Differential effects of high-fat diet on endocrine, metabolic and depressive-like behaviors in male and female rats.

The complications of obesity extend beyond the periphery to the central nervous system (CNS) and include an increased risk of developing neuropsychiatric co-morbidities like depressive illness. Preclinical studies support this concept, including studies that have examined the effects of a high-fat diet (HFD) on depressive-like behaviors. Although women are approximately two-fold more likely to develop depressive illness compared to men, most preclinical studies have focused on the effects of HFD in male rodents. Accordingly, the goal of this study was to examine depressive-like behaviors in male and female rats provided access to a HFD. In agreement with prior studies, male and female rats provided a HFD segregate into an obesity phenotype (i.e., diet-induced obesity; DIO) or a diet resistant (DR) phenotype. Upon confirmation of the DR and DIO phenotypes, behavioral assays were performed in control chow, DR, and DIO rats. In the sucrose preference test, male DIO rats exhibited significant decreases in sucrose consumption (i.e., anhedonia) compared to male DR and male control rats. In the forced swim test (FST), male DIO rats exhibited increases in immobility and decreases in climbing behaviors in the pre-test sessions. Interestingly, male DR rats exhibited these same changes in both the pre-test and test sessions of the FST, suggesting that consumption of a HFD, even in the absence of the development of an obesity phenotype, has behavioral consequences. Female rats did not exhibit differences in sucrose preference, but female DIO rats exhibited increases in immobility exclusively in the test session of the FST, behavioral changes that were not affected by the stage of the estrous cycle. Collectively, these studies demonstrate that access to a HFD elicits different behavioral outcomes in male and female rats.

Adaptations to water stress and pastoralism in the Turkana of northwest Kenya.

The Turkana people inhabit arid regions of east Africa-where temperatures are high and water is scarce-and they practice subsistence pastoralism, such that their diet is primarily composed of animal products. Working with Turkana communities, we sequenced 367 genomes and identified 8 regions putatively involved in adaptation to water stress and pastoralism. One of these regions includes a putative enhancer for STC1-a kidney-expressed gene involved in the response to dehydration and the metabolism of purine-rich foods such as red meat. We show that STC1 is induced by antidiuretic hormone in humans, is associated with urea levels in the Turkana themselves, and is under strong selection in this population (s∼0.041). This work highlights that partnerships with subsistence-level groups can lead to new models of human physiology with biomedical relevance.

Validation of and Normative Data of the DVAQ-30, a New Video-Naming Test for Assessing Verb Anomia.

OBJECTIVE: Anomia is usually assessed using picture-naming tests. While many tests evaluate anomia for nouns, very few tests have been specifically designed for verb anomia. This article presents the DVAQ-30, a new naming test for detecting verb anomia in adults and elderly people. METHOD: The article describes three studies. Study 1 focused on the DVAQ-30 development phase. In Study 2, healthy participants and individuals with post-stroke aphasia, mild cognitive impairment, Alzheimer's disease, or primary progressive aphasia were assessed using the DVAQ-30 to establish its convergent and discriminant validity, test-retest reliability, and internal consistency. In Study 3, a group of adults and elderly Quebec French-speaking adults were assessed to obtain normative data. RESULTS: The DVAQ-30 had good convergent validity and distinguished the performance of healthy participants from that of participants with pathological conditions. The test also had good internal consistency, and the test-retest analysis showed that the scores had good temporal stability. Furthermore, normative data were collected on the performance of 244 participants aged 50 years old and over. CONCLUSIONS: The DVAQ-30 fills an important gap and has the potential to help clinicians and researchers better detect verb anomia associated with pathological aging and post-stroke aphasia.

Training Programs Designed for Muscle Hypertrophy in Bodybuilders: A Narrative Review.

Bodybuilding is a sport that requires adequate training strategies in order to maximize skeletal muscle hypertrophy. The purpose of the present review was to perform a narrative assessment of the training routines designed for muscle hypertrophy used by bodybuilders. A search was carried out in the databases Pubmed/MEDLINE, Scielo, EBSCO, LILACS, SportDiscus, Web of Science, and CINAHL with the words "Resistance training" and "hypertrophy" in bodybuilders and their variations that involve the respective outcomes. Fourteen studies were identified that investigated the long-term training routines of bodybuilders. These studies demonstrate a pattern in the training organization, whereby there is a separation of training into four distinct periods: off-season, pre-contest, peak week, and post-contest. Each period has a specific spectrum of intensity load, total training volume, and exercise type (multi- or single-joint). We conclude that bodybuilding competitors employed a higher intensity load, lower number of repetitions, and longer rest intervals in the off-season than pre-contest.

