the elevated plus maze (EPM). This was followed by an examination of brain mass using an encephalization quotient (EQ) and isotropic fractionation (ITF) of total cells and the number of neurons and non-neuronal cells in the prefrontal cortex, hippocampus, and diencephalon. The results suggest that neurodevelopmental Pb2+ exposure caused persistent anxiety-like behaviors in both the OF and EPM with associated changes in EQ, but not ITF-determined cell density. Further, taurine treatment was observed to compensate for Pb2+ exposure in the behavioral assessments although precise neurobiological mechanisms remain unknown. Thus, more work is required to evaluate the role of taurine and other anxiolytic compounds in the alleviation of neurotoxicant-induced neurobehavioral syndromes and their associated neurobiological correlates.

In Vivo Sex-Dependent Effects of Perinatal Pb2+ Exposure on Pilocarpine-Induced Seizure Susceptibility and Taurine Neuropharmacology.

Lead (Pb2+) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain's excitation-to-inhibition (E/I) balance. This finding suggests that neurodevelopmental Pb2+ exposures may increase the risk of brain excitability and/or seizure susceptibility. Prior studies have suggested that neurodevelopmental Pb2+ exposures may cause excitotoxicity of cholinergic neurons, but little to no research has further investigated these potential relationships. The present study sought to evaluate the potential for perinatal neurodevelopmental Pb2+ exposures of 150 ppm and 1000 ppm on pilocarpine-induced seizures through the M1 receptor. The study also evaluated the potential for sex- and treatment-dependent differences in brain excitability. The study revealed that Control females have elevated cholinergic brain excitability and decreased GABAergic inhibition in response to pilocarpine-induced seizures. At low Pb2+ exposures, males exhibited more cholinergic brain excitability, whereas at higher Pb2+ exposures, females exhibited more cholinergic brain excitability. Further, taurine was able to provide neuroprotection against pilocarpine-induced seizures in males, whereas females did not reveal such observations. Thus, the present study adds new insights into the potential for cholinergic seizure susceptibility as a function of sex and the dosage ofneurodevelopmental Pb2+ exposure and how taurine may provide selective pharmacodynamics to treat or recover cholinergic system aberrations induced by neurotoxicants.

Taurine-Derived Compounds Produce Anxiolytic Effects in Rats Following Developmental Lead Exposure.

Lead (Pb2+) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain's excitation-to-inhibition (E/I) balance. Taurine is a well-established neuroprotective and inhibitory compound for regulating brain excitability. Since mechanistically taurine can facilitate neuronal inhibition through the GABA-AR, the present study examined the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1,000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random drug assignments to either saline, taurine, or taurine-derived compound (TD-101, TD-102, or TD-103) to assess the rats' responsivity to each drug in mitigating the developmental Pb2+-exposure and anxiety-like behaviors through the GABAergic system. Long-Evans hooded rats were assessed using an open field (OF) test for preliminary locomotor assessment. Twenty-four hours later, the same rats were exposed to the elevated plus maze (EPM) and were given an i.p. injection of 43 mg/Kg of the saline, taurine, or TD drugs 15 min prior to testing. Each rat was tested using the triple-blind random assignment method for each drug condition. The OF data revealed that Control female rats had increased locomotor activity over Control male rats, and the Pb2+-exposed males and females had increased locomotor activity when compared to the Control male and female rats. However, in the EPM, the Control female rats exhibited more anxiety-like behaviors over Control male rats, and the Pb2+-exposed male and female rats showed selective responsivity to TD drugs when compared to taurine. For Pb2+-exposed males, TD-101 showed consistent recovery of anxiety-like behaviors similar to that of taurine regardless of Pb2+ dose, whereas in Pb2+-exposed females TD-101 and TD-103 showed greater anxiolytic responses in the EPM. The results from the present psychopharmacological study suggests that taurine and its derivatives are interesting drug candidates to explore sex-specific mechanisms and actions of taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for neurodevelopmental Pb2+ exposure.

Performance and ruminal and intestinal morphometry of Santa Inês sheep submitted to feed restriction and refeeding.

