Cognitive Reserve and Cognitive Functioning among Oldest Old Adults: Findings from the Georgia Centenarian Study.

OBJECTIVES: Living a long life does not guarantee the maintenance of optimal cognitive functioning; however, similar to older adults in general, cognitive reserve may also protect oldest-old adults from cognitive decline. The purpose of this study was to assess cognitive reserve among centenarians and octogenarians and to evaluate a process model of cognitive reserve. METHODS: A total of 321 centenarians and octogenarians from the Georgia Centenarian Study were included in this study. Cognitive reserve components included level of education, occupational responsibility, current social engagement, past engaged lifestyle, and activity. Cognitive functioning was measured with the Mini-Mental Status Examination. RESULTS: Structural equation modeling was computed, and the overall model fit well, χ2 (df = 3) = 5.02, p = .17; CFI = .99, RMSEA = .05. Education is directly and indirectly related to cognitive functioning through occupational responsibility and past engaged lifestyle. Current social engagement is related to cognitive functioning directly and indirectly through current activities. The four direct predictors (i.e., education, current social engagement, current activity, and past engaged lifestyle) explained 35% of the variance in cognitive functioning. CONCLUSION: The results provide important information for cognitive reserve theories with implications for interventions that build cognitive reserve.

Exercise, diet, and sleep habits of nurses working full-time during the COVID-19 pandemic: An observational study.

BACKGROUND: Healthy diet, exercise, and sleep practices may mitigate stress and prevent illness. However, lifestyle behaviors of acute care nurses working during stressful COVID-19 surges are unclear. PURPOSE: To quantify sleep, diet, and exercise practices of 12-hour acute care nurses working day or night shift during COVID-19-related surges. METHODS: Nurses across 10 hospitals in the United States wore wrist actigraphs and pedometers to quantify sleep and steps and completed electronic diaries documenting diet over 7-days. FINDINGS: Participant average sleep quantity did not meet national recommendations; night shift nurses (n = 23) slept significantly less before on-duty days when compared to day shift nurses (n = 34). Proportionally more night shift nurses did not meet daily step recommendations. Diet quality was low on average among participants. DISCUSSION: Nurses, especially those on night shift, may require resources to support healthy sleep hygiene, physical activity practices, and diet quality to mitigate stressful work environments.

Better Social-emotional Behavior in Young Nepali Children is Associated with Household Wealth, Child Age, and Family Participation in a Community Development Intervention.

Background Mental health and behavior problems are under-recognized in low- and middleincome countries, especially in young children. Early identification of these problems could encourage governments to address the shortages of child mental health professionals and promote early intervention programs to help children achieve their full developmental potential. Objective Describe the social-emotional development of young rural Nepali children; explore risk factors for poor development. Method The study was embedded in a longitudinal intervention trial comparing control households with those who received training in family nutrition+livestock management (Partial Package) or family nutrition+livestock management+community mobilization (Full Package). At midline, enumerators completed a 145-item household questionnaire, child anthropometry, and Administered the Ages and Stages Questionnaire-Social-Emotional (ASQ-SE) to all enrolled children age 33-47 months (n=310). Bivariate and regression analyses examined the relationship of child and household risk factors to administered the Ages and Stages QuestionnaireSocial-Emotional scores. Result Administered the Ages and Stages Questionnaire-Social-Emotional scores were below age cutoffs in 24% of children, suggesting worse social-emotional development. In bivariate analyses and the adjusted linear regression model, older child age, greater household wealth, and Full Package Intervention status were all associated with better social-emotional development scores. Partial Package Intervention status was associated with worse scores. Conclusion The Administered the Ages and Stages Questionnaire-Social-Emotional is a potential tool to assess child social-emotional development in the context of household and community level interventions. Further work is necessary to validate the administered the Ages and Stages Questionnaire-Social-Emotional and similar tools in Nepal, and to better understand the prevalence of challenges to optimal socialemotional development in young children in order to use this information to design and monitor needed interventions.

