Reassignment of the Photoelectron Spectrum of Methylketene Using a Hybrid Model of Harmonic and Anharmonic Oscillators to Compute Franck-Condon Factors.

We constructed a hybrid model of harmonic and anharmonic oscillators to compute Franck-Condon factors and interpret the photoelectron spectrum of methylketene. The equilibrium structures of methylketene and its cation were optimized, and then, the harmonic and anharmonic vibrational frequencies were computed using the B3LYP, PBE0, APFD, and ωB97XD approaches of the density functional theory. The photoelectron spectrum of methylketene was simulated by computing the Franck-Condon factors with both the harmonic and hybrid models. The adiabatic ionization energy of methylketene was computed by using the CCSD(T) approach extrapolating to the complete basis set limit. The simulated photoelectron spectra are consistent with those from the experiment for both the harmonic and hybrid models. However, the error in band positions is reduced by using the hybrid model. The computed adiabatic ionization energies of methylketene are in agreement with the experiment, with the smallest error being 0.017 eV. Our interpretation based on the theoretical spectrum led to the reassignment of the experimental photoelectron spectrum of methylketene.

Interactive effects of locus coeruleus structure and catecholamine synthesis capacity on cognitive function.

Background: The locus coeruleus (LC) produces catecholamines (norepinephrine and dopamine) and is implicated in a broad range of cognitive functions including attention and executive function. Recent advancements in magnetic resonance imaging (MRI) approaches allow for the visualization and quantification of LC structure. Human research focused on the LC has since exploded given the LC's role in cognition and relevance to current models of psychopathology and neurodegenerative disease. However, it is unclear to what extent LC structure reflects underlying catecholamine function, and how LC structure and neurochemical function are collectively associated with cognitive performance. Methods: A partial least squares correlation (PLSC) analysis was applied to 19 participants' LC structural MRI measures and catecholamine synthesis capacity measures assessed using [18F]Fluoro-m-tyrosine ([18F]FMT) positron emission tomography (PET). Results: We found no direct association between LC-MRI and LC-[18F]FMT measures for rostral, middle, or caudal portions of the LC. We found significant associations between LC neuroimaging measures and neuropsychological performance that were driven by rostral and middle portions of the LC, which is in line with LC cortical projection patterns. Specifically, associations with executive function and processing speed arose from contributions of both LC structure and interactions between LC structure and catecholamine synthesis capacity. Conclusion: These findings leave open the possibility that LC MRI and PET measures contribute unique information and suggest that their conjoint use may increase sensitivity to brain-behavior associations in small samples.

Effects of Adult Age and Functioning of the Locus Coeruleus Norepinephrinergic System on Reward-Based Learning.

Age-related impairments in value representations and updating during decision-making and reward-based learning are often related to age-related attenuation in the catecholamine system such as dopamine (DA) and norepinephrine (NE). However, it is unclear to what extent age-related declines in NE functioning in humans affect reward-based decision-making. We conducted a probabilistic decision-making task and applied a Q-learning model to investigate participants' anticipatory values and value sensitivities. Task-related pupil dilations and locus coeruleus (LC) magnetic resonance imaging (MRI) contrast, which served as a potential window of the LC-NE functions, were assessed in younger and older adults. Results showed that in both choice and feedback phases, younger adults' (N = 42, 22 males) pupil dilations negatively correlated with anticipatory values, indicating uncertainty about outcome probabilities. Uncertainty-evoked pupil dilations in older adults (N = 41, 27 males) were smaller, indicating age-related impairments in value estimation and updating. In both age groups, participants who showed a larger uncertainty-evoked pupil dilation exhibited a higher value sensitivity as reflected in the ß parameter of the reinforcement Q-learning model. Furthermore, older adults (N = 34, 29 males) showed a lower LC-MRI contrast than younger adults (N = 25, 15 males). The LC-MRI contrast positively correlated with value sensitivity only in older but not in younger adults. These findings suggest that task-related pupillary responses can reflect age-related deficits in value estimation and updating during reward-based decision-making. Our evidence with the LC-MRI contrast further showed the age-related decline of the LC structure in modulating value representations during reward-based learning.SIGNIFICANCE STATEMENT Age-related impairments in value representation and updating during reward-based learning are associated with declines in the catecholamine modulation with age. However, it is unclear how age-related declines in the LC-NE system may affect reward-based learning. Here, we show that compared with younger adults, older adults exhibited reduced uncertainty-induced pupil dilations, suggesting age-related deficits in value estimation and updating. Older adults showed a lower structural MRI of the LC contrast than younger adults, indicating age-related degeneration of the LC structure. The association between the LC-MRI contrast and value sensitivity was only observed in older adults. Our findings may demonstrate a pioneering model to unravel the role of the LC-NE system in reward-based learning in aging.

