Vangrankin4961

BACKGROUND RTS,S is the leading malaria vaccine candidate, but only confers partial efficacy against malaria in children. RTS,S is based on the major Plasmodium falciparum sporozoite surface antigen, circumsporozoite protein (CSP). The induction of anti-CSP antibodies is important for protection, however, it is unclear how these protective antibodies function. METHODS We quantified the induction of functional anti-CSP antibody responses in healthy malaria-naïve adults (N=45) vaccinated with RTS,S/AS01. This included the ability to mediate effector functions via the fragment crystallizable (Fc) region, such as interacting with human complement proteins and Fcγ-receptors (FcγRs) that are expressed on immune cells, which promote various immunological functions. RESULTS Our major findings were i) RTS,S-induced antibodies mediate Fc-dependent effector functions, ii) functional antibodies were generally highest after the second vaccine dose; iii) functional antibodies targeted multiple regions of CSP, iv) participants with higher levels of functional antibodies had a reduced probability of developing parasitemia following homologous challenge (p less then 0.05); v) non-protected subjects had higher levels of anti-CSP IgM. CONCLUSIONS Our data suggests a role for Fc-dependent antibody effector functions in RTS,S-induced immunity. Enhancing the induction of these functional activities may be a strategy to improve the protective efficacy of RTS,S or other malaria vaccines. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.Prefrontal cortex (PFC) is highly influenced by the inputs from ventral tegmental area (VTA); however, how the projection from VTA impacts PFC neurons and how the synaptically released dopamine affects PFC activity are largely unclear. Using optogenetics and electrophysiological approaches, we examined the impact of VTA stimulation on PFC principal neurons and parvalbumin-positive (PV+) interneurons and the modulatory role of dopamine. We found that the brief activation of the VTA-PFC circuit immediately induced action potential firing, which was mediated by glutamatergic transmission. However, strong stimulation of VTA gradually induced a marked and prolonged enhancement of the excitability of PFC PV+ interneurons and a modest and short-lived enhancement of the excitability of PFC principal neurons. Blocking dopamine receptors (DARs) shortened the VTA excitation of PFC PV+ interneurons and prolonged the VTA excitation of PFC principal neurons. Blocking GABAA receptors induced a similar effect as DAR antagonists in PFC principal neurons, suggesting that the dopaminergic effect is through influencing the inhibitory transmission system. These results have revealed a role of dopamine in regulating the temporal dynamics of excitation/inhibition balance in VTA-PFC circuit, which provides insights into the functional consequence of activating dopamine system in the mesocortical system. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Multidomain lifestyle interventions (including combinations of physical exercise, cognitive training and nutritional guidance) are attracting increasing research attention for reducing the risk of Alzheimer's disease (AD). Here we examined for the first time the cross-sectional relationship between cortical β-amyloid (Aβ) and multidomain lifestyle interventions (nutritional and exercise counselling and cognitive training), omega 3 polyunsaturated fatty acid (n-3 PUFA) supplementation or their combination in 269 participants of the Multidomain Alzheimer Preventive Trial (MAPT). In adjusted multiple linear regression models, compared to the control group (receiving placebo alone), cortical Aβ, measured once during follow-up (mean 512.7 ± 249.6 days post-baseline), was significantly lower in the groups receiving multidomain lifestyle intervention + placebo (mean difference, -0.088, 95 % CI, -0.148,-0.029, p = 0.004) or multidomain lifestyle intervention + n-3 PUFA (-0.100, 95 % CI, -0.160,-0.041, p = 0.001), but there was no difference in the n-3 PUFA supplementation alone group (-0.011, 95 % CI, -0.072,0.051, p = 0.729). Secondary analysis provided mixed results. Our findings suggest that multidomain interventions both with and without n-3 PUFA supplementation might be associated with lower cerebral Aβ. Future trials should investigate if such multidomain lifestyle interventions are causally associated with a reduction or the prevention of the accumulation of cerebral Aβ.BACKGROUND Effective and measurable participant recruitment methods are urgently needed for clinical studies in Alzheimer's disease. OBJECTIVES To develop methods for measuring recruitment tactics and evaluating effectiveness. METHODS Recruitment tactics for the Alzheimer's Disease Neuroimaging Initiative (ADNI3) were measured using web and phone analytics, campaign metrics and survey responses. RESULTS A total of 462 new participants were enrolled into ADNI3 through recruitment efforts. We collected metrics on recruitment activities including 82,003 unique visitors to the recruitment website and 3,335 calls to study phone numbers. The recruitment sources that produced the most screening and enrollment included online advertisements, local radio and newspaper coverage and emails and referrals from registries. CONCLUSIONS Analysis of recruitment activity obtained through tracking methods provided some insight for effective recruitment. ADNI3 can serve as an example of how a data-driven approach to centralized participant recruitment can be utilized to facilitate clinical research.BACKGROUND Cognitive interventions have the potential to enhance cognition among healthy older adults. However, little attention has been paid to the effect of cognitive training (CT) on mood and activities of daily living (ADL). OBJECTIVES To assess the effectiveness of a multicomponent CT using a training program of executive functions, attention, memory and visuospatial functions (TEAM-V Program) on cognition, mood and instrumental ADL. DESIGN A randomized, single-blinded, treatment-as-usual controlled trial. Ulonivirine nmr SETTING Geriatric clinic in Bangkok, Thailand. PARTICIPANTS 77 nondemented community-dwelling older adults (mean age 65.7±4.3 years). INTERVENTION The CT (TEAM-V) program or the treatment-as-usual controlled group. The TEAM-V intervention was conducted over 5 sessions, with a 2-week interval between each session. Of 77 participants randomized (n=40 the TEAM-V program; n=37 the control group). MEASUREMENTS The Thai version of Montreal Cognitive Assessment (MoCA), The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Thai version of Hospital Anxiety and Depression Scale (HADS) and The Chula ADL were used to assess at baseline, 6 months and 1 year.