Direct, Indirect, and Combined Extracranial-to-Intracranial Bypass for Adult Moyamoya Disease: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Moyamoya disease is a chronic, progressive cerebrovascular disease involving occlusion or stenosis of the terminal portion of the internal carotid artery. We conducted an updated systematic review and meta-analysis to investigate clinical and angiographic outcomes comparing direct, combined, and indirect bypass for the treatment of moyamoya disease in adults. METHODS: Two independent authors performed Preferred Reporting Items for Systematic reviews and Meta-Analyses guided literature searches in December 2021 to identify articles reporting clinical/angiographic outcomes in adult moyamoya disease patients undergoing bypass. Primary end points used were ischemic and hemorrhagic strokes, clinical outcomes, and angiographic revascularization. Study quality was evaluated with Newcastle-Ottawa and the Oxford Center for Evidence-Based Medicine scales. RESULTS: Four thousand four hundred fifty seven articles were identified in the initial search; 143 articles were analyzed. There were 3827 direct, 3826 indirect, and 3801 combined bypasses. Average length of follow-up was 3.59±2.93 years. Pooled analysis significantly favored direct (odds ratio [OR], 0.62 [0.48-0.79]; P<0.0001; OR, 0.44 [0.32-0.59]; P<0.0001; OR, 0.56 [0.42-0.74]; P<0.0001; OR, 3.1 [2.5-3.8]; P=0.0001) and combined (OR, 0.53 [0.41-0.69]; P<0.0001; OR, 0.28 [0.2-0.41]; P<0.0001; OR, 0.41 [0.3-0.56]; P<0.0001; OR, 3.1 [2.8-4.3]; P=0.0001) over indirect bypass for early stroke, late stroke, late intracerebral hemorrhage, and favorable outcomes, respectively. Indirect bypass was favored over combined (OR, 3.1 [1.7-5.6]; P<0.0001) and direct (OR, 4.12 [2.34-7.25]; P<0.0001) for early intracerebral hemorrhage. The meta-analysis significantly favored direct (OR, 0.37 [0.23-0.60]; P<0.001; OR, 0.49 [0.31-0.77]; P=0.002) and combined (OR, 0.23 [0.12-0.43]; P<0.00001; OR, 0.30 [0.18-0.49]; P<0.00001) bypass over indirect bypass for late stroke and late hemorrhage, respectively. Combined bypass was favored over indirect bypass for favorable outcomes (OR, 2.06 [1.18-3.58]; P=0.01). CONCLUSIONS: Based on combined meta-analysis (43 articles) and pooled analysis (143 articles), the existing literature indicates that combined and direct bypasses have significant benefits for patients suffering from late stroke and hemorrhage versus indirect bypass. Combined bypass was favored over indirect bypass for favorable outcomes. This is a strong recommendation based on low-quality evidence when utilizing the Grades of Recommendation, Assessment, Development, and Evaluation system. These findings have important implications for bypass strategy selection.

Frailty and Cognitive Function in Older Adults: A Systematic Review and Meta-Analysis of Cross-Sectional Studies.

The relationship between cognitive function and frailty among older adults is a growing area of research due to the implications of cognitive and physical decline for functional independence in late life. Multiple studies demonstrate a meaningful relationship between these two factors, which together may constitute increased risk of negative health outcomes for older adults. The current analysis was conducted to 1) systematically review current evidence for differences in cognitive performance based on frailty status among older adults and provide quantitative evidence for the magnitude of this effect, and 2) assess the influence of demographic and methodological variables on this effect. The preregistered protocol (CRD42018087138) included a search of EBSCOhost, Pubmed, and Embase online databases and reference lists to identify cross-sectional studies comparing frail and non-frail or robust older adults (60+) on cognitive performance. In total, 42 effects were retrieved from 38 studies, expressed as Hedges' g, and pooled based on a random-effects model. Results indicated an overall significant, negative effect of frailty status on cognitive function among tests of global cognitive function (g = 0.734: 95% CI = 0.601-0.867) and individual cognitive domains (g = 0.439: 95% CI = 0.342-0.535). Age, frailty assessment used, and cognitive status of the sample did not significantly moderate the overall effect. Post-hoc moderator analysis revealed that difference in mean age of frail and robust groups significantly moderated the overall effect (R2 = 0.38, ß = .0974, 95% CI = 0.0537-0.141). Implications for future research are discussed.

Women's Perceptions of HIV- and Sexuality-Related Stigma in Relation to PrEP: Qualitative Findings from the Masibambane Study, Durban, South Africa.