Predictors of personal recovery for individuals with schizophrenia spectrum disorders living in the community.

INTRODUCTION: Personal recovery is a complex construct frequently used as outcome measure in people with schizophrenia spectrum disorders. This study examined potential predictors of personal recovery using the two most common assessment tools for people with schizophrenia spectrum disorders living in the community: the Chinese version of the Questionnaire about the Process of Recovery and the Chinese version of the Recovery Assessment Scale. METHODS: Ninety-one individuals (57 women) diagnosed with schizophrenia spectrum disorders participated in the study (mean age: 47.41 ± 9.41 years). All participants lived in the community and received community psychiatric services. The participants were evaluated via interviews, questionnaires and standardized assessments. Potential predictors included four domains: personal, disease-related, functional and social. Stepwise multiple linear regression was used to analyse the potential predictors of the recovery and recovery assessment scale. RESULTS: Resilience and social support were the only significant predictors of the Chinese versions of the Questionnaire about the Process of Recovery and Chinese version of the Recovery Assessment Scale. The primary predictor of the Chinese version of the Questionnaire about the Process of Recovery was social support from family and institutional staff. Conversely, resilience was the major predictor of the Chinese version of the Recovery Assessment Scale. DISCUSSION: For people with schizophrenia spectrum disorders living in the community, social support and resilience significantly predicted personal recovery. Age, educational level, disease-related and functional factors were not significant predictors of personal recovery. Therefore, it is important to develop successful personal recovery-oriented practices that enhance resilience and promote social support.

Older adults process the probability of winning sooner but weigh it less during lottery decisions.

Empirical evidence has shown that visually enhancing the saliency of reward probabilities can ease the cognitive demands of value comparisons and improve value-based decisions in old age. In the present study, we used a time-varying drift diffusion model that includes starting time parameters to better understand (1) how increasing the saliency of reward probabilities may affect the dynamics of value-based decision-making and (2) how these effects may interact with age. We examined choices made by younger and older adults in a mixed lottery choice task. On a subset of trials, we used a color-coding scheme to highlight the saliency of reward probabilities, which served as a decision-aid. The results showed that, in control trials, older adults started to consider probability relative to magnitude information sooner than younger adults, but that their evidence accumulation processes were less sensitive to reward probabilities than that of younger adults. This may indicate a noisier and more stochastic information accumulation process during value-based decisions in old age. The decision-aid increased the influence of probability information on evidence accumulation rates in both age groups, but did not alter the relative timing of accumulation for probability versus magnitude in either group.

Effects and mechanisms of information saliency in enhancing value-based decision-making in younger and older adults.

Aging attenuates frontostriatal network functioning, which could lead to deficits in value computation when decision-making involves uncertainty. Although it has been shown that visually enhancing information saliency of outcome probability can improve decision-making in old age, mechanisms of this effect are still unclear. In the present study, the saliency of outcome probability was increased using a color-coding scheme as a decision aid in a mixed lottery choice task, and spontaneous eye-blink rate and pupillary responses were assessed in younger and older adults. Older adults showed lower value sensitivity than younger adults; however, increasing information saliency benefitted choice behaviors in both age groups. Furthermore, the decision aid reduced pupil size during decision-making in both age groups, suggesting that enhancing information saliency decreases cognitive demands of value computation. Baseline value sensitivity was negatively correlated with benefit of enhancing information saliency only in older adults. As value representations in older decision makers are less distinctive at baseline, they may have required more environmental compensation than younger adults.

Hospitalizations among adults with chronic kidney disease in the United States: A cohort study.

