Status report of the first AMS laboratory in the Czech Republic at the Nuclear Physics Institute, Rez.

The first accelerator mass spectrometry (AMS) laboratory in the Czech Republic has been established and put into routine operation in February 2022. Here we briefly describe the facilities available, namely a 300 kV multi-isotope low-energy AMS system (MILEA) capable of determination 10Be, 14C, 26Al, 41Ca, 129I, isotopes of U, especially 236U, Pu and other actinoids, and accessories for 14C measurements, which include a gas interface system, a preparative gas chromatography system for compound-specific radiocarbon dating analysis, and an isotope-ratio mass spectrometer. The first results achieved for separation and measurement of the above radionuclides (except for 41Ca) are also reported, with the main focus on 14C measurements. A specimen breakdown of 729 graphitised samples analysed for 14C so far is presented, as well as a proof of measurement stability of the MILEA system obtained by analysis of radiocarbon standards and analytical blanks. For the other radionuclides, well proven or novel procedures for sample preparation and measurement are presented.

Generalizability of cognitive results from clinical trial participants to an older adult population: Addressing external validity.

Introduction: Study inclusion criteria and recruitment practices limit the generalizability of randomized-controlled trial (RCT) results. Statistical modeling could enhance generalizability of outcomes. To illustrate this, the cognition-depression relationship was assessed with and without adjustment relative to the target population of older women. Methods: Randomized participants from four RCTs and non-randomized participants from two cohorts were included in this study. Prediction models estimated probability of being randomized into trials from target populations. These probabilities were used for inverse odds weighting relative to target populations. Weighted linear regression was used to assess the depression-cognition relationship. Results: There was no depression-cognition relationship in the combined randomized sample. After applying weights relative to a representative cohort, negative relationships were observed. After applying weights relative to a non-representative cohort, bias of estimates increased. Discussion: Quantitative approaches to transportability using representative samples may explain the absence of a-priori established relationships in RCTs.

Subclinical carotid artery atherosclerosis and cognitive function in older adults.

BACKGROUND: The combined effects of increased life expectancy and the considerable number of persons reaching old age will magnify the dementia epidemic in the USA. Demonstration that subclinical atherosclerosis precedes and is associated with cognitive impairment suggests a modifiable risk factor for age-associated cognitive impairment and dementia. The purpose of this study is to determine whether subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) is associated with changes in cognitive function over time in older adults. METHODS: This study combined longitudinal data from three clinical trials conducted between 2000 and 2013: the B-Vitamin Atherosclerosis Intervention Trial (BVAIT), the Women's Isoflavone Soy Health (WISH) trial, and the Early versus Late Intervention Trial with Estradiol (ELITE). Participants were recruited from the general population in the Greater Los Angeles area and were free of cardiovascular disease and diabetes; no cognitive or psychiatric exclusion criteria were specified. The same standardized protocol for ultrasound image acquisition and measurement of CIMT was used in all trials. CIMT measurements performed at baseline and 2.5 years were used in these analyses. Cognitive function was assessed at baseline and 2.5 years using a battery of 14 standardized cognitive tests. All clinical trials were conducted at the University of Southern California Atherosclerosis Research Unit, Los Angeles, and had at least 2.5 years of cognitive follow-up. RESULTS: A total of 308 men and 1187 women, mean age of 61 years, were included in the combined longitudinal dataset for the primary analysis. No associations were found between CIMT and cognitive function at baseline or at 2.5 years. There was a weak inverse association between CIMT measured at baseline and change in global cognition assessed over 2.5 years (ß (SE) = - 0.056 (0.028) units per 0.1 mm CIMT, 95% CI - 0.110, - 0.001, p = 0.046). No associations between CIMT at baseline and changes in executive function, verbal memory, or visual memory were found. CONCLUSIONS: In this sample of healthy older adults, our findings suggest an association between subclinical atherosclerosis and change in global cognitive function over 2.5 years. Stronger associations were observed longitudinally over 2.5 years than cross-sectionally. When analysis was stratified by age group (<65 and ≥65 years old), the inverse association remained statistically significant for participants in the older age group. Subclinical atherosclerosis of the carotid artery may be a modifiable correlate of cognitive decline in middle and older age. TRIAL REGISTRATION: BVAIT, NCT00114400 . WISH, NCT00118846 . ELITE, NCT00114517 .

Stability of Different BTBP and BTPhen Extracting or Masking Compounds against γ Radiation.

