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Khellin is the key furanocoumarin of Ammi visnaga L. (Lam.) that exhibits various biological properties. This unique natural product has inspired the discovery of two first-in-class drugs, amiodarone and sodium cromoglycate. A wide range of analytical methods were generated while translating khellin scaffold into clinically used drugs; however, they have never been reviewed and critically assessed. The present review aims to review and evaluate the analytical techniques for the natural products, khellin, visnagin, and their inspired drugs, amiodarone and sodium cromoglycate. High-performance liquid chromatography (HPLC) is the extensively used technique in most analytical methods reported for these compounds; however, other techniques including the fluorimetry, luminescence spectrophotometry, potentiometry, voltammetry, FT-Raman spectroscopy, and ELISA were also employed. The review will be helpful for further basic and translational research on furanochromone and related scaffolds. [ABSTRACT FROM AUTHOR]

To determine the prevalence of non-use and limited use of cochlear implants. To find out the reasons for the same. This study was carried out among the paediatric patients who underwent cochlear implantation under the SHP* scheme in Civil Hospital, Ahmedabad between 2013 and 2020. Study Design: Retrospective cross-sectional study. Study Setting: Civil Hospital Ahmedabad. Sample Size: 150 paediatric patients. Patients were selected based on a random number generator. The data was collected through a telephonic interview based upon a preformed questionnaire. The study indicates that out of a total 150 participants, 109 (72.7%) used their cochlear implant regularly while 41 (27.3%) did not. Major issue faced by the participants was in the external device -damage to the device and monetary issues for its repair. The participants who have dropped the usage of their implants faced issues mostly after 2 years of usage. The age group of less than 3 years showed 15.6% of non-usage, while the age group of 3–6 years showed an increase to 34.5% of non-users. The age group of more than 6 years showed an even higher proportion (41.3%) of non-users. It is recommended that the government ensures the follow-up of the patients undergoing cochlear implantation for at least 2 years after the surgery. The proportion of non-users in the consecutive increasing age groups saw a rise in number. Therefore, it is recommended to divert the resources towards lower age groups to facilitate a better outcome. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM) has seen slow growth thus far in the maritime industry. Like other industries, maritime companies and institutions have started using AM for prototyping and product development needs but is now beginning to expand into production of end use parts and production tooling. The slow adoption can mainly be attributed to a previous lack of education in additive technology and strategies, current lack of reliability testing of additive machines in a marine environment, and the need for classification and certification of parts and machines before shipowners and crews will likely adopt for widespread use. This article provides a perspective of recent AMactivities within the industry and discusses the need for research in key areas before widespread utilization can occur. Current use includes a recent push in maritime education, surveys of maritime workers and stakeholders, and fabrication of replacement parts, propellers, and boat hulls. Prospective key areas with the need for further research include 1) use-cases for replacement parts on ship, 2) economic feasibility of putting 3D printers on board, 3) standards, certification, and quality assurance, and 4) reliability and repeatability in a marine environment. [ABSTRACT FROM AUTHOR]