BACKGROUND: Adults with chronic kidney disease (CKD) are hospitalized more frequently than those without CKD, but the magnitude of this excess morbidity and the factors associated with hospitalizations are not well known. METHODS AND FINDINGS: Data from 3,939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2008 at 7 clinical centers in the United States were used to estimate primary causes of hospitalizations, hospitalization rates, and baseline participant factors associated with all-cause, cardiovascular, and non-cardiovascular hospitalizations during a median follow up of 9.6 years. Multivariable-adjusted Poisson regression was used to identify factors associated with hospitalization rates, including demographics, blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria. Hospitalization rates in CRIC were compared with rates in the Nationwide Inpatient Sample (NIS) from 2012. Of the 3,939 CRIC participants, 45.1% were female, and 41.9% identified as non-Hispanic black, with a mean age of 57.7 years, and the mean eGFR is 44.9 ml/min/1.73m2. CRIC participants had an unadjusted overall hospitalization rate of 35.0 per 100 person-years (PY) [95% CI: 34.3 to 35.6] and 11.1 per 100 PY [95% CI: 10.8 to 11.5] for cardiovascular-related causes. All-cause, non-cardiovascular, and cardiovascular hospitalizations were associated with older age (≥65 versus 45 to 64 years), more proteinuria (≥150 to <500 versus <150 mg/g), higher systolic blood pressure (≥140 versus 120 to <130 mmHg), diabetes (versus no diabetes), and lower eGFR (<60 versus ≥60 ml/min/1.73m2). Non-Hispanic black (versus non-Hispanic white) race/ethnicity was associated with higher risk for cardiovascular hospitalization [rate ratio (RR) 1.25, 95% CI: 1.16 to 1.35, p-value < 0.001], while risk among females was lower [RR 0.89, 95% CI: 0.83 to 0.96, p-value = 0.002]. Rates of cardiovascular hospitalizations were higher among those with ≥500 mg/g of proteinuria irrespective of eGFR. The most common causes of hospitalization were related to cardiovascular (31.8%), genitourinary (8.7%), digestive (8.3%), endocrine, nutritional or metabolic (8.3%), and respiratory (6.7%) causes. Hospitalization rates were higher in CRIC than the NIS, except for non-cardiovascular hospitalizations among individuals aged >65 years. Limitations of the study include possible misclassification by diagnostic codes, residual confounding, and potential bias from healthy volunteer effect due to its observational nature. CONCLUSIONS: In this study, we observed that adults with CKD had a higher hospitalization rate than the general population that is hospitalized, and even moderate reductions in kidney function were associated with elevated rates of hospitalization. Causes of hospitalization were predominantly related to cardiovascular disease, but other causes contributed, particularly, genitourinary, digestive, and endocrine, nutritional, and metabolic illnesses. High levels of proteinuria were observed to have the largest association with hospitalizations across a wide range of kidney function levels.

Association of Opioids and Nonsteroidal Anti-inflammatory Drugs With Outcomes in CKD: Findings From the CRIC (Chronic Renal Insufficiency Cohort) Study.

RATIONALE & OBJECTIVE: Safe analgesic choices are limited in chronic kidney disease (CKD). We conducted a comparative analysis of harm from opioids versus nonsteroidal anti-inflammatory drugs (NSAIDs) in CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 3,939 patients with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURES: 30-day analgesic use reported at annual visits. OUTCOMES: A composite outcome of 50% glomerular filtration rate reduction and kidney failure requiring kidney replacement therapy (KRT), as well as the outcomes of kidney failure requiring KRT, hospitalization, and pre-kidney failure death. ANALYTICAL APPROACH: Marginal structural models with time-updated exposures. RESULTS: Participants were followed up for a median of 6.84 years, with 391 (9.9%) and 612 (15.5%) reporting baseline opioid and NSAID use, respectively. Time-updated opioid use was associated with the kidney disease composite outcome, kidney failure with KRT, death (HRs of 1.4 [95% CI, 1.2-1.7], 1.4 [95% CI, 1.1-1.7], and 1.5 [95% CI, 1.2-2.0], respectively), and hospitalization (rate ratio [RR], 1.7; 95% CI, 1.6-1.9) versus opioid nonusers. Similar results were found in an analysis restricted to a subcohort of participants reporting ever using other (nonopioid and non-NSAID) analgesics or tramadol. Time-updated NSAID use was associated with increased risk for the kidney disease composite (HR, 1.2; 95% CI, 1.0-1.5) and hospitalization (RR, 1.1; 95% CI, 1.0-1.3); however, these associations were not significant in the subcohort. The association of NSAID use with the kidney disease composite outcome varied by race, with a significant risk in blacks (HR, 1.3; 95% CI, 1.0-1.7). NSAID use was associated with lower risk for kidney failure with KRT in women and individuals with glomerular filtration rate<45mL/min/1.73m2 (HRs of 0.63 [95% CI, 0.45-0.88] and 0.77 [95% CI, 0.59-0.99], respectively). LIMITATIONS: Limited periods of recall of analgesic use and potential confounding by indication. CONCLUSIONS: Opioid use had a stronger association with adverse events than NSAIDs, with the latter's association with kidney disease outcomes limited to specific subgroups, notably those of black race.