The role of semantic memory in the recognition of emotional valence conveyed by written words.

The main goal of this study was to examine the role of semantic memory in the recognition of emotional valence conveyed by words. Eight participants presenting with the semantic variant of primary progressive aphasia (svPPA) and 33 healthy control participants were administered three tasks designed to investigate the formal association between the recognition of emotional valence conveyed by words and the lexical and semantic processing of these words. Results revealed that individuals with svPPA showed deficits in the recognition of negative emotional valence conveyed by words. Moreover, results evidenced that their performance in the recognition of emotional valence was better for correctly than for incorrectly retrieved lexical entries of words, while their performance was comparable for words that were correctly or incorrectly associated with semantic concepts. These results suggest that the recognition of emotional valence conveyed by words relies on the retrieval of lexical, but not semantic, representations of words.

Carbohydrate Loading Practice in Bodybuilders: Effects on Muscle Thickness, Photo Silhouette Scores, Mood States and Gastrointestinal Symptoms.

A common practice among bodybuilders is the use of carbohydrate loading to improve physical appearance during competition, while limited documented data is available about this issue. The aim of the present study was to evaluate muscle thickness, mood states, gastrointestinal symptoms and subjective silhouette assessment following carbohydrate loading in bodybuilders. Twenty-four male bodybuilders were evaluated at the weighing period following three days of carbohydrate depletion (M1), and 24h of carbohydrate loading leading up to the competition (M2), stratified into: no carbohydrate load (NC, n = 9) and carbohydrate loading (CL, n =1 5). The silhouette scale, Brunel mood scale (BRUMS), muscle thickness (ultrasound), circumferences, and gastrointestinal symptoms (GIS) were evaluated at M1 and M2. The NC displayed no differences in muscle thickness and circumferences between M1 and M2. Body mass, muscle thickness (elbow flexors, a combination of biceps brachii/ brachialis muscle, and triceps brachii) and circumferences (chest, hip, thigh, arm, calves, and forearm) increased significantly (p < 0.05) in the CL at M2. There was a significant increase in photo silhouette scores (p < 0.05) in the CL at M2. There was no significant difference in mood states between groups or time. The most reported GIS was constipation: 7/9 (NC) and 9/15 (CL) during M1 and 6/9 (NC), and 5/15 (CL) at M2 with symptoms described as 'moderate' or 'severe'. Diarrhea was reported by 7/15 CL (4/15 as severe). These data suggest that carbohydrate loading may contribute to an acute increase in muscle volume and physical appearance, however, it needs to be better planned to minimize gastrointestinal symptoms in bodybuilders.

Vinegar (acetic acid) intake on glucose metabolism: A narrative review.

Vinegar intake is considered a food item that improves blood glucose in humans. This review aimed to discuss studies that investigated the impact of vinegar intake on the glycemic profile in humans and the putative mechanistic cellular pathways in both human and animal models. A search of literature was performed on the Cochrane, MEDLINE and Web of Science databases for articles published between 1995 and 2018. There is considerable support for vinegar having a positive acute effect on blood glucose levels when combined with carbohydrate-rich meals. Conversely, there are few chronic interventions analyzing the impact of vinegar intake on blood glucose. Based on available evidence, we hypothesize three pathways by which vinegar may improve blood glucose: The inhibition of α-amylase action; increased glucose uptake; and mediation by transcription factors. When evaluating the current body of literature, daily vinegar intake in amounts of ∼10-30 mL (∼2-6 tablespoons) appear to improve the glycemic response to carbohydrate-rich meals; however, there is a paucity of studies investigating chronic effects of vinegar intake.

Pyridostigmine bromide and stress interact to impact immune function, cholinergic neurochemistry and behavior in a rat model of Gulf War Illness.