Self‐emulsifying drug delivery system (SEDDS) is extensively used for enhancing the solubility, dissolution, and pharmacokinetics of poorly soluble drugs. Khellin is a natural product with multiple pharmacological activities and has inspired the discovery of two first‐in‐class drugs, amiodarone hydrochloride and sodium cromoglycate. The poor‐aqueous solubility is one of the limitations in developing this molecule. Herein, we aimed to improve the drug loading of khellin by developing its SEDDS formulation. A combination of castor oil, tetraethylene glycol, and Transcutol HP (10 : 30 : 60 v/v) was identified, inhibiting the drug's precipitation post‐dilution in an aqueous media. The optimized formulation, SB‐16KD, was characterized using 1H NMR, DSC, and FTIR to understand khellin's physical/chemical interaction with the formulation excipients. The in vitro dissolution studies of khellin in SB‐16KD correlated well with the oral pharmacokinetics in Wistar rats (1.6 vs. 1.7‐fold). The comparative oral pharmacokinetics of formulation against native khellin was performed at 45 mg/kg in Wistar rats. The results were promising, with 1.7‐fold higher plasma exposure by SEDDS formulation. Hence, the results warrant further developmental studies on SEDDS in dose reduction. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: The two most common procedures performed to treat obesity are Roux-En-Y gastric bypass (RNYGB) and laparoscopic sleeve gastrectomy (LSG). Due to changes in enteric absorption, bariatric surgery increases rates of nephrolithiasis. As population-based data are limited, we aimed to compare the incidence of kidney stones after RNYGB and LSG. Materials and Methods: We queried Explorys (Cleveland, OH), a database that aggregated data from 26 healthcare systems. We identified patients who were newly diagnosed with nephrolithiasis 3, 6, and 12 months after their RNYGB or LSG. Additionally, a multivariate analysis was conducted to investigate the association of nephrolithiasis with RNYGB as compared to LSG. This analysis adjusted for other risk factors, including age above 65, male gender, Caucasian race, diabetes mellitus, hypertension, primary hyperparathyroidism, gout, and obesity. Results: From 1999 to 2019, there were 11,480 patients who underwent RNYGB and 22,770 patients who underwent LSG. The incidence of nephrolithiasis in the RNYGB cohort at all three time points was higher than in the LSG cohort (3 months, 7.1% vs. 2.4%; 6 months, 6.6% vs. 2.0%; 1 year, 5.8% vs. 1.4%; P < 0.001). After the multivariate analysis, it was found that, though both RNYGB and LSG were independently associated with the development of nephrolithiasis, the risk of nephrolithiasis was higher in those who underwent RNYGB compared to those who underwent LSG (OR 1.594, 95% CI 1.494 to 1.701, P < 0.001). Conclusion: RNYGB is associated with a higher risk of nephrolithiasis when compared to LSG. [ABSTRACT FROM AUTHOR]

Background: The development of guidelines by gastroenterology societies increasingly stresses evidence-based endoscopic practice. Aims: We performed a systematic assessment to determine whether endoscopic video teaching platforms incorporate evidence-based educational strategies and methods in order to disseminate guideline-based endoscopic management strategies. Methods: Platforms with a video component were systematically identified using the Google search engine, Apple and Android application stores, and searching four major gastroenterology society websites and three known platforms, to identify all relevant platforms. Two video samples from each teaching platform were reviewed independently by two authors and assessed for use of a priori defined principles of evidence-based medicine, as determined by consensus agreement and for the use of simulation. Results: Fourteen platforms were included in the final analysis, and two videos from each were analyzed. One of the 14 platforms used simulation and incorporated evidence-based medicine principles consistently. Nine of the 14 platforms were not transparent in regard to citation. None of the platforms consistently cited the certainty of evidence or explained how evidence was selected. Conclusions: Education of guideline-based endoscopic management strategies using principles of evidence-based medicine is under-utilized in endoscopic videos. In addition, the use of cognitive simulation is absent in this arena. There is a paucity of evidence-based cognitive endoscopy simulators designed for fellows that incorporate systematic evaluation, and efforts should be made to create this platform. [ABSTRACT FROM AUTHOR]

According to the Environmental Protection Agency, transportation is the largest contributor of greenhouse gas emissions (28% of total emissions). Electric vehicles have remarkably grown in popularity and represent a greener future for the automotive industry. This growth has prompted lubricant and grease technology to adapt to an entirely new environment, which is exposed to new factors including external electric currents/fields and extreme temperatures and pressures originating from electric motors and power electronics. Consequently, novel lubricants and greases need to be developed and explored to ultimately improve fuel efficiency and performance. Nano‐additives have offered exceptional opportunities to enhance electrical, thermal and tribological properties of the lubricants and greases used. It is thus vital to fully explore and understand the effects of nanoparticles' addition to lubricants and greases, as well as the mechanisms by which improvements are obtained. This perspective summarises the recent trends of developing lubricants and greases for electric vehicles. [ABSTRACT FROM AUTHOR]