Hyaluronan Induces a Mitochondrial Functional Switch in Fast-Proliferating Human Mesenchymal Stem Cells

Background and Objectives@#Hyaluronan preserves the proliferation and differentiation potential of mesenchymal stem cells. Supplementation of low-concentration hyaluronan (SHA) in stem cells culture medium increases its proliferative rate, whereas coated-surface hyaluronan (CHA) maintains cells in a slow-proliferating mode. We have previously demonstrated that in CHA, the metabolic proliferative state of stem cells was influenced by upregulating mitochondrial biogenesis and function. However, the effect of SHA on stem cells’ energetic status remains unknown. In this study, we demonstrate the effect that low-concentration SHA at 0.001 mg/ml (SHA0.001) and high-concentration SHA at 5 mg/ml (SHA5) exert on stem cells’ mitochondrial function compared with CHA and noncoated tissue culture surface (control). @*Methods@#and Results: Fast-proliferating human placenta-derived mesenchymal stem cells (PDMSCs) cultured on SHA0.001 exhibited reduced mitochondrial mass, lower mitochondrial DNA copy number, and lower oxygen consumption rate compared with slow-proliferating PDMSCs cultured on CHA at 5.0 (CHA5) or 30 μg/cm2 (CHA30). The reduced mitochondrial biogenesis observed in SHA0.001 was accompanied by a 2-fold increased ATP content and lactate production, suggesting that hyaluronan-induced fast-proliferating PDMSCs may rely less on mitochondrial function as an energy source and induce a mitochondrial functional switch to glycolysis. @*Conclusions@#PDMSCs cultured on both CHA and SHA exhibited a reduction in reactive oxygen species levels. The results from this study clarify our understandings on the effect of hyaluronan on stem cells and provide important insights into the effect of distinct supplementation methods used during cell therapies.

Interactive effects of dopamine transporter genotype and aging on resting-state functional networks.

Aging and dopamine modulation have both been independently shown to influence the functional connectivity of brain networks during rest. Dopamine modulation is known to decline during the course of aging. Previous evidence also shows that the dopamine transporter gene (DAT1) influences the re-uptake of dopamine and the anyA9 genotype of this gene is associated with higher striatal dopamine signaling. Expanding these two lines of prior research, we investigated potential interactive effects between aging and individual variations in the DAT1 gene on the modular organization of brain acvitiy during rest. The graph-theoretic metrics of modularity, betweenness centrality and participation coefficient were assessed in 41 younger (age 20-30 years) and 37 older (age 60-75 years) adults. Age differences were only observed in the participation coefficient in carriers of the anyA9 genotype of the DAT1 gene and this effect was most prominently observed in the default mode network. Furthermore, we found that individual differences in the values of the participation coefficient correlated with individual differences in fluid intelligence and a measure of executive control in the anyA9 carriers. The correlation between participation coefficient and fluid intelligence was mainly shared with age-related differences, whereas the correlation with executive control was independent of age. These findings suggest that DAT1 genotype moderates age differences in the functional integration of brain networks as well as the relation between network characteristics and cognitive abilities.

Inflammation and Apparent Treatment-Resistant Hypertension in Patients With Chronic Kidney Disease.