A study was carried out to evaluate the performance and ruminal and intestinal morphology of Santa Inês sheep subjected to feed restriction followed by refeeding. A total of 40 uncastrated lambs with an approximate age of 120 ± 15 days and mean body weight (BW) of 17.04 ± 1.18 kg were randomly divided into two groups of BW (20 and 25 kg of BW), which were subjected to different levels of feed restriction (0%, 25%, and 40% of feed restriction). For performance variables, six treatments were considered (0, 25%, and 40% of feed restriction for both groups (20 and 25 kg of BW)) and five treatments for morphometric variables (ad libitum, 25% and 40% for both groups (20 and 25 kg of BW)). All animals were slaughtered with 14 weeks of experimentation. During the feed restriction phase, the dry matter intake (DMI), feed efficiency (FE), and average daily gain (ADG) decreased (P < 0.05) as the level of restriction increased. During the refeeding phase, lambs with 20 kg of body weight subjected to restriction presented lower (P < 0.05) DMI in the ad libitum treatment. However, lambs with 25 kg of body weight under feed restriction presented DMI, FE, and ADG similar (P > 0.05) to the group ad libitum. The final body weight of restricted lambs after refeeding (both groups 20 and 25 kg of body weight) was lower (P < 0.05) than lambs feed ad libitum. In relation to morphology, restricted lambs showed greater height ruminal papillae and larger (P < 0.05) area of ruminal absorption and intestinal absorption, especially the lambs under treatment 40% of feed restriction. The feed restriction followed by refeeding in sheep provided partial compensatory gain, in addition, caused morphological changes in the rumen and intestine that allowed greater absorption and possibly compensatory gain in periods of greater refeeding.

Mineral requirements for weight gain in growing male Santa Inês and Morada Nova hair sheep.

This study estimated the net macro and micromineral requirement from the 48 male uncastrated lambs (24 growing male Santa Inês and 24 growing male Morada Nova hair sheep), with initial weights of 21.7 ± 1.2 kg and 20.8 ± 0.8 kg using the comparative slaughter method. The experimental diet consisted of 30% forage (Buffel-Cenchrus ciliaris (L) hay) and 70% concentrate (corn grain 43.5%, soybean meal 22.0%, vegetable oil 3.0% and mineral supplement 1.5%). The experimental design was a completely randomized with two breeds, four weights, and six replicate. Mineral requirements sufficient to promote weight gain in Santa Inês sheep ranged from 1.75 to 1.03 g Ca, 1.01 to 0.61 g of P, 0.38 to 0.21 g of K, 0.38 to 0.16 of Na, 0.10 to 0.06 Mg, 28.5 to 16.0 mg of Fe, 6.14 to 3.22 mg of Cu, and Zn 23.0 to 14.0 mg/kg per unit of empty body weight (EBW) gain. In the Morada Nova breed, the requirements ranged from 1.96 to 0.84 g of Ca, 1.15 to 0.46 of P, 0.39 to 0.19 of K, 0.28 to 0.13 of Na, 0.10 to 0.05 Mg, 26.2 to 12.9 mg of Fe, 5.59 to 2.46 Cu, and Zn 23.6 to 10.3 mg/kg of EBW gain. Mineral requirements varied mainly in accordance with the proportion of bone mass and fat concentration in the carcass, which were influenced by the slaughter weight of the animals, and therefore should be used in the formulation of dietary mineral supplements.

Effect of the Use of Tomato Pomace on Feeding and Performance of Lactating Goats.

The aim of this research was to evaluate the effect of including different levels of tomato pomace (TP) on performance, blood biochemical parameters, hormones, production and composition of milk, and economic analysis of Saanen goats reared in confinement. Sixteen multiparous goats (Saanen), 21 days in milk, were randomly distributed in two Latin square 4 × 4 (four periods and four treatments), according to the inclusion levels of dehydrated tomato pomace (0%, 20%, 40%, and 60%) in the diet. This inclusion resulted in differences in the intake of dry and organic matter, as well as ether extract, crude protein, water, neutral detergent fiber, and non-fibrous carbohydrates. The inclusion of 60% TP resulted in a significant decrease of body weight (-4.42 kg) in comparison with initial body weight, while the other three treatments did not affect or increase the animal body weight (between -0.05 and +3.07 kg). The addition of 20% and 40% of TP resulted in higher milk production (around 1.5 kg day-1) than in animals from a control (1.2 kg day-1) and 60% TP (1.04 kg day-1). This increase was approximately 28% in the animals with 40% of TP inclusion. Moreover, the addition of 20% or 40% TP also improved the milk quality, which presented a higher fat amount (4.37% and 4.63% in 20% TP and 40% TP animals, respectively) than in a control (3.7%) and animals feed with 60% TP (4.02%). The feed efficiency and feed conversion did not show differences between diets. Thyroid hormones (T3 and T4) were also significantly affected by the inclusion of TP in the diet. The diet with the highest level of TP (60%) had the lowest cost per kilo among the diets evaluated. However, the use of 40% TP in animal diet presented the highest milk production and intermediate production cost.

