Iron-deficient diet induces distinct protein profile related to energy metabolism in the striatum and hippocampus of adult rats.

Iron deficiency is a public health problem that affects all age groups. Its main consequence is anemia, but it can also affect cognitive functions. Although the negative effects of iron deficiency on cognitive function have been extensively described, the underlying mechanism has not been fully investigated. Thus, to gain an unbiased insight into the effects of iron deficiency (ID) on discrete brain regions, we performed a proteomic analysis of the striatum and hippocampus of adult rats subjected to an iron restricted (IR) diets for 30 days. We found that an IR diet caused major alterations in proteins related to glycolysis and lipid catabolism in the striatum. In the hippocampus, a larger portion of proteins related to oxidative phosphorylation and neurodegenerative diseases were altered. These alterations in the striatum and hippocampus occurred without a reduction in local iron levels, although there was a drastic reduction in liver iron and ferritin. Moreover, the IR group showed higher fasting glycaemia than the control group. These results suggest that brain iron content is preserved during acute iron deficiency, but the alterations of other systemic metabolites such as glucose may trigger distinct metabolic adaptations in each brain region. Abnormal energy metabolism precedes and persists in many neurological disorders. Thus, altered energy metabolism can be one of the mechanisms by which iron deficiency affects cognitive functions.

Sleep deprivation regulates availability of PrPC and Aß peptides which can impair interaction between PrPC and laminin and neuronal plasticity.

PrPC is a glycoprotein capable to interact with several molecules and mediates diverse signaling pathways. Among numerous ligands, laminin (LN) is known to promote neurite outgrowth and memory consolidation, while amyloid-beta oligomers (Aßo) trigger synaptic dysfunction. In both pathways, mGluR1 is recruited as co-receptor. The involvement of PrPC /mGluR1 in these opposite functions suggests that this complex is a key element in the regulation of synaptic activity. Considering that sleep-wake cycle is important for synaptic homeostasis, we aimed to investigate how sleep deprivation affects the expression of PrPC and its ligands, laminin, Aßo, and mGluR1, a multicomplex that can interfere with neuronal plasticity. To address this question, hippocampi of control (CT) and sleep deprived (SD) C57BL/6 mice were collected at two time points of circadian period (13 hr and 21 hr). We observed that sleep deprivation reduced PrPC and mGluR1 levels with higher effect in active state (21 hr). Sleep deprivation also caused accumulation of Aß peptides in rest period (13 hr), while laminin levels were not affected. In vitro binding assay showed that Aßo can compete with LN for PrPC binding. The influence of Aßo was also observed in neuritogenesis. LN alone promoted longer neurite outgrowth than non-treated cells in both Prnp+/+ and Prnp0/0 genotypes. Aßo alone did not show any effects, but when added together with LN, it attenuated the effects of LN only in Prnp+/+ cells. Altogether, our findings indicate that sleep deprivation regulates the availability of PrPC and Aß peptides, and based on our in vitro assays, these alterations induced by sleep deprivation can negatively affect LN-PrPC interaction, which is known to play roles in neuronal plasticity.

Components evaluation of a web-based personalized normative feedback intervention for alcohol use among college students: a pragmatic randomized controlled trial with a dismantling design.

AIMS: To evaluate the effects of the two main components of a personalized normative feedback (PNF) [normative feedback only (NFO); and consequences feedback only (CFO)] compared with the full intervention (PNF) in reducing alcohol use and consequences. DESIGN: Three-arm pragmatic randomized controlled trial with dismantling design and 1-, 3- and 6-month follow-ups. SETTING: Web-based among Brazilian college students. PARTICIPANTS: College students (aged 18-30 years) who reported alcohol use in the last 3 months (n = 5476). INTERVENTIONS: (1) Full PNF (a) drinking profile; (b) normative comparisons; (c) practical costs; (d) alcohol consequences; (e) strategies to decrease risks; (2) NFO components (a), (b) and (e); or (3) CFO components (c), (d) and (e). MEASUREMENTS: The primary outcome was change in Alcohol Use Disorders Identification Test (AUDIT) score; secondary outcomes were the number of alcohol consequences, drinking frequency and typical/maximum number of drinks. We used mixed models with multiple imputation and a pattern-mixture model to account for attrition. Subgroup analyses considered participant motivation to know more about their drinking (less motivated versus motivated). FINDINGS: Dismantled components reduced rather than increased AUDIT score compared to full PNF, with significant effects for NFO at 1 month [b = -0.23, 95% confidence interval (CI) = -0.46; -0.002] and for CFO at 3 months (b = -0.33, 95% CI = -0.62; -0.03). Compared with PNF, NFO reduced the number of alcohol consequences at 1 month (b = -0.16, 95% CI = -0.25; -0.06) and drinking frequency at 3 months (b = -0.42, 95% CI = -0.79; -0.05), but increased the number of typical drinks at 6 months (b = 0.38, 95% CI = 0.04; 0.72). CFO reduced drinking frequency at 3 months (b = -0.37, 95% CI = -0.73; -0.01). Attrition models confirmed all results, except for the NFO effect on typical drinks and drinking frequency. Subgroup analyses indicated superiority of dismantled components among the students less motivated in knowing more about their drinking. CONCLUSIONS: There was no evidence that either the normative or the consequences components of a web-based personalized normative feedback intervention to reduce alcohol use and its consequences contributed to intervention effects. There was some evidence of adverse effects of personalized normative feedback, and these results were driven by 20% of participants who were less motivated in knowing more about their drinking.