Apparent treatment-resistant hypertension (ATRH) is highly prevalent and associated with cardiovascular disease risk in patients with chronic kidney disease. We analyzed the association of inflammatory biomarkers with ATRH and its complications in patients with chronic kidney disease. ATRH was defined as blood pressure ≥140/90 mm Hg while taking ≥3 antihypertensive medications or blood pressure <140/90 mm Hg while taking ≥4 medications. Analyses included 1359 CRIC study (Chronic Renal Insufficiency Cohort) participants with ATRH and 2008 hypertensive participants without. Logistic regression was used to examine cross-sectional associations of inflammatory biomarkers and ATRH adjusting for demographic, lifestyle, and clinical risk factors and treatments. Cox proportional hazards models were used to assess the impact of inflammatory biomarkers on associations of ATRH with composite cardiovascular disease and mortality beyond conventional risk factors. Multivariable-adjusted odds ratio (95% CI) of ATRH for the highest tertile versus the lowest tertile of inflammatory biomarker levels was 1.29 (95% CI, 1.05-1.59) for IL (interleukin)-6, 1.49 (95% CI, 1.20-1.85) for TNF-α (tumor necrosis factor-α), and 0.77 (95% CI, 0.63-0.95) for TGF-ß (transforming growth factor-ß). High-sensitivity CRP (C-reactive protein), fibrinogen, IL-1ß, and IL-1 receptor antagonist were not significantly associated with ATRH. Adding inflammatory biomarkers to Cox models did not attenuate the significant association of ATRH with cardiovascular disease and mortality. Our findings show higher levels of IL-6 and TNF-α and lower levels of TGF-ß were independently associated with odds of ATRH. Targeting specific inflammatory pathways may improve blood pressure control in patients with chronic kidney disease.

Modeling the impact of obesity on the lifetime risk of chronic kidney disease in the United States using updated estimates of GFR progression from the CRIC study.

RATIONALE & OBJECTIVE: As the prevalence of obesity continues to rise in the United States, it is important to understand its impact on the lifetime risk of chronic kidney disease (CKD). STUDY DESIGN: The CKD Health Policy Model was used to simulate the lifetime risk of CKD for those with and without obesity at baseline. Model structure was updated for glomerular filtration rate (GFR) decline to incorporate new longitudinal data from the Chronic Renal Insufficiency Cohort (CRIC) study. SETTING AND POPULATION: The updated model was populated with a nationally representative cohort from National Health and Nutrition Examination Survey (NHANES). OUTCOMES: Lifetime risk of CKD, highest stage and any stage. MODEL, PERSPECTIVE, & TIMEFRAME: Simulation model following up individuals from current age through death or age 90 years. RESULTS: Lifetime risk of any CKD stage was 32.5% (95% CI 28.6%-36.3%) for persons with normal weight, 37.6% (95% CI 33.5%-41.7%) for persons who were overweight, and 41.0% (95% CI 36.7%-45.3%) for persons with obesity at baseline. The difference between persons with normal weight and persons with obesity at baseline was statistically significant (p<0.01). Lifetime risk of CKD stages 4 and 5 was higher for persons with obesity at baseline (Stage 4: 2.1%, 95% CI 0.9%-3.3%; stage 5: 0.6%, 95% CI 0.0%-1.1%), but the differences were not statistically significant (stage 4: p = 0.08; stage 5: p = 0.23). LIMITATIONS: Due to limited data, our simulation model estimates are based on assumptions about the causal pathways from obesity to CKD, diabetes, and hypertension. CONCLUSIONS: The results of this study indicate that obesity may have a large impact on the lifetime risk of CKD. This is important information for policymakers seeking to set priorities and targets for CKD prevention and treatment.

Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

BACKGROUND: Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study. METHODS: Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance. RESULTS: Hematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models. CONCLUSION: In a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction.

Evolution of Echocardiographic Measures of Cardiac Disease From CKD to ESRD and Risk of All-Cause Mortality: Findings From the CRIC Study.

RATIONALE & OBJECTIVE: Abnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality. STUDY DESIGN: Prospective study. SETTING & PARTICIPANTS: We studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD. PREDICTOR: We measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD. OUTCOMES: All-cause mortality after dialysis therapy initiation. ANALYTICAL APPROACH: Cox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality. RESULTS: Over a mean of 2.9 years between pre- and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P<0.001) and LVESV (18.6 to 20.2mL/m2.7; P<0.001). During this time, there was improvement in left ventricular mass index (60.4 to 58.4g/m2.7; P=0.005) and diastolic relaxation (11.11% to 4.94% with moderately/severely abnormal; P=0.02). Changes in left atrial volume (4.09 to 4.15mL/m2; P=0.08) or LVEDV (38.6 to 38.4mL/m2.7; P=0.8) were not significant. Worsening from CKD to ESRD of LVEF (adjusted HR for every 1% decline in LVEF, 1.03; 95% CI, 1.00-1.06) and LVESV (adjusted HR for every 1mL/m2.7 increase, 1.04; 95% CI, 1.02-1.07) were independently associated with greater risk for postdialysis mortality. LIMITATIONS: Some missing or technically inadequate echocardiograms. CONCLUSIONS: In a longitudinal study of patients with CKD who subsequently initiated dialysis therapy, LVEF and LVESV worsened and were significantly associated with greater risk for postdialysis mortality. There may be opportunities for intervention during this transition period to improve outcomes.