The radiolytic stability of hydrophobic extracting compounds CyMe4-BTBP and CyMe4-BTPhen and a hydrophilic masking agent (PhSO3H)2-BTPhen, widely employed for trivalent minor actinoid and lanthanoid separation, against γ radiation was tested. Even though the solvent with a promising fluorinated diluent BK-1 provides better extraction properties compared to octan-1-ol, its radiation stability is much lower, and no extraction was observed already after an absorbed dose of 150 kGy (CyMe4-BTBP) or 200 kGy (CyMe4-BTPhen). For the (PhSO3H)2-BTPhen hydrophilic masking agent, the results showed that the rate of radiolytic degradation was significantly higher in 0.25 M HNO3 than in 0.5 M HNO3. For both the hydrophobic and hydrophilic agents, degradation was slower in the presence of both organic and aqueous phases during irradiation.

Nattokinase atherothrombotic prevention study: A randomized controlled trial.

BACKGROUND: Described to be antithrombotic and antihypertensive, nattokinase is consumed for putative cardiovascular benefit. However, no large-scale, long-term cardiovascular study has been conducted with nattokinase supplementation. OBJECTIVE: To determine the effect of nattokinase on subclinical atherosclerosis progression and atherothrombotic biomarkers. METHODS: In this double-blinded trial, 265 individuals of median age 65.3 years, without clinical evidence of cardiovascular disease (CVD) were randomized to oral nattokinase 2,000 fibrinolytic units or matching placebo. Primary outcome was rate of change in subclinical atherosclerosis measured by serial carotid ultrasound every 6 months as carotid artery intima-media thickness (CIMT) and carotid arterial stiffness (CAS). Additional outcomes determined at least every 6 months were clinical parameters including blood pressure and laboratory measures including metabolic factors, blood rheology parameters, blood coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage cellular activation markers. RESULTS: After median 3 years of randomized treatment, annualized rate of change in CIMT and CAS did not significantly differ between nattokinase supplementation and placebo. Additionally, there was no significant effect of nattokinase supplementation on blood pressure or any laboratory determination. CONCLUSIONS: Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.

Apolipoprotein E4 genotype in combination with poor metabolic profile is associated with reduced cognitive performance in healthy postmenopausal women: implications for late onset Alzheimer's disease.

OBJECTIVE: We hypothesized the association of metabolic profile on cognition in postmenopausal women will be greater among ApoE4 carriers compared with noncarriers. METHODS: Metabolic biomarkers and measures of global cognition, executive functions, and verbal memory, collected among postmenopausal females, were used in this analysis. Clustering analyses of metabolic biomarkers revealed three phenotypes: healthy, predominantly hypertensive, and poor metabolic with (borderline normal laboratory values). General linear models tested whether an association of metabolic cluster with cognition differed by ApoE4 genotype. RESULTS: In the total sample of 497 women, verbal memory was lower in the poor metabolic cluster (P = 0.04). Among ApoE4+ women, performance in all cognitive domains was lowest in the poor metabolic cluster. Differences in executive functions among metabolic clusters were detected only in ApoE4+ women (P value for interaction = 0.003). CONCLUSIONS: In a general population of postmenopausal women, association between poor metabolic profile with reduction in cognitive performance is more apparent in women who carry an ApoE4 allele. These data indicate a window of opportunity for interventions to reverse the trajectory of the preclinical phase of Alzheimer's disease.

Extraction of minor actinides, lanthanides and other fission products by silica-immobilized BTBP/BTPhen ligands.

Novel BTBP [bis-(1,2,4-triazin-3-yl)-2,2'-bipyridine]/BTPhen [bis-(1,2,4-triazin-3-yl)-1,10-phenanthroline] functionalized silica gels have been developed to extract minor actinides, lanthanides and other fission products. BTPhen functionalized silica gel is capable of near-quantitative removal of Am(iii) in the presence of Eu(iii) from aqueous HNO3, while BTBP functionalized silica gel is able to remove problematic corrosion and fission products that are found in PUREX raffinates.

Effect of Reproductive History and Exogenous Hormone Use on Cognitive Function in Mid- and Late Life.

