Mitochondrial transplantation ameliorates hippocampal damage following status epilepticus

Background:Hippocampal damage caused by status epilepticus(SE)can bring about cognitive decline and emotional disorders,which are common clinical comorbidities in patients with epilepsy.It is therefore imperative to develop a novel therapeutic strat-egy for protecting hippocampal damage after SE.Mitochondrial dysfunction is one of contributing factors in epilepsy.Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria,we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.Methods:Pilocarpine was used to induced SE in mice.SE-generated cognitive de-cline and emotional disorders were determined using novel object recognition,the tail suspension test,and the open field test.SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes.The metabolites underlying mitochondrial transplantation were determined using metabonomics.Results:The results showed that peripheral administration of isolated mitochon-dria could improve cognitive deficits and depressive and anxiety-like behaviors.Exogenous mitochondria blunted the production of reactive oxygen species,pro-liferation of microglia and astrocytes,and loss of neurons in the hippocampus.The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism.Among potential affected metabolites,mitochondrial transplantation decreased levels of sphingolipid(d18:1/18:0)and methylmalonic acid,and elevated levels of D-fructose-1,6-bisphosphate.Conclusion:To the best of our knowledge,these findings provide the first direct ex-perimental evidence that artificial mitochondrial transplantation is capable of amelio-rating hippocampal damage following SE.These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiat-ric and cognitive disorders.

Improving wellbeing of community-dwelling people with mild cognitive impairment: the SENIOR (SystEm of Nudge theory based ICT applications for OldeR citizens) project

Population aging with longer life expectancy represents one of the most relevant challenges of the next future,also because of a significant proportion of older adult people may present with dementia.Motivating senior citizens with mild cognitive impairment to maintain their independence and functional abilities,improve health status and quality of life as well as social interactions,constitutes the main target of preventive medicine.According to a nudge theoretical approach,the SENIOR(SystEm of Nudge theory based ICT applications for OldeR citizens)project–developed thanks to the collaboration among Catholic University of the Sacred Heart,Bicocca University and IRCCS Auxiologico Institute in Milan(Italy)–has been designed to adopt an advanced information and communication technology coaching system able to collect and integrate physiological,psychological and behavioral data,with the final aim of interacting with community-dwelling elderly people suffering from mild cognitive impairment and of providing them personalized feedback on lifestyle management.The SENIOR project proposes to use a smart-watch app for alerting family doctors,sharing information with family members in specific cases and monitoring patients at higher risk in hospital Units,in order to ameliorate health of senior citizens with mild cognitive impairment.

初发症状性脑梗死患者接受静脉重组组织型纤溶酶原激活剂治疗后的认知和功能预后

Objective: To examine whether intravenous recombinant tissue plasminogen activator (rt-PA) treatment given in the acute phase of ischaemic stroke has a favourable effect on cognitive and functional outcome at six months post-stroke. Methods: The present study included 92 patients with a first-ever symptomatic infarct, of whom 25 (27 %) were subjected to rt-PA treatment in the first three hours post-stroke. Multivariate logistic regression analyses adjusted for stroke severity, education, age, and sex were performed to examine whether rt-PA treatment influenced cognitive outcome (assessed with a neuropsychological examination covering 7 cognitive domains), basic ADL independence (modified Barthel Index ≥19), and instrumental ADL independence (Frenchay Activities Index ≥15) after six months. Results: The adjusted odds ratio for intact cognition was 1.0 (95%CI 0.2 to 4.3), that for basic ADL outcome 13.5 (95%CI 1.4 to 129.4) and for instrumental ADL 7.1 (95%CI 1.2 to 42.2). Conclusion: Our findings suggest that rt-PA treatment is associated with a favourable basic and instrumental ADL outcome, but not with a beneficial cognitive outcome after 6 months.

Apoptosis and autophagy control cell proliferation in the dentate gyrus following hippocampal lesion

Brain injuries often result in the promotion of cell proliferation in the hippocampal dentate gyrus（DG）,but the number of newborn cells declines with time.However,the cause of this decline remains poorly understood.Elucidation of the fate of these newborn cells will further the understanding of the pathological process and treatment of brain injury.In the present study,the number of newborn cells was quantitatively analyzed using an unbiased stereological method following hippocampal lesion by kainic acid,in combination with detection of apoptosis and autophagy.Results revealed that hippocampal lesion resulted in a significantly increased number of 5-bromo-2-deoxyuridine（BrdU）-positive cells in the DG,which subsequently decreased with time.BrdU/cleaved caspase-3 double-labeled cells were detected in the granular cell layer and hilus of DG.However,expressions of LC3-11,Beclin 1,and p53 were upregulated,and pro-caspase-3 and Bcl-2 were downregulated.Results indicated that hippocampal lesion in adult rats resulted in significant cell proliferation in the DG,which subsequently reduced with time.In addition,results suggested that apoptosis and autophagic processes could regulate cell proliferation in the DG following hippocampal lesion.

Breast Cancer Paradox: High Curability versus High Mortality from a Gender Perspective

Despite being considered a potentially curable disease, breast cancer is the most frequent cause of cancer death in women worldwide, establishing the following paradox: high curability versus high mortality. Among the conditions conducive to this situation, such as difficult access to diagnosis and treatment and social support by the State, there is the need to discuss the impact of women’s caregiving, the backbone of the female gender role, on self-care in health. Gender has a powerful effect on determining health status: it may limit different rates of exposure to certain risks, different patterns in the quest for treatment or differential impacts of the social and economic determinants of health. The study shows the results of a qualitative methodology with nine women aged 48 to 74 years with varying levels of schooling and socioeconomic status, who had breast cancer at some stage of adult life and who regularly attend a nongovernmental organization (NGO) to support women with breast cancer, in the city of Niterói (Rio de Janeiro, Brazil). The participants’ discourses evidenced the idea of the primacy of the caregiving, the idealized image of the warrior woman and their self-neglect and State’s care as elements of the potential impact on the choices of these women concerning self-care, and consequently in their experiences of illness.