Background: There is no practical dementia risk score in the clinical setting. Objective: To derive and validate a score obtained by a rapid and simple assessment, which guides primary care providers in predicting the risk of dementia among older adults. Design: A total of 4178 participants from three longitudinal cohorts (mean age at baseline = 76.8 [SD = 7.6] years), without baseline dementia, followed annually for a median of 10 years (IQR: 5 to16 years, Reverse Kaplan-Meier). Participants: To derive the score, we used data from 1,780 participants from the Rush Memory and Aging Project (93% White). To validate the score, we used data from 1,299 participants from the Religious Order Study (92% White), and to assess generalizability, 679 participants from the Minority Aging Research Study (100% Black). Measurements: Clinician-based dementia diagnosis at any time after baseline and predictive variables associated with dementia risk that can be collected in a primary care setting: demographics, clinical indicators, medical history, memory complaints, cognitive and motor tests, and questions to assess functional disability, depressive symptoms, sleep, social isolation, and genetics (APOE e4 and AD polygenic risk score). Results: At baseline, age, memory complaint, the ability to handle finances, the recall of the month, recall of the room, and recall of three words, were associated with the cumulative incidence of dementia, in the derivation cohort. The discrimination of the RADaR (Rapid Risk Assessment of Dementia) was good for the derivation and external-validation cohorts (AUC3 years = 0.82–0.86), compared to the overall discrimination of age alone (AUC3 years = 0.73), a major risk factor for dementia. Adding genetic data did not increase discrimination. Limitations: Participants were volunteers, may not represent the general population. Conclusions: The RADaR, derived from community-dwelling older persons, is a brief and valid tool to predict dementia risk at 3 years in older White and Black persons. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to present a comprehensive perspective on how tribology and sustainability are related and intertwined and are linked to CO2 emissions. This paper emphasizes on how tribological aspects affect everybody's life and how tribological research and progress can improve energy efficiency, sustainability and quality of life. Design/methodology/approach: Based upon available data and predictions for the next 50 years, the potential of tribological research and development is addressed. Findings: The effects of tribological design can significantly increase energy savings and reduce CO2 emissions. Taking advantage of tribological technologies and applying them to current infrastructure would have the largest energy savings coming from the transportation and power generation at 25% and 20%, respectively. Implementing these technologies can also cut down global CO2 emissions by about 1,460 megatons of CO2 per year in the immediate future and 3,140 megatons of CO2 per year in the long term. The extraction and processing of resources inevitably generates CO2. Doubling the lifetime of machine components and the use of circular economy reduces the material footprint with associated reductions in CO2. Originality/value: This perspective summarizes concisely the interrelation of tribology and sustainability with CO2. Peer review: The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-09-2020-0356/ [ABSTRACT FROM AUTHOR]

Nanostructured iron–zirconium oxides (NIZOs), with Fe-to-Zr molar ratio of 1:1 and 1:2, have been found to show high adsorption efficiency toward Pb2+ from aqueous solution. The NIZO was synthesized by the co-precipitation method and characterized in terms of XRD, TEM, SEM–EDX, BET surface area analysis, TGA, FT-IR spectroscopy and zeta potential measurement. The data of adsorption of Pb2+ on the NIZO, under optimized condition of pH, Pb2+ concentration, adsorbent amount, time and temperature, were fitted in Langmuir, Freundlich and Temkin adsorption model, and the data showed the best agreement with Langmuir model with R2 = 0.990 and 0.994 for Fe/Zr molar ratio = 1:1 and 1:2, respectively. The thermodynamic studies showed that the adsorption of Pb2+ on the NIZO proceeds spontaneously and exothermically through the involvement of weak van der Waals forces. Further, the adsorption of Pb2+ on the NIZO was found to follow pseudo-second-order kinetics. [ABSTRACT FROM AUTHOR]