Effects of resistance exercise training and stretching on chronic insomnia

Objective: The aim of this study was to assess the effects of resistance exercise and stretching on sleep, mood, and quality of life in chronic insomnia patients. Methods: Three 4-month treatments included: resistance exercise (n=10), stretching (n=10), and control (n=8). Sleep was evaluated with polysomnography, actigraphy, and questionnaires. Mood and quality of life were assessed with the Profile of Mood States (POMS) and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), respectively. Results: There were no significant treatment differences between resistance exercise and stretching. However, compared with the control treatment, resistance exercise and stretching led to significantly greater improvements in Insomnia Severity Index scores (-10.5±2.3, -8.1±2.0 vs. 2.3±1.8, respectively), and actigraphic measures of sleep latency (-7.1±4.6, -5.2±1.9 vs. 2.2±2.1 min), wake after sleep onset (-9.3±2.8, -7.1±3.0 vs. 3.6±4.2 min), and sleep efficiency (4.4±1.8, 5.0±0.8 vs. -2.3±2%). Pittsburgh Sleep Quality Index (PSQI) global scores (-5.3±0.8, -3.9±1.5 vs. -0.1±0.8) and sleep duration (1.2±0.3, 1.6±0.6 vs. -0.1±0.2 h) also improved following both experimental treatments compared with control. PSQI-Sleep efficiency increased after resistance exercise compared with control (19.5±3.9 vs. 2.1±4.3%). No significant differences were observed in polysomnography or quality of life measures. Tension-anxiety was lower in the stretching group than the control group. Conclusion: Moderate-intensity resistance exercise and stretching led to similar improvements in objective and subjective sleep in patients with chronic insomnia. Clinical trial registration: NCT01571115

Effects of resistance exercise training and stretching on chronic insomnia.

OBJECTIVE: The aim of this study was to assess the effects of resistance exercise and stretching on sleep, mood, and quality of life in chronic insomnia patients. METHODS: Three 4-month treatments included: resistance exercise (n=10), stretching (n=10), and control (n=8). Sleep was evaluated with polysomnography, actigraphy, and questionnaires. Mood and quality of life were assessed with the Profile of Mood States (POMS) and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), respectively. RESULTS: There were no significant treatment differences between resistance exercise and stretching. However, compared with the control treatment, resistance exercise and stretching led to significantly greater improvements in Insomnia Severity Index scores (-10.5±2.3, -8.1±2.0 vs. 2.3±1.8, respectively), and actigraphic measures of sleep latency (-7.1±4.6, -5.2±1.9 vs. 2.2±2.1 min), wake after sleep onset (-9.3±2.8, -7.1±3.0 vs. 3.6±4.2 min), and sleep efficiency (4.4±1.8, 5.0±0.8 vs. -2.3±2%). Pittsburgh Sleep Quality Index (PSQI) global scores (-5.3±0.8, -3.9±1.5 vs. -0.1±0.8) and sleep duration (1.2±0.3, 1.6±0.6 vs. -0.1±0.2 h) also improved following both experimental treatments compared with control. PSQI-Sleep efficiency increased after resistance exercise compared with control (19.5±3.9 vs. 2.1±4.3%). No significant differences were observed in polysomnography or quality of life measures. Tension-anxiety was lower in the stretching group than the control group. CONCLUSION: Moderate-intensity resistance exercise and stretching led to similar improvements in objective and subjective sleep in patients with chronic insomnia. CLINICAL TRIAL REGISTRATION: NCT01571115.

Periodic limb movement in sleep and sickle cell disease: a neglected association?