OBJECTIVES: To investigate the association between reproductive history indicators of hormonal exposure, including reproductive period, pregnancy, and use of hormonal contraceptives, and mid- and late-life cognition in postmenopausal women. DESIGN: Analysis of baseline data from two randomized clinical trials: the Women's Isoflavone Soy Health and the Early vs Late Intervention Trial of Estradiol. SETTING: University academic research center. PARTICIPANTS: Naturally menopausal women (N = 830). MEASUREMENTS: Participants were uniformly evaluated using a cognitive battery and a structured reproductive history questionnaire. Outcomes were composite scores for verbal episodic memory, executive function, and global cognition. Reproductive variables included ages at pregnancies, menarche, and menopause; reproductive period; number of pregnancies; and use of hormones for contraception and menopausal symptoms. Multivariable linear regression was used to evaluate associations between cognitive scores (dependent variable) and reproductive factors (independent variables), adjusting for age, race and ethnicity, income, and education. RESULTS: On multivariable modeling, age at menarche of 13 and older was inversely associated with global cognition (P = .05). Last pregnancy after age 35 was positively associated with verbal memory (P = .03). Use of hormonal contraceptives was positively associated with global cognition (P trend = .04), and verbal memory (P trend = .007). The association between hormonal contraceptive use and verbal memory and executive function was strongest for more than 10 years of use. Reproductive period was positively associated with global cognition (P = .04) and executive function (P = .04). CONCLUSION: In this sample of healthy postmenopausal women, reproductive life events related to sex hormones, including earlier age at menarche, later age at last pregnancy, longer reproductive period, and use of oral contraceptives are positively related to aspects of cognition in later life.

Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis.

OBJECTIVE: To test the hypothesis that effects of estrogen-containing hormone therapy on cognitive abilities differ between postmenopausal women near to, and further from, menopause. METHODS: In this randomized, double-blind, placebo-controlled trial, healthy women within 6 years of menopause or 10+ years after menopause were randomly assigned to oral 17ß-estradiol 1 mg/d or placebo. Women with a uterus received cyclic micronized progesterone vaginal gel or placebo. The primary outcome assessed at 2.5 and 5 years, compared between treatment groups, was change in a standardized composite of neuropsychological test scores assessing verbal episodic memory. Secondary outcomes assessed executive functions and global cognition. RESULTS: A total of 567 women were included in modified intention-to-treat analyses after a mean treatment duration of 57 months. For verbal memory, the mean estradiol minus placebo standardized difference in composite scores (-0.06, 95% confidence interval -0.22 to 0.09) was not significant (2-tailed p = 0.33). Differences were similar in early and late postmenopause groups (2-tailed interaction p = 0.88). Interactions between postmenopause groups and differences between treatment groups were not significant for executive functions or global cognition. CONCLUSIONS: Estradiol initiated within 6 years of menopause does not affect verbal memory, executive functions, or global cognition differently than therapy begun 10+ years after menopause. Estradiol neither benefits nor harms these cognitive abilities regardless of time since menopause. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that estradiol initiated within 6 years of menopause does not affect cognition at 2.5 years differently than estradiol initiated 10+ years after menopause.

Synthesis and Screening of Modified 6,6'-Bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydrobenzo[e][1,2,4]triazin-3-yl)-2,2'-bipyridine Ligands for Actinide and Lanthanide Separation in Nuclear Waste Treatment.

Effects of chloro and bromo substitution at the 4-position of the pyridine ring of 6,6'-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydrobenzo[e][1,2,4]triazin-3-yl)-2,2'-bipyridine (CyMe4-BTBP) have been studied with regard to the extraction of Am(III) from Eu(III) and Cm(III) from 0.1-3 M HNO3. Similarly to CyMe4-BTBP, a highly efficient (DAm > 10 at 3 M HNO3) and selective (SFAm/Eu > 100 at 3 M HNO3) extraction was observed for Cl-CyMe4-BTBP and Br-CyMe4-BTBP in 1-octanol but in the absence of a phase-transfer agent.

Association of bilateral oophorectomy with cognitive function in healthy, postmenopausal women.

OBJECTIVE: To investigate the association between bilateral oophorectomy and cognitive performance in healthy, older women. DESIGN: Retrospective analysis of clinical trial data. SETTING: Academic research institution. PATIENT(S): Healthy postmenopausal women without signs or symptoms of cardiovascular disease or diabetes (n = 926). INTERVENTION(S): Randomized interventions (not the focus of this analysis) in analyzed trials included B-vitamins, soy isoflavones, oral estradiol, and matching placebos. MAIN OUTCOME MEASURE(S): Measures in five cognitive domains (executive functions, semantic memory, logical memory, visual memory, and verbal learning) and global cognitive function. RESULT(S): Using data from three clinical trials conducted under uniform conditions, bilateral oophorectomy and its timing were analyzed cross-sectionally and longitudinally in relation to cognitive function in linear regression models. Covariates included age, education, race/ethnicity, body mass index, trial, and randomized treatment (in longitudinal models). Duration of menopausal hormone use was considered as a possible mediator and effect modifier. Median age of oophorectomy was 45 years. When evaluating baseline cognition, we found that surgical menopause after 45 years of age was associated with lower performance in verbal learning compared with natural menopause. Evaluating the change in cognition over approximately 2.7 years, surgical menopause was associated with performance declines in visual memory for those who had an oophorectomy after 45 years of age and in semantic memory for those who had oophorectomy before 45 years of age compared with natural menopause. Oophorectomy after natural menopause was not associated with cognitive performance. Adjustment for duration of hormone use did not alter these associations. CONCLUSION(S): Cognitive associations with ovarian removal vary by timing of surgery relative to both menopause and age.