Gulf War Illness (GWI) is characterized by a constellation of symptoms that includes cognitive dysfunction. While the causes for GWI remain unknown, prophylactic use of the acetylcholinesterase inhibitor pyridostigmine bromide (PB) in combination with the stress of deployment has been proposed to be among the causes of the cognitive dysfunction in GWI. Mechanistically, clinical studies suggest that altered immune function may be an underlying factor in the neurochemical and neurobehavioral complications of GWI. Accordingly, the goal of this study was to determine how responses to an immune challenge (lipopolysaccharide; LPS) or stress impacts inflammation, acetylcholine (ACh) neurochemistry and behavior in an experimental model of GWI. Rats with a history of PB treatment exhibited potentiated increases in C-reactive protein levels in response to a submaximal LPS challenge compared to control rats, indicating that prior treatment with this cholinesterase inhibitor leads to exacerbated inflammatory responses to a subsequent immune challenge. ACh responses to LPS administration were decreased in the hippocampus, but not prefrontal cortex (PFC), in rats with a prior history of PB treatment or stress exposure. Additionally, ACh release in response to acute immobilization stress was attenuated in the PFC and hippocampus in these groups. These attenuated cholinergic responses were accompanied by impairments in contextual and cue-based fear learning. The results of this study suggest that stress and LPS challenges adversely affect central ACh neurochemistry in a rodent model of GWI and support the hypothesis that dysregulated immune responses are mechanistically linked to the neurological complications of GWI.

Pathophysiology in a model of Gulf War Illness: Contributions of pyridostigmine bromide and stress.

During the Gulf War, prophylactic treatment with pyridostigmine bromide (PB) along with the stress of deployment may have caused unexpected alterations in neural and immune function, resulting in a host of cognitive deficits which have become clinically termed Gulf War Illness (GWI). In order to test this interaction between PB and stress, the following study used a rodent model of GWI to examine how combinations of repeated restraint stress and PB induced alterations of peripheral cholinesterase (ChE) activity, corticosterone (CORT) levels, and cytokines on the last day of treatment, and then 10 days and three months post-treatment. Results indicate that PB decreases ChE activity acutely but sensitizes it by three months post-treatment selectively in rats subjected to stress. Similarly, while stress increased CORT levels acutely, rats in the PB/stressed condition continued to exhibit elevations in CORT at the delayed time point, indicating that PB and stress interact to progressively disrupt homeostasis in several peripheral measures. Because memory deficits are also common in clinical populations with GWI, we examined the effects of PB and stress on contextual fear conditioning. PB exacerbates stress-induced impairments in contextual fear conditioning ten days post-treatment, but protects against stress-induced augmentation of contextual fear conditioning at three months post-treatment. Collectively, these results provide critical insight as to how PB and stress may interact to contribute to the pathophysiological progression of GWI.

Characteristics of CA1 place fields in a complex maze with multiple choice points.

For the sake of rigorous control of task variables, hippocampal place cells have been usually studied in relatively simple environments. To approach the situation of real-life navigation in an urban-like environment, we recorded CA1 place cells while rats performance a memory task in a "Townmaze" with two start locations, three alternate paths in the maze midsection, followed by a two-way choice that determined the trial outcome, access to a goal compartment. Further, to test the ability of place cells to update their spatial representation upon local changes in the environment while maintaining the integrity of the overall spatial map to allow effective navigation, we occasionally introduced barriers in the maze mid-section to force the rat to select a nonpreferred route. The "Townmaze" revealed many new interesting features of CA1 neurons. First, we found neurons with 3-5 fields that appear to represent segments on a single common route through the maze. Second, we found neurons with 3-5 fields similarly aligned along the longitudinal or transverse maze axis. Responses to the barriers were assessed separately near and far from the barriers. Appearance of new fields in response to the barriers took place almost exclusively only locally near the barrier, whereas in-field firing rate changes occurred throughout the maze. Further, field location changes did not correlate with the task performance, whereas firing rate changes did. These findings suggest that in a complex environment with blocked distal views, CA1 neurons code for the environment as sequences of significant nodes but are also capable of extracting and associating common elements across these sequences.

Treinamento de potência em idosos: porque é importante? / Power training in the elderly: why is it important?

A redução da força e da potência são acontecimentos que fazem parte do processo de envelhecimento biológico com consequente redução da função muscular, tendo um forte impacto sobre as atividades da vida diária e saúde dos idosos. O aumento da potência muscular pode conduzir a aumentos na capacidade para realizar tarefas da vida diária, prevenir quedas, diminuir a dependência e deficiência na vida adulta. Para desenvolver potência é necessária uma carga mais alta assim como realizar os movimentos com velocidade mais rápida comparado aos exercícios tradicionais. Cargas altas, médias e leves são bem toleradas e seguras para idosos saudáveis. O treinamento de potência pode ser uma estratégia importante e útil para a prevenção e reabilitação dos declínios na força e da função muscular decorrentes do envelhecimento....(AU)

The decrease in muscle strength and power are part of the biological aging process accompanied by a decrease in muscle function, as it has a Strong impact in daily life activities and health of elderly subjects. The increase in muscle power may result in increased capacity to perform daily living activities, prevent falls, decrease dependency and deficiency in adult life. To develop power a higher load and higher velocity movements are necessary as compared to traditional training. High, medium and light loads are well tolerated and safe for health elderly subjects. Power training can be an important and useful strategy to prevent and rehabilitate the decline in muscle strength and function induced by aging....(AU)

Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease: Towards a better understanding of the semantic impairment.

