The role of Nox2-derived ROS in the development of cognitive impairment after sepsis

BACKGROUND: Sepsis- associated encephalopathy (SAE) is an early and common feature of severe infections. Oxidative stress is one of the mechanisms associated with the pathophysiology of SAE. The goal of this study was to investigate the involvement of NADPH oxidase in neuroinflammation and in the long-term cognitive impairment of sepsis survivors. METHODS: Sepsis was induced in WT and gp91phox knockout mice (gp91phox-/-) by cecal ligation and puncture (CLP) to induce fecal peritonitis. We measured oxidative stress, Nox2 and Nox4 gene expression and neuroinflammation in the hippocampus at six hours, twenty-four hours and five days post-sepsis. Mice were also treated with apocynin, a NADPH oxidase inhibitor. Behavioral outcomes were evaluated 15 days after sepsis with the inhibitory avoidance test and the Morris water maze in control and apocynin-treated WT mice. RESULTS: Acute oxidative damage to the hippocampus was identified by increased 4-HNE expression in parallel with an increase in Nox2 gene expression after sepsis. Pharmacological inhibition of Nox2 with apocynin completely inhibited hippocampal oxidative stress in septic animals. Pharmacologic inhibition or the absence of Nox2 in gp91phox-/- mice prevented glial cell activation, one of the central mechanisms associated with SAE. Finally, treatment with apocynin and inhibition of hippocampal oxidative stress in the acute phase of sepsis prevented the development of long-term cognitive impairment. CONCLUSIONS: Our results demonstrate that Nox2 is the main source of reactive oxygen species (ROS) involved in the oxidative damage to the hippocampus in SAE and that Nox2-derived ROS are determining factors for cognitive impairments after sepsis. These findings highlight the importance of Nox2-derived ROS as a central mechanism in the development of neuroinflammation associated with SAE.

Effects of repetitive transcranial magnetic stimulation on clinical, social, and cognitive performance in postpartum depression

Background: This randomized, placebo-controlled, double-blind pilot study evaluated the impact of repetitive transcranial magnetic stimulation (rTMS) on clinical, cognitive, and social performance in women suffering with postpartum depression. Methods: Fourteen patients were randomized to receive 20 sessions of sham rTMS or active 5 Hz rTMS over the left dorsolateral prefrontal cortex. Psychiatric clinical scales and a neuropsychological battery were applied at baseline (pretreatment), week 4 (end of treatment), and week 6 (follow-up, posttreatment week 2). Results: The active rTMS group showed significant improvement 2 weeks after the end of rTMS treatment (week 6) in Hamilton Depression Rating Scale (P = 0.020), Global Assessment Scale (P = 0.037), Clinical Global Impression (P = 0.047), and Social Adjustment Scale-Self Report-Work at Home (P = 0.020). Conclusion: This study suggests that rTMS has the potential to improve the clinical condition in postpartum depression, while producing marginal gains in social and cognitive function.

Vascular dementia: Different forms of vessel disorders contribute to the development of dementia in the elderly brain

The diagnosis of vascular dementia (VaD) describes a group of various vessel disorders with different types of vascular lesions that finally contribute to the development of dementia. Most common forms of VaD in the elderly brain are subcortical vascular encephalopathy, strategic infarct dementia, and the multi infarct encephalopathy. Hereditary forms of VaD are rare. Most common is the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Sporadic forms of VaD are caused by degenerative vessel disorders such as atherosclerosis, small vessel disease (SVD) including small vessel arteriosclerosis, arteriolosclerosis, and lipohyalinosis, and cerebral amyloid angiopathy (CAA). Less frequently inflammatory vessel disorders and tumor-associated vessel lesions (e. g. angiocentric T-cell or angiotropic large cell lymphoma) can cause symptoms of dementia. Here, we review and discuss the impact of vessel disorders to distinct vascular brain tissue lesions and to the development of dementia in elderly individuals. The impact of coexisting neurodegenerative pathology in the elderly brain to VaD as well as the correlation between SVD and CAA expansion in the brain parenchyma with that of Alzheimer's disease (AD)-related pathology is highlighted. We conclude that "pure" VaD is rare and most frequently caused by infarctions. However, there is a significant contribution of vascular lesions and vessel pathology to the development of dementia that may go beyond tissue damage due to vascular lesions. Insufficient blood blow and alterations of the perivascular drainage mechanisms of the brain may also lead to a reduced protein clearance from extracellular space and subsequent increase of proteins in the brain parenchyma, such as the amyloid beta-protein, and foster, thereby, the development of AD-related neurodegeneration. As such, it seems to be important for clinical practice to consider treatment of potentially coexisting AD pathology in cognitively impaired patients with vascular lesions. (C) 2012 Elsevier Inc. All rights reserved.