High frequency of periodic limb movements in sleep (PLMS) has been described among children with sickle cell disease (SCD), but there is little information about PLMS among adults with SCD. We aim to determine the frequency of PLMS among adults with SCD and to identify possible associations with iron status and haemolytic parameters. We analysed polysomnography on 99 adults: 74 with sickle cell anaemia (HbSS), 19 with HbSC (double heterozygosis HbS and HbC) and 6 with HbS-beta thalassaemia. Laboratory data were collected close to the time of the polysomnography examination. The prevalence of PLMS > 5/h was 70% and of PLMS > 15/h 36%, in the total group of patients. No differences were observed regarding gender, use of hydroxyurea and iron parameters. Logistic regression showed an association between PLMS > 15/h and hemolytic parameters: absolute reticulocyte count (p = 0.03) and unconjugated bilirubin (p = 0.01). Our data suggest that PLMS may be associated with manifestations of greater severity in SCD.

Predictive Factors of One-Year Mortality in a Cohort of Patients Undergoing Urgent-Start Hemodialysis.

BACKGROUND: Chronic kidney disease (CKD) affects 10-15% of adult population worldwide. Incident patients on hemodialysis, mainly those on urgent-start dialysis at the emergency room, have a high mortality risk, which may reflect the absence of nephrology care. A lack of data exists regarding the influence of baseline factors on the mortality of these patients. The aim of this study was to evaluate the clinical and laboratory characteristics of this population and identify risk factors that contribute to their mortality. PATIENTS AND METHODS: We studied 424 patients who were admitted to our service between 01/2006 and 12/2012 and were followed for 1 year. We analyzed vascular access, risk factors linked to cardiovascular disease (CVD) and mineral and bone disease associated with CKD (CKD-MBD), and clinical events that occurred during the follow-up period. Factors that influenced patient survival were evaluated by Cox regression analysis. RESULTS: The patient mean age was 50 ± 18 years, and 58.7% of them were male. Hypertension was the main cause of primary CKD (31.8%). Major risk factors were smoking (19.6%), dyslipidemia (48.8%), and CVD (41%). Upon admission, most patients had no vascular access for hemodialysis (89.4%). Biochemical results showed that most patients were anemic with high C-reactive protein levels, hypocalcemia, hyperphosphatemia, elevated parathyroid hormone and decreased 25-hydroxy vitamin D. At the end of one year, 60 patients died (14.1%). These patients were significantly older, had a lower percentage of arteriovenous fistula in one year, and low levels of 25-hydroxy vitamin D. CONCLUSIONS: The combined evaluation of clinical and biochemical parameters and risk factors revealed that the mortality in urgent-start dialysis is associated with older age and low levels of vitamin D deficiency. A lack of a permanent hemodialysis access after one year was also a risk factor for mortality in this population.

Haloperidol increases false recognition memory of thematically related pictures in healthy volunteers.

Dopamine can modulate long-term episodic memory. Its potential role on the generation of false memories, however, is less well known. In a randomized, double-blind, placebo-controlled experiment, 24 young healthy volunteers ingested a 4-mg oral dose of haloperidol, a dopamine D2 -receptor antagonist, or placebo, before taking part in a recognition memory task. Haloperidol was active during both study and test phases of the experiment. Participants in the haloperidol group produced more false recognition responses than those in the placebo group, despite similar levels of correct recognition. These findings show that dopamine blockade in healthy volunteers can specifically increase false recognition memory.

Effects of Sulpiride on True and False Memories of Thematically Related Pictures and Associated Words in Healthy Volunteers.

Episodic memory, working memory, emotional memory, and attention are subject to dopaminergic modulation. However, the potential role of dopamine on the generation of false memories is unknown. This study defined the role of the dopamine D2 receptor on true and false recognition memories. Twenty-four young, healthy volunteers ingested a single dose of placebo or 400 mg oral sulpiride, a dopamine D2-receptor antagonist, just before starting the recognition memory task in a randomized, double-blind, and placebo-controlled trial. The sulpiride group presented more false recognitions during visual and verbal processing than the placebo group, although both groups had the same indices of true memory. These findings demonstrate that dopamine D2 receptors blockade in healthy volunteers can specifically increase the rate of false recognitions. The findings fit well the two-process view of causes of false memories, the activation/monitoring failures model.

Functional versus Nonfunctional Rehabilitation in Chronic Ischemic Stroke: Evidences from a Randomized Functional MRI Study.