Daily oral pre-exposure prophylaxis (PrEP) offers effective HIV prevention. In South Africa, PrEP is publicly available, but use among young women remains low. We explored young women's perceptions of PrEP to inform a gender-focused intervention to promote PrEP uptake. Six focus group discussions and eight in-depth interviews exploring perceptions of PrEP were conducted with forty-six women not using PrEP, ages 18-25, from central Durban. Data were thematically analyzed using a team-based consensus approach. The study was conducted among likely PrEP users: women were highly-educated, with 84.8% enrolled in post-secondary education. Qualitative data revealed intersecting social stigmas related to HIV and women's sexuality. Women feared that daily PrEP pills would be confused with anti-retroviral treatment, creating vulnerability to misplaced HIV stigma. Women also anticipated that taking PrEP could expose them to assumptions of promiscuity from the community. To address these anticipated community-level reactions, women suggested community-facing interventions to reduce the burden on young women considering PrEP. Concerns around PrEP use in this group of urban, educated women reflects layered stigmas that may inhibit future PrEP use. Stigma-reducing strategies, such as media campaigns and educational interventions directed at communities who could benefit from PrEP, should re-frame PrEP as an empowering and responsible choice for young women.

Planktos: An Agent-Based Modeling Framework for Small Organism Movement and Dispersal in a Fluid Environment with Immersed Structures.

Multiscale modeling of marine and aerial plankton has traditionally been difficult to address holistically due to the challenge of resolving individual locomotion dynamics while being carried with larger-scale flows. However, such problems are of paramount importance, e.g., dispersal of marine larval plankton is critical for the health of coral reefs, and aerial plankton (tiny arthropods) can be used as effective agricultural biocontrol agents. Here we introduce the open-source, agent-based modeling software Planktos targeted at 2D and 3D fluid environments in Python. Agents in this modeling framework are relatively tiny organisms in sufficiently low densities that their effect on the surrounding fluid motion can be considered negligible. This library can be used for scientific exploration and quantification of collective and emergent behavior, including interaction with immersed structures. In this paper, we detail the implementation and functionality of the library along with some illustrative examples. Functionality includes arbitrary agent behavior obeying either ordinary differential equations, stochastic differential equations, or coded movement algorithms, all under the influence of time-dependent fluid velocity fields generated by computational fluid dynamics, experiments, or analytical models in domains with static immersed mesh structures with sliding or sticky collisions. In addition, data visualization tools provide images or animations with kernel density estimation and velocity field analysis with respect to deterministic agent behavior via the finite-time Lyapunov exponent.

Development and Validation of Robust and Cost-Effective Liquid Heterogeneous Phantom for Time Domain Near-Infrared Optical Tomography.

Diffused light imaging techniques, such as near-infrared optical tomography (NIROT), require a stable platform for testing and validation that imitates tissue optical properties. The aim of this work was to build a robust, but flexible liquid phantom for BORL time-domain NIROT system Pioneer. The phantom was designed to assess penetration depth and resolution of the system, and to provide a heterogeneous inner structure that can be changed in controllable manner with adjustable optical properties. We used only in-house produced 3D-printed elements and mechanics of a budget 3D-printer to build the phantom, and managed to keep the overall costs below $500. We achieved stable and repeatable movement of an arbitrary structure in 3+1 degree of freedom inside the phantom and demonstrated its performance in a series of tests. Thus, we presented a universal and cost-effective solution for testing NIROT, that can be easily customised to various systems or testing paradigms.

Pre-Morbid IQ Moderates the Relationship between Cognitive Performance and Performance-Based Functional Status in Older Adults.

Objectives: The current study sought to evaluate the relationship between cognitive performance and Instrumental Activities of Daily Living (IADL) performance in a population of community dwelling older adults, and assess to what extent this relationship is moderated by cognitive reserve (Premorbid-IQ)Methods: 123 community-dwelling older adults completed a general cognitive assessment, a word-reading based premorbid-IQ estimate (PMIQE) measure, and the performance-based Direct Assessment of Functional Status, Revised (DAFS-R). Moderated regression analysis was used to assess the influence of PMIQE on the relationship between cognitive performance and IADLs.Results: There was a significant main effect of cognitive performance on IADLs, and no main effect of PMIQE on functional IADLs. There was a significant moderating effect of PMIQE on the relationship between cognitive performance and IADLs performance, such that at higher levels of PMIQE, cognitive performance scores became slightly less predictive of weaknesses in IADLs.Conclusions: Results suggest that for individuals with high reserve, assessment of cognitive performance alone may not be robust a predictor of IADLs functioning.Clinical implications: In estimating functional abilities as a consequence of cognitive performance, consideration should be given to premorbid-IQ/cognitive reserve.

High Recreational Gamblers Show Increased Stimulatory Effects of an Acute Laboratory Gambling Challenge.