Gray Matter Volumes in Obsessive-Compulsive Disorder Before and After Fluoxetine or Cognitive-Behavior Therapy: A Randomized Clinical Trial

Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n = 38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n = 36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n = 26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n = 13), whereas no significant GM volume changes were observed in CBT-treated patients (n = 13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action. Neuropsychopharmacology (2012) 37, 734-745; doi: 10.1038/npp.2011.250; published online 26 October 2011

Development and validation of an instrument to assess movement quality of the basketball free throw shooting

When a physical activity professional is teaching a motor skill, he evaluates the movement's learner and considers which interventions could be done at the moment. However, many times the instructor does not have such resources which could help him/her to evaluate the learner movement. The skill acquisition process could be facilitated if instructors could have an instrument that identifies errors, prioritizing information to be given to the learner. Considering that the specialized literature presents a lack of information about such tool, the purpose of this study was to develop, and to determine the objectivity and reliability of an instrument to assess the movement quality of the basketball free throw shooting. The checklist was developed and evaluated by basketball experts. Additionally, the checklist was used to assess 10 trials (edited video) from four individuals in different learning stages. Data were organized by the critical error and the error sum appointed by the experts in two different occasions (one week interval). Contrasting both evaluations, and also, contrasting different experts assessments, in sum and critical error, it was observed an average error of 16.9%. It was concluded that the checklist to assess the basketball free throw is reliable, and could help instructors to make a qualitative analysis. Moreover, the checklist may allow instructors to make assumptions on the motor learning process.

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders

Rationale Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. Objectives We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Methods Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. Results A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. Conclusions The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

A structural model of emotions of cognitive dissonances

Cognitive dissonance is the stress that comes from holding two conflicting thoughts simultaneously in the mind, usually arising when people are asked to choose between two detrimental or two beneficial options. In view of the well-established role of emotions in decision making, here we investigate whether the conventional structural models used to represent the relationships among basic emotions, such as the Circumplex model of affect, can describe the emotions of cognitive dissonance as well. We presented a questionnaire to 34 anonymous participants, where each question described a decision to be made among two conflicting motivations and asked the participants to rate analogically the pleasantness and the intensity of the experienced emotion. We found that the results were compatible with the predictions of the Circumplex model for basic emotions. (C) 2012 Elsevier Ltd. All rights reserved.

The relationship between social support and functional capacity in elderly persons with cognitive alterations

The objective of this study was to identify the relationship between social support and the functional capacity of elderly persons with cognitive alterations. It is a descriptive, cross-sectional and quantitative study. The subjects were 101 elderly persons registered in Family Health Centers whose performance in the Mini-Exam for Mental Status was below a certain specified level in a previous study. The Medical Outcomes Study questionnaire, Katz Index and Pfeffer Questionnaire were applied. The dimensions of material, affective, emotional, informational and positive social interaction support resulted in an average final score of 74.32 points, indicating a better level of material and affective support in relation to the other dimensions of support. There was a statistically significant correlation between emotional support and the Katz Index. Knowledge about this relationship favors the development of a nursing care pathway for the elderly which is capable of maintaining their functional capacity and ensuring satisfactory social relations.

Determinants of cognitive performance among community dwelling older adults in an impoverished sub-district of Sao Paulo in Brazil

Determinants of cognitive performance in old age have received limited attention in Latin America. We investigated the association of socio-demographic and health-related variables with cognitive performance in a sample of older adults with limited educational experience living in a poor subdistrict of the city of Sao Paulo. This was a cross-sectional population-based study which included a sample of 384 seniors 65 years and older. Cognition was assessed by the Mini-Mental State Examination (MMSE) and the Brief Cognitive Screening Battery (BCSB) (episodic memory test with 10 pictures, verbal fluency (VF), Clock Drawing Test (CDT)). Results indicated that age, sex, schooling, depressive symptoms, and systolic blood pressure (SBP) level had a significant impact on the cognitive performance of the sample. Therefore, pharmacological and psychosocial interventions with a focus on improving mood and controlling hypertension may have beneficial effects on cognition among seniors with similar socio-demographic characteristics. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of a video on developing skills in undergraduate nursing students for the management of totally implantable central venous access ports