While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimer's disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous-person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture-naming test of non-unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non-unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL>AD>svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous-person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post-hoc neuroimaging analyses also showed that famous-person naming impairments in AD correlated with atrophy in the temporo-parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients' impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically-unique-entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical-semantic deficits.

Leptin resistance elicits depressive-like behaviors in rats.

There is a growing appreciation that the complications of obesity extend to the central nervous system (CNS) and include increased risk for development of neuropsychiatric co-morbidities such as depressive illness. The neurological consequences of obesity may develop as a continuum and involve a progression of pathological features which is initiated by leptin resistance. Leptin resistance is a hallmark feature of obesity, but it is unknown whether leptin resistance or blockage of leptin action is casually linked to the neurological changes which underlie depressive-like phenotypes. Accordingly, the aim of the current study was to examine whether chronic administration of a pegylated leptin receptor antagonist (Peg-LRA) elicits depressive-like behaviors in adult male rats. Peg-LRA administration resulted in endocrine and metabolic features that are characteristic of an obesity phenotype. Peg-LRA rats also exhibited increased immobility in the forced swim test, depressive-like behaviors that were accompanied by indices of peripheral inflammation. These results demonstrate that leptin resistance elicits an obesity phenotype that is characterized by peripheral immune changes and depressive-like behaviors in rats, supporting the concept that co-morbid obesity and depressive illness develop as a continuum resulting from changes in the peripheral endocrine and metabolic milieu.

Akt/mTOR pathway contributes to skeletal muscle anti-atrophic effect of aerobic exercise training in heart failure mice.

BACKGROUND: Exercise intolerance is one of the main clinical symptoms of heart failure (HF) and is associated with skeletal muscle wasting due to an imbalance between proteolysis and protein synthesis. In this study, we tested whether aerobic exercise training (AET) would counteract skeletal muscle atrophy by activating IGF-I/Akt/mTOR pathway in HF mice. METHODS: Sympathetic hyperactivity induced HF mice were assigned into 8-week moderate intensity AET. Untrained wild type and HF mice were used as control. Soleus cross sectional area was evaluated by histochemistry and motor performance by rotarod. 26S proteasome activity was assessed by fluorimetric assay, and components of IGF-I/Akt/mTOR pathway or myostatin pathway by qRT-PCR or immunoblotting. A different subset of mice was used to evaluate the relative contribution of mTOR inhibition (rapamycin) or activation (leucine) on AET-induced changes in muscle mass regulation. RESULTS: AET prevented exercise intolerance and impaired motor performance in HF mice. These effects were associated with attenuation of soleus atrophy. Rapamycin treatment precluded AET effects on soleus mass in HF mice suggesting the involvement of IGF signaling pathway in this response. In fact, AET increased IGF-I Ea and IGF-I Pan mRNA levels, while it reduced myostatin and Smad2 mRNA levels in HF mice. At protein levels, AET prevented reduced expression levels of IGF-I, pAkt (at basal state), as well as, p4E-BP1 and pP70(S6K) (leucine-stimulated state) in HF mice. Additionally, AET prevented 26S proteasome hyperactivity in HF mice. CONCLUSIONS: Taken together, our data provide evidence for AET-induced activation of IGF-I/Akt/mTOR signaling pathway counteracting HF-induced muscle wasting.

Tissue damage negatively regulates LPS-induced macrophage necroptosis.

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules.

Selective expression of Narp in primary nociceptive neurons: role in microglia/macrophage activation following nerve injury.