Gambling in moderation is a socially acceptable behavior and over 60% of the Swedish population gambles every year. It has been seen that slot machines are one of the most addictive and problematic forms of gambling and contribute highly to an addictive behavior. It is unclear why some individuals intensify their gambling behavior over time to extreme levels while others do not. Initial positive response of a drug or as in this case a gambling behavior, most likely influences the likelihood of continuing use in non-addicted individuals. Therefore, we wanted to investigate if recreational gamblers show an altered subjective response to an online gambling challenge, e.g. to casino gambling. The present study was designed to examine the subjective effects after an acute gambling challenge, in healthy recreational gamblers compared with non-gamblers. Eighty-two subjects participated in the study. They were challenged with an acute online slot machine gambling challenge and self-report questionnaires of mood and blood pressure were taken before and after gambling. The gamblers, and more specifically the high recreational gamblers, reported increased stimulative effects after the gambling challenge in comparison to the non-gamblers. Findings suggests that gamblers experience significantly higher arousal effects to an acute online slot machine challenge. This response may be a uniquely predictive behavior for increased risk of gambling addiction.

The Influence of Socioeconomic Status and Academic Standing on Concussion-Reporting Intentions and Behaviors in Collegiate Athletes.

Concussion education have served as a keystone for improving concussion reporting. Numerous factors affecting concussion reporting have been explored; however, the role of socioeconomic status (SES) in reporting has not been established. We examined the influence of SES and academic achievement (high-school grade point average [HS-GPA] and American College Testing [ACT] composite scores) on athletes' concussion-reporting intentions and behaviors. A cross-sectional study was employed among 191 athletes (94 female; age 19.3 ± 1.2 years). Athletes reported SES metrics (parental education and occupation, household income, HS-GPA, and ACT composite score) prior to their athletic season and completed a survey assessing symptom- and concussion-reporting intentions. Symptom- and concussion-reporting behaviors were assessed among athletes who experienced a concussion within the past year. SES was determined using the Hollingshead Four-Factor Index grouping athletes into SES strata. Athletes were grouped into low/high categories for academic achievement and household income variables. The 191 athletes were included for symptom- and concussion-reporting intentions analyses, while 46 and 41 were included for symptom- and concussion-reporting behavior, respectively. Nonparametric statistics with false discovery rate adjusted p values were employed. We found symptom- and concussion-reporting intentions, and symptom- and concussion-reporting behaviors were not significantly different based on SES strata (all p values ≥.64), household income (all p values ≥.64), HS-GPA (all p values ≥.24), or ACT scores (all p values ≥.25). Overall, SES and academic achievement may not play a role in understanding concussion reporting among middle- to high-SES collegiate athletes. Implementing policies targeting certain SES and academic levels might be an ineffective health care strategy for increasing reporting.

Nucleophilic Activation of Red Phosphorus for Controlled Synthesis of Polyphosphides.

Reactions between red phosphorus (Pred) and potassium ethoxide in various organic solvents under reflux convert this rather inert form of the element to soluble polyphosphides. The activation is hypothesized to proceed via a nucleophilic attack by ethoxide on the polymeric structure of Pred, leading to disproportionation of the latter, as judged from observation of P(OEt)3 in the reaction products. A range of solvents has been probed, revealing that different polyphosphide anions (P73-, P162-, P213-, and P5-) can be stabilized depending on the combination of the boiling point and dielectric constant (polarity) of the solvent. The effectiveness of activation also depends on the nature of nucleophile, with the rate of reaction between Pred and KOR increasing in the order t-Bu < n-Hex < Et < Me, which is in agreement with the increasing order of nucleophilic strength. Thiolates and amides were also examined as potential activators, but the reaction with these nucleophiles were substantially slower; nonetheless, all reactions between Pred and NaSR yielded exclusively P162- as a soluble polyphosphide product.

Sociodemographic factors associated with patients hospitalised for coccidioidomycosis in California and Arizona, State Inpatient Database 2005-2011.