Left centro-parieto-temporal response to tool-gesture incongruity: an ERP study.

BACKGROUND: Action semantics have been investigated in relation to context violation but remain less examined in relation to the meaning of gestures. In the present study, we examined tool-gesture incongruity by event-related potentials (ERPs) and hypothesized that the component N400, a neural index which has been widely used in both linguistic and action semantic congruence, is significant for conditions of incongruence. METHODS: Twenty participants performed a tool-gesture judgment task, in which they were asked to judge whether the tool-gesture pairs were correct or incorrect, for the purpose of conveying functional expression of the tools. Online electroencephalograms and behavioral performances (the accuracy rate and reaction time) were recorded. RESULTS: The ERP analysis showed a left centro-parieto-temporal N300 effect (220-360 ms) for the correct condition. However, the expected N400 (400-550 ms) could not be differentiated between correct/incorrect conditions. After 700 ms, a prominent late negative complex for the correct condition was also found in the left centro-parieto-temporal area. CONCLUSIONS: The neurophysiological findings indicated that the left centro-parieto-temporal area is the predominant region contributing to neural processing for tool-gesture incongruity in right-handers. The temporal dynamics of tool-gesture incongruity are: (1) firstly enhanced for recognizable tool-gesture using patterns, (2) and require a secondary reanalysis for further examination of the highly complicated visual structures of gestures and tools. The evidence from the tool-gesture incongruity indicated altered brain activities attributable to the N400 in relation to lexical and action semantics. The online interaction between gesture and tool processing provided minimal context violation or anticipation effect, which may explain the missing N400.

Menstrual Cycle Hormone Changes in Women Traversing Menopause: Study of Women's Health Across the Nation.

Context: Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. Objective: To describe day-to-day menstrual cycle hormones in women as they approach menopause from the Study of Women's Health Across the Nation Daily Hormone Study (DHS). Design: DHS enrollees collected daily urine for one entire menstrual cycle or up to 50 days, whichever came first, annually, up to the final menstrual period (FMP) or for up to 10 years. Setting: Seven sites across the United States. Participants: A total of 511 premenopausal or early perimenopausal women at enrollment, within 10 years before menopause. Intervention: Time-to-FMP measurement. Main Outcome Measures: Evidence of luteal activity (ELA), determined using objective algorithms. Menstrual cycle/segment length; whole cycle, and segment integrated urinary luteinizing hormone, follicle-stimulating hormone, estrone conjugates, and pregnanediol glucuronide (Pdg) for each year, organized around the FMP. Results: Mean menstrual cycle length was remarkably preserved at 26 to 27 days in ELA cycles; non-ELA cycles had greater variability. The percentage of cycles that were ELA remained high until 5 years before the FMP (87.9%); only 22.8% of cycles within 1 year of the FMP were ELA. Whole cycle hormones remained relatively stable up to 3 years before the FMP, when gonadotropins began to increase. Pdg excretion declined slowly with progress to the FMP, but Pdg patterns of ELA cycles remained distinguishable from non-ELA. Conclusions: Menstrual cycle hormone patterns in perimenopausal women resemble those of midreproductive-aged women until 5 years before menopause, and presumably ovulatory cycles retain a potentially fertile pattern up to the end of reproductive life.

Functional and anatomical dissociation between the orthographic lexicon and the orthographic buffer revealed in reading and writing Chinese characters by fMRI.