Brain donation in studies on aging remains a critical pathway to discovering and improving preventive measures and treatments for Alzheimer's dementia and related disorders. Brain donation for research is almost exclusively obtained from non-Latinx Whites of higher socioeconomic status in the United States. Despite persistent efforts, it has been difficult to obtain consent for brain donation among diverse participants. Hence, our understanding of Alzheimer's dementia and related disorders remains incomplete. The purpose of this methodological paper was to propose and outline a two-phase sequential mixed-methods research study design to identify barriers and facilitators of brain donation among diverse older adults. The first phase will consist of qualitative focus groups using a three (participant minority status: African American, Latinx, or White of lower income) by two (participant brain donation decision: consented or declined) design. The second phase will include statistical analyses of quantitative measures of existing data representing categories of variables that may be associated with decision making regarding brain donation. Next steps must include conducting qualitative focus groups and subsequent data analyses, resulting in overarching themes. Afterward, qualitative themes will be operationalized using quantitative variables for statistical analyses. This proposed study design can provide the foundation for developing and implementing effective and culturally competent survey instruments, educational tools, and intervention strategies in an effort to facilitate brain donation among diverse older adults [ABSTRACT FROM AUTHOR]

Importance: Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million.Observations: Dementia is an acquired loss of cognition in multiple cognitive domains sufficiently severe to affect social or occupational function. In the United States, Alzheimer disease, one cause of dementia, affects 5.8 million people. Dementia is commonly associated with more than 1 neuropathology, usually Alzheimer disease with cerebrovascular pathology. Diagnosing dementia requires a history evaluating for cognitive decline and impairment in daily activities, with corroboration from a close friend or family member, in addition to a thorough mental status examination by a clinician to delineate impairments in memory, language, attention, visuospatial cognition such as spatial orientation, executive function, and mood. Brief cognitive impairment screening questionnaires can assist in initiating and organizing the cognitive assessment. However, if the assessment is inconclusive (eg, symptoms present, but normal examination findings), neuropsychological testing can help determine whether dementia is present. Physical examination may help identify the etiology of dementia. For example, focal neurologic abnormalities suggest stroke. Brain neuroimaging may demonstrate structural changes including, but not limited to, focal atrophy, infarcts, and tumor, that may not be identified on physical examination. Additional evaluation with cerebrospinal fluid assays or genetic testing may be considered in atypical dementia cases, such as age of onset younger than 65 years, rapid symptom onset, and/or impairment in multiple cognitive domains but not episodic memory. For treatment, patients may benefit from nonpharmacologic approaches, including cognitively engaging activities such as reading, physical exercise such as walking, and socialization such as family gatherings. Pharmacologic approaches can provide modest symptomatic relief. For Alzheimer disease, this includes an acetylcholinesterase inhibitor such as donepezil for mild to severe dementia, and memantine (used alone or as an add-on therapy) for moderate to severe dementia. Rivastigmine can be used to treat symptomatic Parkinson disease dementia.Conclusions and Relevance: Alzheimer disease currently affects 5.8 million persons in the United States and is a common cause of dementia, which is usually accompanied by other neuropathology, often cerebrovascular disease such as brain infarcts. Causes of dementia can be diagnosed by medical history, cognitive and physical examination, laboratory testing, and brain imaging. Management should include both nonpharmacologic and pharmacologic approaches, although efficacy of available treatments remains limited. [ABSTRACT FROM AUTHOR]

Pure, 3 mol% and 5 mol% Sr-doped cerium oxide nanoparticles were synthesized by facile aqueous co-precipitation method using cerium nitrate hexahydrate and strontium chloride hexahydrate as the precursors without using any capping agent. The synthesized material was characterized by XRD, SEM, EDX, TEM, Raman spectroscopy and UV–Vis spectroscopic techniques. SEM analysis showed agglomeration of the particles. The Debye–Scherrer analysis revealed fluorite structure of the synthesized material with crystallite size in 6–10 nm range. TEM confirmed the spherical morphology of the particles and particle size distribution in the range of 5–8 nm. UV–Vis spectroscopic study revealed that Sr-doping led to increase in the band gap from 3.2 to 3.7 eV and shifting of absorption edge to the lower wavelength. The blue shift in the band gap with the dopant concentration shows that the band gap of doped cerium oxide nanoparticles can be tuned with variation in the dopant concentration. [ABSTRACT FROM AUTHOR]

