Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk. The current analysis examined the effect of GTE consumption on liver injury in 1,021 participants (513 in GTE and 508 in placebo arm) with normal baseline levels of liver enzymes. Among women in the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence interval (CI), 3.6-7.1] and aspartate aminotransferase increased by 3.8 U/L (95% CI, 2.5-5.1), which were significantly higher than those among women in the placebo arm (both < 0.001). Overall, 26 (5.1%) women in GTE developed moderate or more severe abnormalities in any liver function measure during the intervention period, yielding an OR of 7.0 (95% CI, 2.4-20.3) for developing liver function abnormalities as compared with those in the placebo arm. ALT returned to normal after dechallenge and increased again after one or more rechallenges with GTE. The rise-fall pattern of liver enzyme values following the challenge-dechallenge cycles of GTE consumption strongly implicates the effect of high-dose GTE on liver enzyme elevations. .

IntroductionBone marrow-derived multipotent adult progenitor cells (MAPCs) are adult allogeneic adherent stem cells currently investigated clinically for use in acute respiratory distress syndrome (ARDS). To date, there is no agreement on which is the best method for stem cells delivery in ARDS. Here, we compared the efficacy of two different methods of administration and biodistribution of MAPC for the treatment of ARDS in a sheep model.MethodsMAPC were labelled with [18F] fluoro-29-deoxy-D-glucose and delivered by endobronchial (EB) or intravenous route 1 hour after lipopolysaccharide infusion in sheep mechanically ventilated. PET/CT images were acquired to determine the biodistribution and retention of the cells at 1 and 5 hours of administration.ResultsThe distribution and retention of the MAPC was dependent on the method of cell administration. By EB route, PET images showed that MAPC remained at the site of administration and no changes were observed after 5 hours, whereas with intravenous route, the cells had broad biodistribution to different organs, being the lung the main organ of retention at 1 and 5 hours. MAPC demonstrated an equal effect on arterial oxygenation recovery by either route of administration.ConclusionThe EB or intravenous routes of administration of MAPC are both effective for the treatment of ARDS in an acute sheep model, and the effect of MAPC therapy is not dependent of parenchymal integration or systemic biodistribution.

Introduction The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB‐CB) was developed to be a common assessment metric across a broad array of research studies. We investigated associations between NIHTB‐CB and brain amyloid and tau deposition in cognitively unimpaired older adults. Methods One hundred eighteen community‐based volunteers completed magnetic resonance imaging (MRI), Pittsburgh compound B (PiB)‐PET (positron emission tomography) and AV‐1451‐PET neuroimaging, a neuropsychological evaluation, NIHTB‐CB, and the Clinical Dementia Rating (CDR) scale. Demographically adjusted regression models evaluated cognition–biomarker associations; standardized effect sizes allowed comparison of association strength across measures. Results No NIHTB‐CB measures were associated with amyloid deposition. NIHTB‐CB measures of fluid cognition, including Pattern Comparison Processing Speed, Dimensional Change Card Sort, and Fluid Cognition Composite, were associated with tau deposition in higher Braak regions. Pattern Comparison Processing Speed was the most robust association with sensitivity analyses. Discussion NIHTB‐CB tasks of processing speed and executive functions may be sensitive to pathologic tau deposition on imaging in normal aging.

Introduction Centiloid standardization was developed to establish a quantitative outcome measure of amyloid burden that could accommodate the integration of different amyloid positron emission tomography radiotracers or different methods of quantifying the same tracer. The goal of this study was to examine the use of Centiloids for establishing amyloid classification cutoffs for differing region-of-interest (ROI) delineation schemes. Methods Using ROIs from hand-drawn delineation in native space as the gold standard, we compared standard uptake value ratios obtained from the 6 hand-drawn ROIs that determine amyloid-positivity classification with standard uptake value ratio obtained from 3 different automated techniques (FreeSurfer, Statistical Parametric Mapping, and superimposed hand-drawn ROIs in Pittsburgh Compound B template space). We tested between-methods reliability using repeated measures models and intraclass correlation coefficients. Results We found high reliability between the hand-drawn standard method and other methods for almost all the regions considered. However, small differences in standard uptake value ratio were found to lead to unreliable classifications when the hand-drawn native space-derived cutoffs were used across other ROI delineation methods. Discussion The use of Centiloid standardization greatly improved the agreement of Pittsburgh Compound B classification across methods and may serve as an alternative method for applying cutoffs across methodologically different outcomes.

Down syndrome (DS) predisposes individuals to early Alzheimer’s disease (AD). Using [11C]PiB, a pattern of striatal amyloid-beta (Aβ) that is elevated relative to neocortical binding has been reported, similar to that of non-demented autosomal dominant AD mutation carriers. However, it is not known if changes in striatal and neocortical [11C]PiB retention differ over time in a non-demented DS population when compared to changes in a non-demented elderly (NDE) population. The purpose of this work was to assess longitudinal changes in trajectories of Aβ in a non-demented DS compared to an NDE cohort. The regional trajectories for anterior ventral striatum (AVS), frontal cortex (FRC) and precuneus (PRC) [11C]PiB retention were explored over time using linear mixed effects models with fixed effects of time, cohort and time-by-cohort interactions and subject as random effects. Significant differences between DS and NDE cohort trajectories for all three ROIs were observed (p<0.05), with the DS cohort showing a faster accumulation in AVS and slower accumulation in FRC and PRC compared to the NDE cohort. These data add to the previously reported distinct pattern of early striatal deposition not commonly seen in sporadic AD by demonstrationg that individuals with DS may also accumulate Aβ at a rate faster in AVS when compared to NDE subjects.

To characterize the influence of APOE genotype on cerebral Aβ load and longitudinal Aβ trajectories, [ 11 C]PiB PET imaging studies were performed in a cohort of 428 participants with known APOE genotype and a range of clinical diagnoses from cognitively normal elderly to Alzheimer's disease (AD). [ 11 C]PiB PET imaging was used to assess amyloid load in a clinically heterogeneous cohort of 428 elderly participants. Serial [ 11 C]PiB data and a repeated measures

Introduction Equol, a metabolite of a soy isoflavone transformed by the gut microbiome, is anti‐oxidant and anti‐amyloidogenic. We assessed the associations of equol with white matter lesion normalized to total brain volume (WML%) and amyloid beta (Aβ) deposition. Methods From 2016 to 2018, 91 cognitively normal elderly Japanese aged 75 to 89 underwent brain magnetic resonance imaging and positron emission tomography using 11 C‐Pittsburgh compound‐B. Serum equol was measured using stored samples from 2008 to 2012. Equol producers were defined as individuals with serum levels >0. Producers were further divided into high (> the median) and low (≤ the median) producers. Results The median (interquartile range) WML% was 1.10 (0.59 to 1.61); 24.2% were Aβ positive, and 51% were equol producers. Equol‐producing status (non‐producers, low and high) was significantly inversely associated with WML%: 1.19, 0.89, and 0.58, respectively (trend P < .01). Equol‐producing status was not associated with Aβ status. Discussion A randomized‐controlled trial of equol targeting WML volume is warranted.

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