Biochemical and hormonal parameters of lambs using guava (Psidium guajava L.) agro-industrial waste in the diet.

The objective of this research was to evaluate the biochemical and hormonal parameters of Santa Inês sheep that received diets with different levels of guava agro-industrial waste (GAW). Forty non-castrated male animals of the Santa Inês breed were used, with an average initial weight of 21.3 ± 2.6 kg, and an average age of 120 days. The animals were distributed in a completely randomized design, with five treatments and eight replicates, and fed with increasing GAW levels replacing hay (0.0, 7.5, 15.0, 22.5 and 30.0%). After the beginning of the diet period, blood samples were collected every 2 weeks approximately 3 h after feeding. Cholesterol concentration had a significant effect (P < 0.01) with the inclusion of GAW. The animals that ingested the control diet had the highest concentrations of cholesterol. T3 and T4 hormones showed a significant difference (P < 0.01) among the treatments, i.e. the animals that ingested the control diet had the lowest concentrations of these hormones. We concluded that the inclusion of GAW in up to 30% decreases the concentration of cholesterol and increases the concentrations of T3 and T4 in the blood, aiding the metabolism of the animals.

The fatty acid profile of fat depots from Santa Inês sheep fed spineless cactus (Opuntia ficus-indica Mill.).

BACKGROUND: Fat is the tissue that varies most in animals from both a quantitative and distribution perspective. It plays a fundamental biological role as energy storage during food scarcity. Renal, pelvic and internal fat are deposited first. These fats are used to identify fatty acid profiles that may be considered beneficial or unhealthy. The aim of this study is to evaluate the fatty acid profile of fat depots in Santa Inês sheep finished in confinement with spineless cactus in their diets. RESULTS: The treatments included increasing levels of spineless cactus (Opuntia fícus-indica Mill.): T1 = 0%, T2 = 30%, T3 = 50%, and T4 = 70%. The diets significantly affected the adipose depots. The orthogonal contrast between the diet with no cactus (control) and the other diets indicates that the quantity of saturated fatty acids decreased and that the levels of mono-unsaturated and polyunsaturated fatty acids increased in animals fed spineless cactus. CONCLUSION: The use of spineless cactus in the diets of Santa Inês sheep affects the lipid profile of their fat depots, reducing the quantity of saturated fatty acids and increasing the quantity of mono-unsaturated and polyunsaturated fatty acids. The fatty acid profile of the fat depots indicates that these fats can be used to formulate meat products and add economic and nutritional value to such products, which increases sheep farmers' incomes. © 2017 Society of Chemical Industry.

Physicochemical and sensory characteristics of yoghurts made from goat and cow milk.

Substituting goats' milk for cows' milk could improve the quality of dairy products, because it adds new sensorial characteristics. The aim of this study was to develop a type of yoghurt using goats' milk (25, 50, 75 and 100%) in place of cows' milk and to compare their characteristics. Physicochemical, microbiological and sensory characteristics were evaluated using a nine-point hedonic scale and purchase intention test. The data obtained in the physicochemical analysis were submitted to regression analysis and the sensory results were evaluated through analysis of variance. Among the physicochemical characteristics of the yoghurts, variation (P < 0.05) of ash, acidity and lactose was observed. Tasters in the sensory analysis indicated that yoghurts up to 50% of goats' milk received favorable averages; with lower scores for higher goats' milk concentrations (75% and 100%). No difference was reported in acidity. Replacing cows' milk with goats' milk in yoghurt preparation promotes variations in the physicochemical characteristics for ash, acidity and lactose. However, it does not cause alterations in the sensory attributes (50% goat milk) and therefore could be considered as an alternative for the production of dairy products. © 2016 Japanese Society of Animal Science.

Eliminating tobacco-related disparities among Pacific Islanders through leadership and capacity building: promising practices and lessons learned.

Tobacco remains a major risk factor for premature death and ill health among Pacific Islanders, and tobacco-related disparities persist. Eliminating these disparities requires a comprehensive approach to transform community norms about tobacco use through policy change, as contained in the World Health Organization international Framework Convention on Tobacco Control. Three of the six U.S.-affiliated Pacific Islands-the Federated States of Micronesia, Palau, and the Marshall Islands-are Parties to the Framework; the remaining three territories-American Samoa, the Commonwealth of the Northern Mariana Islands, and Guam-are excluded from the treaty by virtue of U.S. nonratification. Capacity building and leadership development are essential in achieving policy change and health equity within Pacific Islander communities. We describe promising practices from American Samoa, the Commonwealth of the Northern Mariana Islands, the Federated States of Micronesia, Guam, and Palau and highlight some of the key lessons learned in supporting and sustaining the reduction in tobacco use among Pacific Islanders as the first step toward eliminating tobacco-related disparities in these populations.