Currently, there are enormous Risk Factors (RFs) threating the safety of Oil and Gas Pipelines (OGPs) at all stages of projects. However, there is a lack of information about the root causes of pipeline failures and an absence of trusted data about the "probability and severity" levels of the RFs; this hinders the risk management in such projects. To improve the safety level of OGPs, this paper aims to explore stakeholders' perceptions about pipeline failures issues to analyze the RFs and recommend effective Risk Mitigation Methods (RMMs). Due to the lack of trusted data about the RFs and RMMs, this paper started with extensive investigations to identify the critical RFs and the applied RMMs in OGP projects in different circumstances. The findings of these investigations were used to design a questionnaire survey, which was distributed to analyze the "probability and severity" levels of the RFs and evaluate the "usability and effectiveness" degrees of the suggested RMMs. The survey results revealed that RFs related to Third-Party Disruption (TPD) including sabotage and terrorism, corruption and insecure areas are the most severe RFs. Additionally, based on the survey some RMMs such as anti-corrosion efforts, laying the pipelines underground and using technologically advanced risk-monitoring systems were found to be effective RMMs. These results were found to be varied based on the stakeholders' occupation in the projects; for example, the overall survey results indicated that terrorism and sabotage is the most critical RF, while the planners and the researchers identified corruption as the most critical one. It was also observed that using anti-corrosion measures such as isolation and cathodic protection would be the most effective RMM, while the other stakeholders have different perceptions like moving the pipelines underground an advanced risk-monitoring system are the most effective RMMs as indicated by the consultant, planner or designer and researches respectively. [ABSTRACT FROM AUTHOR]

We report the imaging characteristics of focal choroidal excavation (FCE) and associated choroidal neovascular membrane (CNVM) and interpret the probable etiopathogenesis of FCE through findings in four patients detected by spectral-domain optical coherence tomography (SD-OCT). FCE was found as an acquired entity in two of our cases subsequent to treatment of CNVM, whereas in the two other cases FCE was pre-existing. Furthermore, association of FCE with pachychoroid spectrum is reaffirmed through this case series. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend empirical vancomycin or linezolid for patients with suspected pneumonia at risk for methicillin-resistant Staphylococcus aureus (MRSA). Unneeded vancomycin or linezolid use may unnecessarily alter host flora and expose patients to toxicity. We therefore sought to determine if rapid testing for MRSA in BAL can safely decrease use of vancomycin or linezolid for suspected MRSA pneumonia.Methods: Operating characteristics of the assay were initially validated against culture on residual BAL. A prospective, unblinded, randomized clinical trial to assess the effect of antibiotic management made on the basis of rapid diagnostic testing (RDT) compared with usual care was subsequently conducted, with primary outcome of duration of vancomycin or linezolid administration. Secondary end points focused on safety.Results: Sensitivity of RPCR was 95.7%, with a negative likelihood ratio of 0.04 for MRSA. The clinical trial randomized 45 patients: 22 to antibiotic management made on the basis of RDT and 23 to usual care. Duration of vancomycin or linezolid administration was significantly reduced in the intervention group (32 h [interquartile range, 22-48] vs 72 h [interquartile range, 50-113], P < .001). Proportions with complications and length of stay trended lower in the intervention group. Hospital mortality was 13.6% in the intervention group and 39.1% for usual care (95% CI of difference, -3.3 to 50.3, P = .06). Standardized mortality ratio was 0.48 for the intervention group and 1.18 for usual care.Conclusions: A highly sensitive BAL RDT for MRSA significantly reduced use of vancomycin and linezolid in ventilated patients with suspected pneumonia. Management made on the basis of RDT had no adverse effects, with a trend to lower hospital mortality.Trial Registry: ClinicalTrials.gov; No. NCT02660554; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis and Alzheimer's disease are common diseases of aging that would seem to be unrelated, but may be linked through the influence of bone-derived signals on brain function. The aim of the current study is to investigate the relationship between circulating levels of bone-related biomarkers and cognition.Methods: The population included 103 community-dwelling older individuals with memory concerns but without cognitive impairment. A global cognition summary measure was collected at baseline and 6, 12, and 18 months post-enrollment by converting raw scores from 19 cognitive function tests to z-scores and averaging. Baseline plasma concentrations of bone-related biomarkers, including undercarboxylated, carboxylated, and total osteocalcin, parathyroid hormone, C-terminal telopeptide of collagen 1 (CTX-1), procollagen type 1 amino-terminal propeptide, osteoprotegrin, osteopontin, Dickkopf WNT signaling pathway inhibitor 1 (Dkk1), sclerostin, and amyloid β peptides (Aβ40 and Aβ42), were measured.Results: Using sex, age, and education-adjusted mixed-effects models, we found that baseline levels of TNF-related apoptosis-inducing ligand (TRAIL; p < .001), Dkk1 (p = .014), and CTX-1 (p = .046) were related to the annual rate of change of global cognition over the 18 month follow-up. In cognitive domain-specific analysis, baseline TRAIL was found to be positively related to the annual rate of change in episodic (p < .001) and working memory (p = .016), and baseline Dkk1 was positively related to semantic memory (p = .027) and negatively related to working memory (p = .016).Conclusions: These results further confirm the link between bone and brain health and suggest that circulating levels of bone-related biomarkers may have diagnostic potential to predict worsening cognition. [ABSTRACT FROM AUTHOR]