Coccidioidomycosis is endemic in the Southwestern United States. Disseminated infection can be life-threatening and is responsible for hospitalisation and significant healthcare resource utilisation. There are limited data evaluating factors associated with hospitalisation for coccidioidomycosis. We conducted a cross-sectional study to assess incidence and factors associated with coccidioidomycosis-associated hospitalisation in California and Arizona. We analysed hospital discharge data obtained from the State Inpatient Dataset for California and Arizona between 2005 and 2011 and performed multivariable logistic regression examining factors associated with coccidioidomycosis-associated hospitalisation. During our time frame, we found 23 758 coccidioidomycosis-associated hospitalisations. Coccidioidomycosis incidence was over sixfold higher in Arizona compared to California (198.9 vs. 29.6/100 000 person-years). In our multivariable model, coccidioidomycosis-associated hospitalisation was associated with age group 40-49 years (referent group: age 18-29 years, adjusted odds ratio (aOR) = 1.50 (95% confidence interval (CI) 1.43-1.59)), African American race (referent group: Caucasian, aOR = 1.98 (95% CI 1.89-2.06)), residing in a large rural town (referent group: urban area, aOR = 2.28 (95% CI 2.19-2.39)), uncomplicated diabetes (aOR = 1.47 (95% CI 1.41-1.52)) chronic obstructive pulmonary disease (aOR = 1.59 (95% CI 1.54-1.65)) and higher number of comorbidities (aOR = 1.02 (95% CI 1.02-1.03) for each point in the Elixhauser score). Identifying persons at highest risk for hospitalisation with coccidioidomycosis may be helpful for future prevention efforts.

Lessons learned from the development of a hidradenitis suppurativa xenograft mouse model.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease originating from the pilosebaceous unit, in which patients develop painful abscesses, sinus tracts, nodules and scarring, typically in intertriginous areas. Major gaps in our understanding of HS exist, and these may be partially due to the lack of an animal model for experimental studies. We developed an HS xenograft mouse model using human HS lesions grafted onto immunocompromised mice. Although the model had its limitations, several informative lessons were learned, which may contribute to future attempts at an HS animal model.

Repeated Sport-Related Concussion Shows Only Minimal White Matter Differences Many Years After Playing High School Football.

OBJECTIVE: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22-47 years following football retirement) using diffusion tensor imaging (DTI). METHOD: Forty former high school football players aged 40-65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. RESULTS: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p < .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p < .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. DISCUSSION: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.

The use of bacteriophage MS2 for the development and application of a virucide decontamination test method for porous and heavily soiled surfaces.

AIMS: (i) To develop an analytical method for recovery and quantification of bacteriophage MS2-as a surrogate for foot-and-mouth disease virus-from complex porous surfaces, with and without the presence of laboratory-developed agricultural grime; (ii) to evaluate, with a 4-log dynamic range, the virucidal activity of common biocides for their ability to decontaminate surfaces and hence remediate facilities, following a foreign animal disease contamination incident. METHODS AND RESULTS: An analytical method was developed and optimized for MS2 recovery from simulated agricultural surfaces. The addition of Dey-Engley neutralizing broth to an extraction buffer improved MS2 viability in liquid extracts, with optimal analytical holding times determined as <8 to ≤24 h, depending on matrix. The recovery of MS2 from surface materials decreased in the order: nonporous reference material >grimed porous materials >nongrimed porous materials. In disinfectant testing, two spray applications of pAB were effective against MS2 (≥4-log reduction) on all operational-scale materials. Two per cent citric acid had limited effectiveness, with a ≥4-log reduction observed on a selected subset of grimed concrete samples. CONCLUSIONS: Decontamination efficacy test results can be affected by surface characteristics, extraction buffer composition, analytical holding time and surface-specific organism survivability. Efficacy should be evaluated using a test method that reflects the environmental characteristics of the intended application. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study demonstrate the importance of analytical method verification tests for disinfectant testing prior to application in complex environments.

Cardiovascular health and cognitive functioning among centenarians: a comparison between the Tokyo and Georgia centenarian studies.

ABSTRACTObjectives:Centenarians have survived into very late life, but whether they reach very old age in good health remains unclear. The purpose of this study was to compare the cardiovascular health status and cognitive functioning of centenarians in the United States with centenarians in Japan. DESIGN, SETTING, AND PARTICIPANTS: This cross-national design compared centenarians from the United States and Japan. The sample of U.S. centenarians was recruited from the Georgia Centenarian Study and included 287 centenarians. The sample of Japanese centenarians was recruited from the Tokyo Centenarian Study and included 304 centenarians. MEASUREMENTS: Cognitive functioning was assessed with a mental status questionnaire, and cardiovascular disease by a health history assessment, blood pressure, and selected blood parameters. RESULTS: The results suggest that Tokyo centenarians had lower disease experiences and BMI values, when compared to Georgia centenarians, but blood pressure was higher among Japanese centenarians. Lower levels of hemoglobin in Japanese centenarians and higher levels of C-reactive protein in Georgia were also found. The positive association of hypertension and albumin levels with cognitive functioning and the negative association of stroke occurrence with cognitive functioning were replicated in both countries. Differential effects were obtained for heart problems, BMI, and C-reactive protein (with positive effects for Tokyo centenarians, except for C-reactive protein). CONCLUSION: For extremely old individuals, some markers of cardiovascular disease are replicable across countries, whereas differential effects for cardiovascular health also need to be considered in cardiovascular health.