Identifying postmenopausal women at risk for cognitive decline within a healthy cohort using a panel of clinical metabolic indicators: potential for detecting an at-Alzheimer's risk metabolic phenotype.

Detecting at-risk individuals within a healthy population is critical for preventing or delaying Alzheimer's disease. Systems biology integration of brain and body metabolism enables peripheral metabolic biomarkers to serve as reporters of brain bioenergetic status. Using clinical metabolic data derived from healthy postmenopausal women in the Early versus Late Intervention Trial with Estradiol (ELITE), we conducted principal components and k-means clustering analyses of 9 biomarkers to define metabolic phenotypes. Metabolic clusters were correlated with cognitive performance and analyzed for change over 5 years. Metabolic biomarkers at baseline generated 3 clusters, representing women with healthy, high blood pressure, and poor metabolic phenotypes. Compared with healthy women, poor metabolic women had significantly lower executive, global and memory cognitive performance. Hormone therapy provided metabolic benefit to women in high blood pressure and poor metabolic phenotypes. This panel of well-established clinical peripheral biomarkers represents an initial step toward developing an affordable, rapidly deployable, and clinically relevant strategy to detect an at-risk phenotype of late-onset Alzheimer's disease.

Hydrophilic sulfonated bis-1,2,4-triazine ligands are highly effective reagents for separating actinides(iii) from lanthanides(iii) via selective formation of aqueous actinide complexes.

We report the first examples of hydrophilic 6,6'-bis(1,2,4-triazin-3-yl)-2,2'-bipyridine (BTBP) and 2,9-bis(1,2,4-triazin-3-yl)-1,10-phenanthroline (BTPhen) ligands, and their applications as actinide(iii) selective aqueous complexing agents. The combination of a hydrophobic diamide ligand in the organic phase and a hydrophilic tetrasulfonated bis-triazine ligand in the aqueous phase is able to separate Am(iii) from Eu(iii) by selective Am(iii) complex formation across a range of nitric acid concentrations with very high selectivities, and without the use of buffers. In contrast, disulfonated bis-triazine ligands are unable to separate Am(iii) from Eu(iii) in this system. The greater ability of the tetrasulfonated ligands to retain Am(iii) selectively in the aqueous phase than the corresponding disulfonated ligands appears to be due to the higher aqueous solubilities of the complexes of the tetrasulfonated ligands with Am(iii). The selectivities for Am(iii) complexation observed with hydrophilic tetrasulfonated bis-triazine ligands are in many cases far higher than those found with the polyaminocarboxylate ligands previously used as actinide-selective complexing agents, and are comparable to those found with the parent hydrophobic bis-triazine ligands. Thus we demonstrate a feasible alternative method to separate actinides from lanthanides than the widely studied approach of selective actinide extraction with hydrophobic bis-1,2,4-triazine ligands such as CyMe4-BTBP and CyMe4-BTPhen.

Effective separation of Am(III) and Eu(III) from HNO3 solutions using CyMe4-BTPhen-functionalized silica-coated magnetic nanoparticles.

It has been shown that CyMe4-BTPhen-functionalized silica-coated maghemite (γ-Fe2O3) magnetic nanoparticles (MNPs) are capable of quantitative separation of Am(III) from Eu(III) from HNO3 solutions. These MNPs also show a small but significant selectivity for Am(III) over Cm(III) with a separation factor of around 2 in 4 M HNO3. The water molecule in the cavity of the BTPhen may also play an important part in the selectivity.

Associations between urine excretion of isoflavonoids and cognition in postmenopausal women in the Women's Isoflavone Soy Health clinical trial.