Motor rehabilitation of stroke survivors may include functional and/or nonfunctional strategy. The present study aimed to compare the effect of these two rehabilitation strategies by means of clinical scales and functional Magnetic Resonance Imaging (fMRI). Twelve hemiparetic chronic stroke patients were selected. Patients were randomly assigned a nonfunctional (NFS) or functional (FS) rehabilitation scheme. Clinical scales (Fugl-Meyer, ARA test, and modified Barthel) and fMRI were applied at four moments: before rehabilitation (P1) and immediately after (P2), 1 month after (P3), and three months after (P4) the end of rehabilitation. The NFS group improved significantly and exclusively their Fugl-Meyer scores at P2, P3, and P4, when compared to P1. On the other hand, the FS group increased significantly in Fugl-Meyer at P2, when compared to P1, and also in their ARA and Barthel scores. fMRI inspection at the individual level revealed that both rehabilitation schemes most often led to decreased activation sparseness, decreased activity of contralesional M1, increased asymmetry of M1 activity to the ipsilesional side, decreased perilesional activity, and decreased SMA activity. Increased M1 asymmetry with rehabilitation was also confirmed by Lateralization Indexes. Our clinical analysis revealed subtle differences between FS and NFS.

Omega-3 Levels and Nicotine Dependence: A Cross-Sectional Study and Clinical Trial.

BACKGROUND: High oxidative stress, which is caused by smoking, can alter omega-3 fatty acid concentrations. Since omega-3 fatty acids play a role in dopaminergic neurotransmission related to dependence, it is important to understand their effects on nicotine dependence. METHODS: This research comprised 2 studies. The first one consisted of a cross-sectional evaluation, in which the levels of the most important omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were compared between smokers and non-smokers in a sample of 171 individuals; of them, 120 were smokers and 51 were non-smokers. The other study was a clinical, double-blind, randomized, placebo controlled, in which 63 smokers received daily treatment with capsules of fish oil (a source of omega-3/3 g/day) or mineral oil (used as placebo, also 3 g/day), taken 3 times a day for 90 days. Each fish oil capsules contained approximately 210.99 mg EPA and 129.84 mg of DHA. The outcome was evaluated by means of psychometric and biological measures as well as self-reports of tobacco use. The evaluations were carried out at the beginning of treatment and once a month thereafter (total of 4 times). OUTCOMES: The omega-3 fatty acid lipid profile showed that smokers present lower concentrations of DHA. After treatment, the omega-3 group showed a significant reduction in their levels of dependence. INTERPRETATION: Smokers showed lower peripheral levels of omega-3, and treatment with the most important omega-3 fatty acids brought about a reduction in nicotine dependence.

Motivational and evolutionary aspects of a physical exercise training program: a longitudinal study.

Several studies have indicated that motivational level and prior expectations influence one's commitment to physical activity. Moreover, these aspects are not properly described in terms of proximal (SDT, Self Determination Theory) and distal (evolutionary) explanations in the literature. This paper aims to verify if level of motivation (BREQ-2, Behavioral Regulation in Exercise Questionnaire-2) and expectations regarding regular physical exercise (IMPRAF-54) before starting a 1-year exercise program could determine likelihood of completion. Ninety-four volunteers (53 women) included a completed protocol group (CPG; n = 21) and drop-out group (n = 73). The IMPRAF-54 scale was used to assess six different expectations associated with physical activity, and the BREQ-2 inventory was used to assess the level of motivation in five steps (from amotivation to intrinsic motivation). Both questionnaires were assessed before starting a regular exercise program. The CPG group presented higher sociability and lower pleasure scores according to IMPRAF-54 domains. A logistic regression analysis showed that a one-point increment on sociability score increased the chance of completing the program by 10%, and the same one-point increment on pleasure score reduced the chance of completing the protocol by 16%. ROC curves were also calculated to establish IMPRAF-54 cutoffs for adherence (Sociability - 18.5 points - 81% sensibility/50% specificity) and dropout (Pleasure - 25.5 points - 86% sensibility/20% specificity) of the exercise protocol. Our results indicate that an expectation of social interaction was a positive factor in predicting adherence to exercise. Grounded in SDT and its innate needs (competence, autonomy, relatedness), physical exercise is not an end; it is a means to achieve autonomy and self-cohesion. The association of physical activity with social practices, as occurs in hunter-gathering groups, can engage people to be physically active and can provide better results in adherence exercise programs for the general population.

Impact of OSA on cardiovascular events after coronary artery bypass surgery.