Collegiate student-athlete sex, years of sport eligibility completed, and sport contact level influence on concussion reporting intentions and behaviours.

PRIMARY OBJECTIVE: The objective of this study was to determine whether sex, years of sport eligibility completed, and sport contact level influenced student-athletes' concussion reporting intentions and behaviours. RESEARCH DESIGN: Cross-sectional. METHODS AND PROCEDURES: Student-athletes (n = 828) reported their sex, years of sport eligibility completed, sport, and completed concussion reporting intentions and behaviours surveys. Nonparametric statistics were conducted to compare intentions and behaviours between groups (alpha = 0.05). MAIN OUTCOMES AND RESULTS: Females had higher indirect intentions to report concussion than males (p = 0.035), but did not differ in direct intentions (p = 0.258) or behaviours (indirect: p = 0.756; direct: p = 0.686). Intentions (indirect: p = 0.383; direct: p = 0.397) and behaviours (indirect: p = 0.154; direct: p = 0.999) did not differ between years of sport eligibility completed. Limited/non-contact sport student-athletes intended to report more concussions than those in collision/contact sports (indirect: p = 0.001; direct: p = 0.021), but did not differ in behaviours (indirect: p = 0.184; direct: p = 0.497). CONCLUSIONS: Data suggest that female and limited/non-contact sport student-athletes intended to report more concussions, however differences did not translate to reporting behaviours.

Incorporating blood-based liquid biopsy information into cancer staging: time for a TNMB system?

Tissue biopsy is the standard diagnostic procedure for cancer. Biopsy may also provide material for genotyping, which can assist in the diagnosis and selection of targeted therapies but may fall short in cases of inadequate sampling, particularly from highly heterogeneous tumors. Traditional tissue biopsy suffers greater limitations in its prognostic capability over the course of disease, most obviously as an invasive procedure with potential complications, but also with respect to probable tumor clonal evolution and metastasis over time from initial biopsy evaluation. Recent work highlights circulating tumor DNA (ctDNA) present in the blood as a supplemental, or perhaps an alternative, source of DNA to identify the clinically relevant cancer mutational landscape. Indeed, this noninvasive approach may facilitate repeated monitoring of disease progression and treatment response, serving as a means to guide targeted therapies based on detected actionable mutations in patients with advanced or metastatic solid tumors. Notably, ctDNA is heralding a revolution in the range of genomic profiling and molecular mechanisms to be utilized in the battle against cancer. This review will discuss the biology of ctDNA, current methods of detection and potential applications of this information in tumor diagnosis, treatment, and disease prognosis. Conventional classification of tumors to describe cancer stage follow the TNM notation system, heavily weighting local tumor extent (T), lymph node invasion (N), and detectable metastasis (M). With recent advancements in genomics and bioinformatics, it is conceivable that routine analysis of ctDNA from liquid biopsy (B) may make cancer diagnosis, treatment, and prognosis more accurate for individual patients. We put forward the futuristic concept of TNMB tumor classification, opening a new horizon for precision medicine with the hope of creating better outcomes for cancer patients.

Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial.

OBJECTIVES: The present study constitutes the first randomized controlled trial to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function using functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency (i.e., reduce activation) and cognitive performance on a verbal learning task relative to placebo. METHODS: A total of 44 community-dwelling older adults (mean age=72 years) were randomly assigned to receive either placebo or L+Z supplementation (12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were created by subtracting active control trials from learning and recall trials. A flexible factorial model was employed to investigate the expected group (placebo vs. supplement) by time (baseline vs. post-intervention) interaction in pre-specified regions-of-interest. RESULTS: L and Z appeared to buffer cognitive decline on the verbal learning task (Cohen's d=.84). Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex (p < .05, family-wise-error corrected). However, these effects were in the direction of increased rather than decreased BOLD signal. Although the omnibus interaction was not significant during recall, within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only. CONCLUSIONS: L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. (JINS, 2018, 24, 77-90).