We examined the association between racial/ethnic minority segregation and low birth weight (LBW) in Chicago and Toronto communities. While previous work has documented the importance of contextual effects on LBW, these studies have usually been conducted within a single city. We used Pearson correlation coefficients and OLS regression models to examine potential variability in the association between racial/ethnic minority segregation and LBW in Chicago (N = 77 communities) and Toronto (N = 140 communities). Results indicate that racial/ethnic minority segregation, unemployment, and low educational attainment are not associated with LBW in Toronto, while these indicators have strong and significant associations with LBW in Chicago. In a combined model with data from both cities, a 10% increase in minority composition is associated with a 0.5% increase in LBW, controlling for the effects of unemployment and low educational attainment. Stratified models show that this effect is only significant in Chicago, and subsequent models revealed opposite effects for percentage non-Hispanic Black and percentage Hispanic. Future research should consider additional cities for comparative analysis. Such work could test the notion that Chicago and Toronto represent opposite sides of a spectrum, reflecting variability in how social determinants map on to public health outcomes. Future research should also examine the significant heterogeneity observed in highly segregated communities, particularly in Chicago. [ABSTRACT FROM PUBLISHER]

Background and study aim Our aim was to evaluate the first use in humans of a new, single-use, digital, single-operator intraductal cholangiopancreatoscopy system (IDCP). Patients and methods Data were collected retrospectively from four US institutions between February 2015 and April 2015. The visual impression of neoplasia or benign findings with IDCP was determined by the performing endoscopist. High grade dysplasia, intraductal papillary mucinous neoplasm, neuroendocrine tumor, and malignancy were categorized as neoplasia. Benign disease was defined as the absence of neoplasia during ≥ 6 months of follow-up. Results Patients (n = 108) with indeterminate strictures, dilatation, or difficult stones underwent IDCP. Of 74 patients with indeterminate stricture or dilatation, 29 (39 %) had neoplasia, of which 25 were confirmed by miniature biopsy forceps, 2 by surgical pathology, and 2 by the presence of metastatic disease on follow-up imaging. In patients with benign disease, 15 had concentric stenosis or normal/erythematous changes, 5 had low papillary mucosal projections, 6 had coarse granular mucosa, and 4 had nodular mucosa. Findings in patients with neoplastic disease included dilated, tortuous vessels ("tumor vessels"; n = 13), irregular margins with partial occlusion of the lumen (infiltrative stricture, n = 12), villous or nodular mass (n = 9), and finger-like villiform projections (n = 5). Operating characteristics for indeterminate stricture or dilatation were: 97 % sensitivity, 93 % specificity, 90 % positive predictive value, 98 % negative predictive value. Targeted biopsy yielded 86 % sensitivity and 100 % specificity. Stone clearance was noted in all cases. Adverse events occurred in 3 %. Conclusion The new IDCP system provides enhanced image resolution, and may improve the ability to target difficult stones and diagnose indeterminate strictures. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia and the prevalence will increase dramatically in the next decades. Although exercise has shown benefits for people with dementia due to AD as well as their caregivers, the impact of a dyadic exercise intervention including both groups as study participants remains to be determined. The authors review the current clinical evidence for dyadic exercise interventions, which are exercise regimens applied to both the person with dementia and the caregiver. A total of 4 controlled trials were reviewed. This review shows that dyadic exercise interventions are feasible and may produce a positive effect on functional independence and caregiver burden. However, there was insufficient evidence to support a benefit of dyadic exercise intervention on cognitive performance and on behavioral and neuropsychiatric symptoms in participants with dementia due to AD. A dyadic exercise intervention improves functional independence and caregiver burden. However, there is a need for well-designed randomized controlled clinical trials to confirm these benefits and to investigate several important points such as the effects of a dyadic exercise intervention on cognitive and noncognitive outcomes of AD, the optimal intensity of exercise training, and the cost effectiveness of such a program. [ABSTRACT FROM AUTHOR]

