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International audience; Background: We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4).Methods: Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School.Results: Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers.Conclusion: High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.

International audience; BACKGROUND : Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI).METHODS : Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment.RESULTS : The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01).CONCLUSION : Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.

Flowcytometric analysis on T-cell subpopulations in the blood and cerebrospinal fluid (CSF) of 10 children with mumps meningitis (MM) revealed that the proportion of lymphocytes which bore the gamma delta T-cell receptor for antigen was significantly higher in CSF than in autologous and heterologous blood samples. gamma delta T-cell values in CSF of MM patients were also significantly higher than those calculated in CSF specimens from nine children with non-inflammatory neurological disorders. Whether and how the expanded CSF gamma delta T-lymphocyte subset, either CD8+ or double-negative (CD4-/CD8-), contributes to the eradication of mumps virus infection from the central nervous system represents a central focus of our ongoing research.

Although the relative and absolute numbers of CD3+ cells (T lymphocytes) were similar in eight children with acquired Toxoplasma gondii infection and 10 uninfected age- and sex-matched healthy controls, the proportion of cells bearing the gamma delta T-cell receptor was significantly higher in the subjects with acute toxoplasmosis. The great majority of gamma delta T cells from the infected patients expressed covalently bound gamma delta chains on their surface, i.e. were BB3+ lymphocytes. Since the gamma delta T-cell subsets exert both restricted and unrestricted major histocompatibility complex cytotoxicity, further research is needed to elucidate the role of gamma delta T cells in the control of this coccidian protozoan infection.

Our laboratories previously reported that the proportion of lymphocytes bearing the gamma/delta T-cell receptor (TcR) is twofold greater in human milk lymphocyte suspensions than in autologous and heterologous blood samples. The present investigation shows that gamma/delta colostral T cells preferentially express non-covalently bound gamma/delta chains, whereas only a few display the disulphide-linked form of the TcR. This contrasts with the picture in the blood, where the distribution of these two nonoverlapping subpopulations is proportionally inverse. These findings are further evidence that the colonization of the mammary gland during lactation by immune system cells is the result of a selective homing process.

Plasma cell generation in pokeweed mitogen-pulsed lymphocyte cultures was markedly suppressed when the experiments were carried out by adding cell-depleted cerebrospinal fluid (CSF) from 5 acute aseptic meningitis or meningoencephalitis children known to have an overexpanded cell population with the suppressor-cytotoxic T-cell surface phenotype in their CSF. In contrast, B-cell terminal differentiation was not affected by the addition of CSF from 5 control children with non-neurological diseases, thereby indicating that CSF from central nervous system virus-infected children contains soluble factors which are themselves capable of exerting regulatory influences on immunocompetent cells.

Background Doll therapy is a non-pharmacological intervention for people with dementia aimed to reduce distressing behaviours. Reliable results on the efficacy of Doll therapy for people with dementia are needed. The concept of attachment theorised by Bowlby has been proposed to explain the Doll therapy process, but it has not been proven to influence the response to doll presentation. Methods/design This single-blind, randomised controlled trial will involve people with dementia living in nursing homes of the Canton Ticino (Switzerland). Participants will be randomised to one of two interventions: Doll Therapy Intervention or Sham Intervention with a non-anthropomorphic object, using a 1:1 allocation ratio. The two interventions will consist of 30 daily sessions lasting an hour at most, led by a trained nurse for an hour at most. We will enrol 64 participants per group, according to power analysis using an estimated medium effect size (f = 0.25), an alpha level of 0.05, and a power of 0.8. The primary goal is to test the efficacy of the Doll Therapy Intervention versus the Sham Intervention as the net change in the following measures from baseline to 30 days (blinded outcomes): the Neuropsychiatric Inventory-Nursing Home administered by a trained psychologist blinded to group assignment, the professional caregivers’ perceived stress scale of the Neuropsychiatric Inventory-Nursing Home, patients’ physiological indices of stress (salivary cortisol, blood pressure and heart rate) and interactive behaviours. The secondary goal is to assess the relationship between attachment styles of people with dementia (detected by means of the Adult Attachment Interview to the patients’ offspring) and their caregiving behaviours shown during the Doll Therapy Intervention. Discussion This is the first single-blind, randomised controlled trial on the efficacy of Doll therapy for dementia and an explanatory model of the response of people with dementia to doll presentation. Trial registration ClinicalTrials.gov, ID: NCT03224143. Retrospectively registered on 21 July 2017

A pharmacokinetic analysis of CDPcholine has been carried out treating either rats or dogs by oral administration with the double labelled molecule. [ methyl - 14 C,5- 3 H]CDPcholine represents a useful tool to test the structural integrity of this compound during the transmembrane transport and to follow the metabolic fate of cytidine and choline fragments. Furthermore, the identification of the labelled metabolites of the exogenously administered CDPcholine in the various organs allows us to draw inferences about its pharmacological mechanism(s). These studies appear of great interest in view of the extensive therapeutic use of the molecule in the treatment of several CNS pathologies including traumatic brain injury. The results of this work can be summarized as follows. (a) The molecule is rapidly cleaved at the level of the pyrophosphate bridge and a fast uptake of the hydrolytic products occurs. (b) The metabolism of the molecule is characterized by a differential utilization of the two moieties by the various organs. Liver is the most active organ utilizing in CDPcholine with a preferential uptake of the choline fragment. (c) The [ 3 H]cytidine moiety, in all the organs examined, appears to be incorporated into the nucleic acid fraction via the cytidine nucleotide pool. The [ 14 C]choline moiety is in part converted into betaine, which in turn acts as methyl donor to homocysteine, yielding [ 14 C]methionine, subsequently incorporated into proteins. The time-dependent increase in the labelling of phospholipids is indicative of a recycling of choline methyl groups via CDPcholine and/or S -adenosylmethionine. (d) The uptake of CDPcholine by the brain is relatively low; however, a good metabolic utilization of the drug can be observed. The salvage of the choline moeity in de novo phospholipid biosynthesis is indeed highly operative in this organ.