Background: Handling Totally Implantable Access Ports (TIAP) is a nursing procedure that requires skill and knowledge to avoid adverse events. No studies addressing this procedure with undergraduate students were identified prior to this study. Communication technologies, such as videos, have been increasingly adopted in the teaching of nursing and have contributed to the acquisition of competencies for clinical performance. Objective: To evaluate the effect of a video on the puncture and heparinization of TIAP in the development of cognitive and technical competencies of undergraduate nursing students. Method: Quasi-experimental study with a pretest-posttest design. Results: 24 individuals participated in the study. Anxiety scores were kept at levels 1 and 2 in the pretest and posttest. In relation to cognitive knowledge concerning the procedure, the proportion of correct answers in the pretest was 0.14 (SD=0.12) and 0.90 in the posttest (SD=0.05). After watching the video, the average score obtained by the participants in the mock session was 27.20. Conclusion: The use of an educational video with a simulation of puncture and heparinization of TIAP proved to be a strategy that increased both cognitive and technical knowledge. This strategy is viable in the teaching-learning process and is useful as a support tool for professors and for the development of undergraduate nursing students. (C) 2011 Elsevier Ltd. All rights reserved.

Motor learning, retention and transfer after virtual-reality-based training in Parkinson's disease - effect of motor and cognitive demands of games: a longitudinal, controlled clinical study

Objectives To evaluate the learning, retention and transfer of performance improvements after Nintendo Wii Fit (TM) training in patients with Parkinson's disease and healthy elderly people. Design Longitudinal, controlled clinical study. Participants Sixteen patients with early-stage Parkinson's disease and 11 healthy elderly people. Interventions Warm-up exercises and Wii Fit training that involved training motor (shifts centre of gravity and step alternation) and cognitive skills. A follow-up evaluative Wii Fit session was held 60 days after the end of training. Participants performed a functional reach test before and after training as a measure of learning transfer. Main outcome measures Learning and retention were determined based on the scores of 10 Wii Fit games over eight sessions. Transfer of learning was assessed after training using the functional reach test. Results Patients with Parkinson's disease showed no deficit in learning or retention on seven of the 10 games, despite showing poorer performance on five games compared with the healthy elderly group. Patients with Parkinson's disease showed marked learning deficits on three other games, independent of poorer initial performance. This deficit appears to be associated with cognitive demands of the games which require decision-making, response inhibition, divided attention and working memory. Finally, patients with Parkinson's disease were able to transfer motor ability trained on the games to a similar untrained task. Conclusions The ability of patients with Parkinson's disease to learn, retain and transfer performance improvements after training on the Nintendo Wii Fit depends largely on the demands, particularly cognitive demands, of the games involved, reiterating the importance of game selection for rehabilitation purposes. (C) 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Development of an integrative cessation program for co-smokers of cigarettes and cannabis: demand analysis, program description, and acceptability

Abstract Background Tobacco and cannabis use are strongly interrelated, but current national and international cessation programs typically focus on one substance, and address the other substance either only marginally or not at all. This study aimed to identify the demand for, and describe the development and content of, the first integrative group cessation program for co-smokers of cigarettes and cannabis. Methods First, a preliminary study using expert interviews, user focus groups with (ex-)smokers, and an online survey was conducted to investigate the demand for, and potential content of, an integrative smoking cessation program (ISCP) for tobacco and cannabis co-smokers. This study revealed that both experts and co-smokers considered an ISCP to be useful but expected only modest levels of readiness for participation.Based on the findings of the preliminary study, an interdisciplinary expert team developed a course concept and a recruitment strategy. The developed group cessation program is based on current treatment techniques (such as motivational interviewing, cognitive behavioural therapy, and self-control training) and structured into six course sessions.The program was evaluated regarding its acceptability among participants and course instructors. Results Both the participants and course instructors evaluated the course positively. Participants and instructors especially appreciated the group discussions and the modules that were aimed at developing personal strategies that could be applied during simultaneous cessation of tobacco and cannabis, such as dealing with craving, withdrawal, and high-risk situations. Conclusions There is a clear demand for a double cessation program for co-users of cigarettes and cannabis, and the first group cessation program tailored for these users has been developed and evaluated for acceptability. In the near future, the feasibility of the program will be evaluated. Trial registration Current Controlled Trials ISRCTN15248397