Past models and tools that support in the decision making process based on Asset Management Principles (AMP) are lacking in terms of the effective outcomes and transparency of the process in the highway maintenance. There is also little research on how to align the decision areas when applying AMP and how to improve the inclusive effectiveness. Hence, the paper focuses on examining the challenges and prospects of applying AMP in a highway maintenance agency or department. An exploratory research method was used through an extensive review of literature and an industry survey. The findings from the literature and case study review were used to design a questionnaire and conduct the survey. The survey results revealed that the AMP are only being implemented ineffectively in maintaining highways, and a strong commitment is required to improve the asset management capability for effective use of the asset data. It is highly recommended that the Highway Agency should issue a guideline for implementing asset management policy and also encourage associate departments to achieve asset management maturity level 3 so that ISO55000 certification can be achieved. The study concludes that there is still substantial work needed within the asset management process, particularly in highway maintenance before its effectiveness can be realised and measured. [ABSTRACT FROM AUTHOR]

Objectives To investigate whether the use of antihypertensive and statin medication in very old adults is associated with the level of motor performance. Design Cross-sectional study. Settings A community-based study recruited from over 40 residential facilities across the metropolitan Chicago area. Participants Community-dwelling very old adults (n = 1520; mean age 80.2; standard deviation 7.7). Measurements Eleven motor performances were summarized using a composite motor score. All prescription and over the counter medications taken by participants were inspected and coded using the Medi-Span Data Base System. Demographic characteristics and medical history were obtained by means of detailed interview and medical examinations. Results In multiple linear regression models, antihypertensive medications were associated with global motor score [β = −0.075, standard error (SE) 0.011, P < .001]. Thus, motor function in an individual with antihypertensive medication, was on average, about 7.5% lower than an age-, sex-, and education-matched individual without antihypertensive medication. The number of antihypertensive medications, which were being used had an additive effect, such that a reduction in the level of motor function was observed with each additional medication, and receiving 3 or more antihypertensive medications was associated with about a 15% reduction in the level of motor function. The association between antihypertensive medications and motor function was robust, and remained unchanged after adjusting for confounding by indication using several potentially confounding variables: smoking, hypertension, diabetes, stroke, congestive heart failure, myocardial infarction, and intermittent claudication (β = −0.05, SE 0.015, P = .001). In contrast, the use of statin medications was not related to motor function (unadjusted: β = 0.003, SE 0.015, P = .826; fully adjusted: β = 0.018, SE 0.014, P = .216). Conclusions The use of antihypertensive medications is associated with a lower level of motor function in very old adults. The nature of this association warrants further investigation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. In humans, AD becomes symptomatic only after brain changes occur over years or decades. Three contiguous phases of AD have been proposed: (i) the AD pathophysiologic process, (ii) mild cognitive impairment due to AD, and (iii) AD dementia. Intensive research continues around the world on unique diagnostic markers and interventions associated with each phase of AD. In this review, we summarize the available evidence and new therapeutic approaches that target both amyloid and tau pathology in AD and discuss the biomarkers and pharmaceutical interventions available and in development for each AD phase. [ABSTRACT FROM AUTHOR]