The Relationship of Effortful Control to Academic Achievement via Children’s Learning-Related Behaviors

Effortful control (EC) is a temperamental self-regulatory capacity, defined as the efficiency of executive attention [1], which is related to individual differences in self-regulation. Although effortful control covers some dispositional self-regulatory abilities important to cope with social demands of successful adaptation to school, such as attention regulation, individual differences in EC have recently been associated with school functioning through academic achievement including the efficient use of learning-related behaviors, which have been found to be a necessary precursor of learning and they refer to a set of children’s behaviors that involve organizational skills and appropriate habits of study. Therefore, the aim of this study is to review the literature on EC’s relationship to academic achievement via learning-related behaviors, which reflect the use of metacognitive control processes in kindergarten and elementary school students. The findings indicate that EC affects academic achievement through the facilitation of the efficient use of metacognitive control processes.

Validation of the Chinese Version of the Affective Exercise Experiences Questionnaire (AFFEXX-C)

Despite the well-established benefits of regular physical activity(PA)on health,a large proportion of the world population does not achieve the recommended level of regular PA.Although affective experiences toward PA may play a key role to foster a sustained engagement in PA,they have been largely overlooked and crudely measured in the existing studies.To address this shortcoming,the Affective Exercise Experiences(AFFEXX)questionnaire has been developed to measure such experiences.Specifically,this questionnaire was developped to assess the following three domains:antecedent appraisals(e.g.,liking vs.disliking exercise in groups),core affective exercise experiences(i.e.,pleasure vs.displeasure,energy vs.tiredness,and calmness vs.tension),and exercise motivation(i.e.,attraction vs.antipathy toward exercise).The current study aimed to validate a Chinese version of the AFFEXX questionnaire(AFFEXX-C).In study 1,722 Chinese college students provided data for analyses of factorial,convergent,discriminant,criterion validity,and test-retest reliability of the AFFEXX-C.In addition,1,300 college students were recruited in study 2 to further validate its structural model.Results showed that the AFFEXX-C demonstrates a goodfit and reliability.Additionally,results further supported the hypothesized model based on previous research:antecedent appraisals predicted core affective exercise experiences,which in turn predicted attraction-antipathy toward physical exercise.The AFFEXX-C was found to be a reliable and valid measure of affective exercise experiences in a population of Chinese college students.

Statistical issues and approaches in endophenotype research

The endophenotype concept was initially proposed to enhance the power of genetic studies of complex disorders. It is closely related to the genetic component in a liability-threshold model; a perfect endophenotype should have a correlation of 1 with the genetic component of the liability to disease. In reality, a putative endophenotype is unlikely to be a perfect representation of the genetic component of disease liability. The magnitude of the correlation between a putative endophenotype and the genetic component of disease liability can be estimated by fitting multivariate genetic models to twin data. A number of statistical methods have been developed for incorporating endophenotypes in genetic linkage and association analyses with the aim of improving statistical power. The most recent of such methods can handle multiple endophenotypes simultaneously for the greatest increase in power. In addition to increasing statistical power, endophenotype research plays an important role in helping to understand the mechanisms which connect the associated genetic variants with disease occurrence. Novel statistical approaches may be required for the analysis of the complex relationships between endophenotypes at different levels and how they converge to cause the occurrence of disease.

Treatment of depression using sleep electroencephalogram modulated repetitive transcranial magnetic stimulation

Background As a treatment of depression, the efficacy of conventional repetitive transcranial magnetic stimulation （rTMS） is limited, and symptoms recurrence is easy to occur after the treatment. This study aimed to examine the efficacy and safety of sleep electroencephalogram modulated repetitive rTMS （SEM-rTMS） in the treatment of depression. Methods After 7 days without psychoactive medication, 164 patients with clinically defined depression were randomly divided into 3 groups： SEM-rTMS group （n=-57）, conventional rTMS （C-rTMS, n=55） group and sham-rTMS group （n=-52）. Every patient was treated with the corresponding method for 30 minutes everyday for 10 days. Before and after scores on the 24-item Hamilton rating scale for depression （HAMD-24） and the clinical outcome on the 10th day of therapy for all subjects were analyzed. Results Twenty-two cases in the SEM-rTMS group obtained improved mood as compared to 6 in the C-rTMS group and 2 in the sham-rTMS group （X2=15.89, P=0.0004）. After completion of the rTMS phase of the protocol, a （51±5）% reduction of HAMD-24 scores from the baseline in the SEM-rTMS group was found compared with a （34±4）% in the C-rTMS group （q=26.09, P=-0.001） and a （14±3）% in sham-rTMS group （q=57.53, P=0.000）. The 88% total effective rate in the SEM-rTMS group was significantly higher than 68% in the C-rTMS group and 20% in the sham-rTMS group （χ2=12.01, P=0.0025）. No significant side effects were noted. Conclusion SEM-rTMS is an effective and safe way for treating depression with repetitive transcranial magnetic stimulation （ChiCTR-TRC-00000438）.