Características microbiológicas, físico-químicas e sensoriais de "almôndegas" à base de polpa de Tilápia (Oreochromis niloticus) / Microbiological, physicochemical and sensory characteristics of pulp-of-Tilapia-based (Oreochromis niloticus) meatballs

O consumo mundial per capita de pescado e produtos derivados vem crescendo gradualmente nas últimas décadas. Este trabalho teve como objetivo elaborar um reestruturado, tipo almôndegas, utilizando-se polpa bruta de tilápia (Oreochromis niloticus - PBT) e proteína texturizada de soja (PTS). Para obtenção do reestruturado, o PTS, de coloração marrom e sabor carne, teve sua concentração variada nos diferentes tratamentos: 0, 5 e 2,5% de PTS em T1, T2 e T3, respectivamente. Foram realizadas análises microbiológicas e físico-químicas da matéria prima e das ?almôndegas?; a análise sensorial foi realizada somente no produto final. Os resultados das análises microbiológicas da polpa e das ?almôndegas? estavam dentro dos padrões exigidos pela legislação brasileira. Os parâmetros físico-químicos não apresentaram muitas alterações e também estavam de acordo com os padrões exigidos para alimentos. As ?almôndegas? elaboradas com 5% PTS (T2) mostraram menores valores para a capacidade de retenção de água e perda de peso por cocção. No teste de aceitação das ?almôndegas? não houve diferença significativa (p? 0,05) entre os tratamentos, com aceitabilidade acima de 70% para todos os atributos avaliados. O teste de intenção de compra mostrou que mais de 50% dos consumidores que participaram do teste tinham a intenção de comprar os produtos, se os encontrasse à venda. O processo de elaboração das ?almôndegas? à base polpa de tilápia foi obtido com sucesso, sendo que o melhor tratamento foi o que continha 5%de PTS.

Worldwide per capita consumption of fish and derivative products has been increasing gradually in the last few decades. This study aimed to formulate a restructured product, like meatballs, using gross pulp of tilapia (Oreochromis niloticus ? GPT) and textured protein of soybean (TPS). In order to achieve the restructured product, brown-colored and meat-flavored, TPS had its concentration diversified in the different treatments: 0.5 and 2.5% of TPS in T1, T2 and T3, respectively. Microbiological and physiochemical analyses of raw material and meatballs were carried out; the sensory analysis was carried out only with the final product. The results of microbiological analyses of the pulp and meatballs fit the patterns demanded by Brazilian legislation. Physiochemical parameters did not show many alterations and also fit the patterns demanded for food. ?Meatballs? formulated with 5% TPS (T2) showed lower values for the capacity of water and cooking-loss-of-weight retention. In the acceptance test of ?meatballs? there was no significant difference (p? 0,05) among treatments, with acceptability higher than 70% for all the evaluated attributes. The test of purchase intent showed that over 50% of consumers who took part in the test had the intention of buying the products if they were for sale. The process of elaboration of the pulp-of-tilapia-based ?meatballs? was successful, once the best treatment was the one which contained TPS 5%.

Nurse requirement planning: a computer-based model.

RATIONALE: The paper considers the recent debate on mandating patient-nurse ratios in inpatient units of hospitals, and highlights the need for a comprehensive approach to requirement estimation, which can facilitate the implementation of mandated patient-nurse ratios in hospitals. AIM: After considering the available methods for nurse requirement planning, this paper intends to discuss an alternative approach for estimating nurse requirement when certain patient-nurse ratios have been prescribed. METHODS: Once the required information becomes available, the next task is to estimate unit-wise and overall nurse requirement. As the computational effort is quite considerable, the paper develops and elucidates a computer-assisted nurse requirement-planning model, which helps in systematizing and accelerating the estimation process. RESULTS: The computer-based nurse requirement-planning model enables planners to respond objectively and promptly to requests for more nurses by nursing administrators (who perceive nurse shortages). CONCLUSIONS: The paper demonstrates the unique advantage of this computer-based approach over conventional methods, especially when the planner wishes to pre-evaluate alternative decision options by simulating manpower implications under alternative scenarios.