BACKGROUND: The impact of OSA on new cardiovascular events in patients undergoing coronary artery bypass graft (CABG) surgery is poorly explored. METHODS: Consecutive patients referred for CABG underwent clinical evaluation and standard polysomnography in the preoperative period. CABG surgery data, including percentage of off-pump and on-pump CABG, number of grafts, and intraoperative complications, were collected. The primary end point was major adverse cardiac or cerebrovascular events (MACCEs) (combined events of all-cause death, myocardial infarction, repeated revascularization, and cerebrovascular events). Secondary end points included individual MACCEs, typical angina, and arrhythmias. Patients were evaluated at 30 days (short-term) and up to 6.1 years (long term) after CABG. RESULTS: We studied 67 patients (50 men; mean age, 58 ± 8 years; mean BMI, 28.5 ± 4.1 kg/m2). OSA (apnea-hypopnea index ≥ 15 events/h) was present in 56% of the population. The patients were followed for a mean of 4.5 years (range, 3.2-6.1 years). No differences were observed in the short-term follow-up. In contrast, MACCE (35% vs 16%, P = .02), new revascularization (19% vs 0%, P = .01), episodes of typical angina (30% vs 7%, P = .02), and atrial fibrillation (22% vs 0%, P = .0068) were more common in patients with than without OSA in the long-term follow-up. OSA was an independent factor associated with the occurrence of MACCE, repeated revascularization, typical angina, and atrial fibrillation in the multivariate analysis. CONCLUSIONS: OSA is independently associated with a higher rate of long-term cardiovascular events after CABG and may have prognostic and economic significance in CABG surgery.

Evaluation and validation of a method for determining platelet catecholamine in patients with obstructive sleep apnea and arterial hypertension.

BACKGROUND: Measurements of plasma and urinary catecholamine are susceptible to confounding factors that influence the results, complicating the interpretation of sympathetic nervous system (SNS) activity in the Obstructive sleep apnea (OSA) and arterial hypertension (HYP) conditions. OBJECTIVE: In this study, we validated a test for platelet catecholamine and compared the catecholamine levels (adrenaline and noradrenaline) in urine, plasma and platelets in patients with OSA and HYP compared with controls. METHODS: In the validation, 30 healthy, nonsmoking volunteers who were not currently undergoing treatment or medication were selected as the control group. One hundred fifty-four individuals (114 OSA, 40 non-OSA) were consecutively selected from the outpatient clinic of the Sleep Institute and underwent clinical, polysomnographic and laboratory evaluation, including the urinary, plasma and platelet levels of adrenaline (AD) and noradrenaline (NA). Patients were then allocated to groups according to the presence of OSA and/or hypertension. RESULTS: A logistic regression model, controlled for age and BMI, showed that urinary AD and urinary NA were risk factors in the OSA+HYP group and the HYP group; however, the model showed higher levels of platelet NA for OSA without HYP. After 1 year of CPAP (continuous upper airway pressure) treatment, patients (n = 9) presented lower levels of urinary NA (p = 0.04) and platelet NA (p = 0.05). CONCLUSION: Urinary NA and AD levels were significantly associated with the condition of hypertension with and without OSA, whereas platelet NA with OSA without comorbidity. These findings suggest that platelet catecholamine levels might reflect nocturnal sympathetic activation in OSA patients without hypertension.

Six-minute walk test in healthy children: is the leg length important?

RATIONALE: Measures as height, age, and weight influence the six-minute walk test (6MWT). It was shown that children's true leg length (TLL) influence the 6MWT distance but so far it has never been evaluated how much this variable could predict the distance walked related to height. Our hypothesis is that there should not have any significant difference between models including height or TLL. OBJECTIVE: To establish and to compare the predicted walked distance of healthy children in the 6MWT by two distinct models, one including TLL and other including height. METHODS: Observational cross sectional study. A total of 161 healthy children (84 girls, 52.2%), 6-13 years old from three local primary and secondary schools. Two 6MWT were performed following ATS guidelines. Weight, height, and TLL were measured. The longer walked distance was selected for statistical analysis. RESULTS: Anthropometric data were similar for both genders into each group of age. Mean (±SD) walked distances in whole group were: boys 704.4 m (77.7); girls 681.6 m (67.9; P = 0.049). In the univariate regression to predict the distance walked, the adjusted coefficients to TLL and height were in boys: 0.46 and 0.39; and in girls: 0.35 and 0.29, respectively. After adjusting for age and weight, the residuals of the two equations were not significantly different (P = 0.998). CONCLUSION: The model including TLL to predict the walked distance by healthy children explained more of the variation on the walked distance in the 6MWT than the model using the height but without significant difference between the models.