The contribution of orthographic representations to reading and writing has been intensively investigated in the literature. However, the distinction between neuronal correlates of the orthographic lexicon and the orthographic (graphemic) buffer has rarely been examined in alphabetic languages and never been explored in non-alphabetic languages. To determine whether the neural networks associated with the orthographic lexicon and buffer of logographic materials are comparable to those reported in the literature, the present fMRI experiment manipulated frequency and the stroke number of Chinese characters in the tasks of form judgment and stroke judgment, which emphasized the processing of character recognition and writing, respectively. It was found that the left fusiform gyrus exhibited higher activation when encountering low-frequency than high-frequency characters in both tasks, which suggested this region to be the locus of the orthographic lexicon that represents the knowledge of character forms. On the other hand, the activations in the posterior part of the left middle frontal gyrus and in the left angular gyrus were parametrically modulated by the stroke number of target characters only in the stroke judgment task, which suggested these regions to be the locus of the orthographic buffer that represents the processing of stroke sequence in writing. These results provide the first evidence for the functional and anatomical dissociation between the orthographic lexicon and buffer in reading and writing Chinese characters. They also demonstrate the critical roles of the left fusiform area and the frontoparietal network to the long-term and short-term representations of orthographic knowledge, respectively, across different orthographies.

Trajectories of Vasomotor Symptoms and Carotid Intima Media Thickness in the Study of Women's Health Across the Nation.

BACKGROUND AND PURPOSE: Emerging work has linked menopausal vasomotor symptoms (VMS) to subclinical cardiovascular disease (CVD) among women. However, VMS are dynamic over time. No studies have considered how temporal patterns of VMS may relate to subclinical CVD. We tested how temporal patterns of VMS assessed over 13 years were related to carotid intima media thickness (IMT) among midlife women. METHODS: The Study of Women's Health Across the Nation is a longitudinal cohort study of midlife women. Eight hundred and eleven white, black, Hispanic, and Chinese participants with a well-characterized final menstrual period completed measures of VMS, a blood draw, and physical measures approximately annually for 13 years. Women underwent a carotid artery ultrasound at study visit 12. RESULTS: Four trajectories of VMS were identified by trajectory analysis (consistently high, early-onset, late-onset, persistently low VMS) and tested in relation to carotid indices in linear regression models. Results indicated that women with early-onset VMS had both greater mean IMT (beta, b [standard error, SE]=0.03 [0.01], P=0.03) and greater maximal IMT (b [SE]=0.04 [0.01], P=0.008) than women with consistently low VMS, adjusting for demographics and CVD risk factors. CONCLUSIONS: This is the first study to test trajectories of VMS in relation to subclinical CVD. Women with VMS early in the menopause transition had higher mean IMT and maximal IMT than those with consistently low VMS across the transition. Associations were not accounted for by demographic factors nor by CVD risk factors. Results can signal to women in need of early CVD risk reduction.

Trajectories of estradiol and follicle-stimulating hormone over the menopause transition and early markers of atherosclerosis after menopause.

AIM: The purpose of this study was to assess associations between distinct patterns of circulating estradiol (E2) and follicle-stimulating hormone (FSH) over the menopause transition (MT) and subclinical measures of atherosclerosis after menopause. METHODS AND RESULTS: Four temporal patterns of E2 decline (Low: low before and after final menstrual period (FMP); Medium: medium before and high after FMP; High-early decline: high prior to FMP and early decline thereafter; High-late decline: high prior to FMP and late decline thereafter) and three of FSH rise (Low, Medium, High) over 9.6 years across FMP were identified and linked to carotid intima-media-thickness (IMT), adventitial diameter (AD), and presence of carotid plaque (cPlaque) measured after menopause at the 12th annual visit (visit 12). Participants were 856 women (age at visit 12 = 59.5 ± 2.7 years) from the Study of Women's Health Across the Nation (SWAN), who never reported a stroke or a heart attack. In models adjusted for visit 12 or baseline cardiovascular disease (CVD) risk factors, odds of having any cPlaque were ∼43% lower among women with the High-early decline E2 trajectory compared to women with the Low E2 trajectory. In contrast, women with the Medium E2 trajectory had significantly higher IMT than those with the Low E2 trajectory adjusting for visit 12 CVD risk factors. Interestingly, adjusting for baseline CVD risk factors attenuated this association. The Low FSH group had lower IMT than the Medium and High FSH groups (p ≤ 0.05) in all models. CONCLUSION: During MT, women are subjected to hormonal alterations that could potentially increase their risk of developing CVD after menopause.