Neuronal activity regulated pentraxin (Narp) is a secreted protein implicated in regulating synaptic plasticity via its association with the extracellular surface of AMPA receptors. We found robust Narp immunostaining in dorsal root ganglia (DRG) that is largely restricted to small diameter neurons, and in the superficial layers of the dorsal horn of the spinal cord. In double staining studies of DRG, we found that Narp is expressed in both IB4- and CGRP-positive neurons, markers of distinct populations of nociceptive neurons. Although a panel of standard pain behavioral assays were unaffected by Narp deletion, we found that Narp knockout mice displayed an exaggerated microglia/macrophage response in the dorsal horn of the spinal cord to sciatic nerve transection 3days after surgery compared with wild type mice. As other members of the pentraxin family have been implicated in regulating innate immunity, these findings suggest that Narp, and perhaps other neuronal pentraxins, also regulate inflammation in the nervous system.

Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis.

Macrophages can be activated and regulated by high-mobility group box 1 (HMGB1), a highly conserved nuclear protein. Inflammatory functions of HMGB1 are mediated by binding to cell surface receptors, including the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, TLR4, and TLR9. Pyroptosis is a caspase-1-dependent programmed cell death, which features rapid plasma membrane rupture, DNA fragmentation, and release of proinflammatory intracellular contents. Pyroptosis can be triggered by various stimuli, however, the mechanism underlying pyroptosis remains unclear. In this study, we identify a novel pathway of HMGB1-induced macrophage pyroptosis. We demonstrate that HMGB1, acting through RAGE and dynamin-dependent signaling, initiates HMGB1endocytosis, which in turn induces cell pyroptosis. The endocytosis of HMGB1 triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. We further confirm that HMGB1-induced macrophage pyroptosis also occurs in vivo during endotoxemia, suggesting a pathophysiological significance for this form of pyroptosis in the development of inflammation. These findings shed light on the regulatory role of ligand-receptor internalization in directing cell fate, which may have an important role in the progress of inflammation following infection and injury.

Anatomical substrates for direct interactions between hippocampus, medial prefrontal cortex, and the thalamic nucleus reuniens.

The reuniens nucleus in the midline thalamus projects to the medial prefrontal cortex (mPFC) and the hippocampus, and has been suggested to modulate interactions between these regions, such as spindle-ripple correlations during sleep and theta band coherence during exploratory behavior. Feedback from the hippocampus to the nucleus reuniens has received less attention but has the potential to influence thalamocortical networks as a function of hippocampal activation. We used the retrograde tracer cholera toxin B conjugated to two fluorophores to study thalamic projections to the dorsal and ventral hippocampus and to the prelimbic and infralimbic subregions of mPFC. We also examined the feedback connections from the hippocampus to reuniens. The goal was to evaluate the anatomical basis for direct coordination between reuniens, mPFC, and hippocampus by looking for double-labeled cells in reuniens and hippocampus. In confirmation of previous reports, the nucleus reuniens was the origin of most thalamic afferents to the dorsal hippocampus, whereas both reuniens and the lateral dorsal nucleus projected to ventral hippocampus. Feedback from hippocampus to reuniens originated primarily in the dorsal and ventral subiculum. Thalamic cells with collaterals to mPFC and hippocampus were found in reuniens, across its anteroposterior axis, and represented, on average, about 8 % of the labeled cells in reuniens. Hippocampal cells with collaterals to mPFC and reuniens were less common (~1 % of the labeled subicular cells), and located in the molecular layer of the subiculum. The results indicate that a subset of reuniens cells can directly coordinate activity in mPFC and hippocampus. Cells with collaterals in the hippocampus-reuniens-mPFC network may be important for the systems consolidation of memory traces and for theta synchronization during exploratory behavior.

Shot-noise-limited monitoring and phase locking of the motion of a single trapped ion.

We perform a high-resolution real-time readout of the motion of a single trapped and laser-cooled Ba+ ion. By using an interferometric setup, we demonstrate a shot-noise-limited measurement of thermal oscillations with a resolution of 4 times the standard quantum limit. We apply the real-time monitoring for phase control of the ion motion through a feedback loop, suppressing the photon recoil-induced phase diffusion. Because of the spectral narrowing in the phase-locked mode, the coherent ion oscillation is measured with a resolution of about 0.3 times the standard quantum limit.

Evaluation of Tier 5 Medical Training Initiative opportunities in dentistry.

This paper reviews the first two years of overseas postgraduate dental placements in the UK under the Medical Training Initiative (MTI), which is part of Tier 5 government authorised exchange. Details of the objectives of the programme, the trainees appointed, specialty areas studied and length of training are described. The methods used for assessing the training are reported. It is concluded that the objectives of the MTI have been met in dentistry and that Tier 5 provides a valuable opportunity for establishing international links in postgraduate clinical dentistry.