OBJECTIVES: To determine effect of change in urine excretion of isoflavonoids on cognitive change. DESIGN: Post hoc analysis of isoflavonoid exposure (mean 2.7 years) during the randomized, placebo-controlled, double-blind Women's Isoflavone Soy Health trial. SETTING: General community. PARTICIPANTS: Healthy postmenopausal women (N = 350). INTERVENTION: Twenty-five grams of isoflavone-rich soy protein (91 mg of aglycone weight isoflavones: 52 mg genistein, 36 mg daidzein, 3 mg glycitein) or milk protein-matched placebo provided daily. MEASUREMENTS: Overnight urine excretion, fasting plasma levels of isoflavonoids, and cognitive function measured at baseline and endpoint. RESULTS: Three hundred women (age: mean 61, range 45-92) completed both cognitive assessments and did not use hormone replacement therapy during the trial. Mean on-trial change from baseline in urine excretion of isoflavonoids was not significantly associated with change in a composite score of global cognition (P = .39). Secondary analyses indicated that change in urine excretion of isoflavonoids was inversely associated with change in a factor score representing general intelligence (P = .02) but not with factor scores representing verbal or visual episodic memory. Mean differences in this general intelligence factor score between women in the lowest and highest quartiles of isoflavonoid change were equivalent to an approximate 4.4-year age-associated decline. Analyses based on plasma isoflavonoid levels yielded similar but attenuated results. CONCLUSION: In healthy postmenopausal women, long-term changes in isoflavonoids are not associated with global cognition, supporting clinical trial results, although greater isoflavonoid exposure from dietary supplements is associated with decrements in general intelligence but not memory; this finding requires confirmation in future studies.

Components of air pollution and cognitive function in middle-aged and older adults in Los Angeles.

While experiments in animals demonstrate neurotoxic effects of particulate matter (PM) and ozone (O3), epidemiologic evidence is sparse regarding the relationship between different constituencies of air pollution mixtures and cognitive function in adults. We examined cross-sectional associations between various ambient air pollutants [O3, PM2.5 and nitrogen dioxide (NO2)] and six measures of cognitive function and global cognition among healthy, cognitively intact individuals (n=1496, mean age 60.5 years) residing in the Los Angeles Basin. Air pollution exposures were assigned to each residential address in 2000-06 using a geographic information system that included monitoring data. A neuropsychological battery was used to assess cognitive function; a principal components analysis defined six domain-specific functions and a measure of global cognitive function was created. Regression models estimated effects of air pollutants on cognitive function, adjusting for age, gender, race, education, income, study and mood. Increasing exposure to PM2.5 was associated with lower verbal learning (ß=-0.32 per 10 µg/m(3) PM2.5, 95% CI=-0.63, 0.00; p=0.05). Ambient exposure to NO2 >20 ppb tended to be associated with lower logical memory. Compared to the lowest level of exposure to ambient O3, exposure above 49 ppb was associated with lower executive function. Including carotid artery intima-media thickness, a measure of subclinical atherosclerosis, in models as a possible mediator did not attenuate effect estimates. This study provides support for cross-sectional associations between increasing levels of ambient O3, PM2.5 and NO2 and measures of domain-specific cognitive abilities.

Cognition, mood, and physiological concentrations of sex hormones in the early and late postmenopause.

Variations in the hormonal milieu after menopause may influence neural processes concerned with cognition, cognitive aging, and mood, but findings are inconsistent. In particular, cognitive effects of estradiol may vary with time since menopause, but this prediction has not been assessed directly using serum hormone concentrations. We studied 643 healthy postmenopausal women not using hormone therapy who were recruited into early (<6 y after menopause) and late (10+ y after menopause) groups. Women were administered a comprehensive neuropsychological battery and assessed with the Center for Epidemiologic Studies Depression Scale. They provided serum for free estradiol, estrone, progesterone, free testosterone, and sex hormone binding globulin measurements. Cognitive outcomes were standardized composite measures of verbal episodic memory, executive functions, and global cognition. Covariate-adjusted linear regression analyses were conducted for each hormone separately and after adjustment for other hormone levels. Endogenous sex steroid levels were unassociated with cognitive composites, but sex hormone binding globulin was positively associated with verbal memory. Results for early and late groups did not differ significantly, although progesterone concentrations were significantly positively associated with verbal memory and global cognition in early group women. Hormone concentrations were not significantly related to mood. Results fail to support the hypothesis that temporal proximity to menopause modifies the relation between endogenous serum levels of estradiol and verbal memory, executive functions, or global cognition. Physiological variations in endogenous postmenopausal levels of sex steroid hormones are not substantially related to these aspects of cognition or mood; positive associations for progesterone and sex hormone binding globulin merit additional study.

Radiation formation of colloidal silver particles in aqueous systems.

This paper reports on the formation of silver nanoparticles initiated by gamma and UV radiation in various aqueous solutions. Inorganic precursors were used for radiation and/or photochemical reduction of Ag(+) ions to a metallic form. The influence of various parameters on the nucleation and formation of colloid particles was studied. Attention was also focused on the composition of the irradiated solution. Aliphatic alcohols were used as scavengers of OH radicals and other oxidizing species. The influence of the stabilizers on the formation and stability of the nanoparticles was studied.