Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

The Src inhibitor dasatinib accelerates the differentiation of human bone marrow-derived mesenchymal stromal cells into osteoblasts

The proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially developed for the treatment of chronic myeloid leukemia. It has also shown promising results in preclinical studies in various solid tumors. However, its effects on the differentiation of human osteoblasts have never been examined.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: Preliminary report

BACKGROUND: Vestibular rehabilitation (VR) is a well-accepted exercise program intended to remedy balance impairment caused by damage to the peripheral vestibular system. Alternative therapies, such as Tai Chi (TC), have recently gained popularity as a treatment for balance impairment. Although VR and TC can benefit people with vestibulopathy, the degree to which gait improvements may be related to neuromuscular adaptations of the lower extremities for the two different therapies are unknown. METHODS: We examined the relationship between lower extremity neuromuscular function and trunk control in 36 older adults with vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance measures (gait speed, step length, stance duration and step width), lower extremity sagittal plane mechanical energy expenditures (MEE), and trunk sagittal and frontal plane kinematics (peak and range of linear and angular velocity), were measured. RESULTS: Although gait time-distance measures were improved in both groups following treatment, no significant between-groups differences were observed for the MEE and trunk kinematic measures. Significant within groups changes, however, were observed. The TC group significantly increased ankle MEE contribution and decreased hip MEE contribution to total leg MEE, while no significant changes were found within the VR group. The TC group exhibited a positive relationship between change in leg MEE and change in trunk velocity peak and range, while the VR group exhibited a negative relationship. CONCLUSION: Gait function improved in both groups consistent with expectations of the interventions. Differences in each group's response to therapy appear to suggest that improved gait function may be due to different neuromuscular adaptations resulting from the different interventions. The TC group's improvements were associated with reorganized lower extremity neuromuscular patterns, which appear to promote a faster gait and reduced excessive hip compensation. The VR group's improvements, however, were not the result of lower extremity neuromuscular pattern changes. Lower-extremity MEE increases corresponded to attenuated forward trunk linear and angular movement in the VR group, suggesting better control of upper body motion to minimize loss of balance. These data support a growing body of evidence that Tai Chi may be a valuable complementary treatment for vestibular disorders

RANK, RANKL and osteoprotegerin in bone biology and disease

Upon the discovery of RANK, RANKL and OPG in the late 1990s, their importance in the maintenance of the skeletal structure and their dramatic role in bone disease were largely unexpected. In recent years the understanding of these proteins, in particular their regulation, has greatly increased. This review aims to bring the interested reader up to date with the latest news and views on the mechanisms controlling bone resorption in normal and pathological conditions

Metabolic syndrome in overweight children from the city of Botucatu - São Paulo State - Brazil: agreement among six diagnostic criteria

<p>Abstract</p> <p>Background</p> <p>The metabolic syndrome has been described in children; however, a standard criterion has not been established for its diagnosis. Also, few studies have been conducted to specifically observe the possible existence of agreement among the existing diagnostic criteria. The purpose of the study is to evaluate agreement concerning prevalence rates of the metabolic syndrome diagnosed by six different criteria in overweight schoolchildren in the city of Botucatu - SP -Brazil.</p> <p>Methods</p> <p>This is a cross-sectional study on 128 overweight schoolchildren. Clinical examination included anthropometry, pubertal staging evaluation, and blood pressure. Triacylglycerol, glycemia, HDL-cholesterol, insulin levels, and HOMA-IR were determined. The Kappa index, the Mann-Whitney test and the chi-square test were used for statistical analysis.</p> <p>Results</p> <p>The prevalence of the metabolic syndrome varied from 10 to 16.5% according to different diagnostic criteria. Results were similar for boys and girls and pubertal stage. Great agreement was observed among the six different diagnostic criteria for the metabolic syndrome.</p> <p>Conclusions</p> <p>Different diagnostic criteria, when adopted for subjects with similar demographic characteristics, generate similar and compatible prevalence. Results suggest that it is possible to adopt any of the analyzed criteria, and the choice should be according to the components available for each situation.</p

Non-pharmacological management of osteoporosis: a consensus of the Belgian Bone Club

This consensus article reviews the various aspects of the non-pharmacological management of osteoporosis, including the effects of nutriments, physical exercise, lifestyle, fall prevention, and hip protectors. Vertebroplasty is also briefly reviewed. Non-pharmacological management of osteoporosis is a broad concept. It must be viewed as an essential part of the prevention of fractures from childhood through adulthood and the old age. The topic also includes surgical procedures for the treatment of peripheral and vertebral fractures and the post-fracture rehabilitation. The present document is the result of a consensus, based on a systematic review and a critical appraisal of the literature. Diets deficient in calcium, proteins or vitamin D impair skeletal integrity. The effect of other nutriments is less clear, although an excessive consumption of sodium, caffeine, or fibres exerts negative effects on calcium balance. The deleterious effects of tobacco, excessive alcohol consumption and a low BMI are well accepted. Physical activity is of primary importance to reach optimal peak bone mass but, if numerous studies have shown the beneficial effects of various types of exercise on bone mass, fracture data as an endpoint are scanty. Fall prevention strategies are especially efficient in the community setting, but less evidence is available about their effectiveness in preventing fall-related injuries and fractures. The efficacy of hip protectors remains controversial. This is also true for vertebroplasty and kyphoplasty. Several randomized controlled studies had reported a short-term advantage of vertebroplasty over medical treatment for pain relief, but these findings have been questioned by recent sham-controlled randomized clinical studies

Nicotinamide's Ups and Downs:Consequences for Fertility, Development, Longevity and Diseases of Poverty and Affluence

Aims and Scope: To further explore the role of dietary nicotinamide in both brain development and diseases, particularly those of ageing. Articles cover neurodegenerative disease and cancer. Also discussed are the effects of nicotinamide, contained in meat and supplements and derived from symbionts, on the major transitions of disease and fertility from ancient times up to the present day. A key role for the tryptophan – NAD ‘de novo’ and immune tolerance pathway are discussed at length in the context of fertility and longevity and the transitions from immune paresis to Treg-mediated immune tolerance and then finally to intolerance and their associated diseases. Abstract: Nicotinamide in human evolution increased cognitive power in a positive feedback loop originally involving hunting. As the precursor to metabolic master molecule NAD it is, as vitamin B3, vital for health. Paradoxically, a lower dose on a diverse plant then cereal-based diet fuelled population booms from the Mesolithic onwards, by upping immune tolerance of the foetus. Increased tolerance of risky symbionts, whether in the gut or TB, that excrete nicotinamide co-evolved as buffers for when diet was inadequate. High biological fertility, despite disease trade-offs, avoided the extinction of Homo sapiens and heralded the dawn of a conscious, creative, and pro-fertility culture. Nicotinamide equity now would stabilise populations and prevent NAD-based diseases of poverty and affluence