The article discusses a study focused on how surrogate characteristics impact clinical decision making for critically ill patients. Topics discussed include patient-surrogate decision maker relationship, surrogate's understanding of condition of the patient, and physicians' strategies to discuss end-of-life decision making for critically ill patients with surrogate decision makers.

• Mole fraction solubility of khellin in eight mono-solvents at 298.15–323.15 K. • Thermodynamic equilibrium solubility correlated using non-linear multivariate analysis. • DSC analysis to understand polymorphic changes in the presence of solvents. • Molecular electrostatic potential analysis and its correlation to the solubility. • The data presented here is crucial for the process chemistry. Khellin is a medicinally important furanocoumarin class of natural product. It has led to the discovery of two first-in-class drugs, which embarks the potential of the scaffold for future research. The solubility estimation is one of the vital parameters during the preclinical development of the molecule. Thus, an objective of the present study was to determine the mole fraction solubility of khellin in eight mono-solvents at the temperature range of 298.15–323.15 K. The thermodynamic equilibrium solubility of khellin, correlated using non-linear multivariate analysis. The maximum mole fraction solubility of khellin at 323.15 K was observed as 1.525 × 10−2 in DMSO followed by 1-butanol (5.291 × 10−3), PEG 400 (5.111 × 10−3), ethanol (3.384 × 10−3), methanol (3.318 × 10−3), 2-propanol (2.533 × 10−3), PEG 200 (2.306 × 10−3) and water (9.02 × 10−5). We also studied the correlation of molecular electrostatic potential of khellin with its solubility. This data will be crucial for the drug discovery and development teams working on the medicinal chemistry of the khellin scaffold. [ABSTRACT FROM AUTHOR]

The article discusses the representations of the age of mechanical reproduction in the novels "Dracula" by Bram Stoker and "Le Chateau des Carpathes." Topics covered include how "Le Chateau des Carpathes" evokes the uncanny aspects of modernity in its portrayal of the Baron Rodolphe de Gortz's compulsive listening to a personal phonograph recording and the triumph of the simulacrum in both "Dracula" and "Le Chateau."

A literary criticism for books including "Der Process" by Franz Kafka and "1984" by George Orwell are presented. It outlines the data-collection and surveillance practices of contemporary Western societies. It also discusses the architectural paradigm of a disciplinary modernity and internalization of social norms traced by German sociologist Norbert Elias.

Our laboratory previously described the oncogenic properties of metabotropic glutamate receptor 1 (mGluR1) in melanocytes. mGluR1 transformed immortalized mouse melanocytes in vitro and induced vigorous tumor formation in vivo. Subsequently, we observed the activation of PI3K/AKT in mGluR1-mediated melanocytic tumorigenesis in vivo. In particular, we identified AKT2 being the predominant isoform contributing to the activation of AKT. Suppression of Grm1 or AKT2 using an inducible Tet-R siRNA system resulted in a 60 or 30% reduction, respectively, in in vivo tumorigenesis. We show that simultaneous downregulation of Grm1 plus AKT2 results in a reduction of approximately 80% in tumor volumes, suggesting that both mGluR1 and AKT2 contribute to the tumorigenic phenotype in vivo. The discrepancy between the mild in vitro transformation characteristics and the aggressive in vivo tumorigenic phenotypes of these stable mGluR1-melanocytic clones led us to investigate the possible involvement of other growth factors. Here, we highlight a potential crosstalk network between mGluR1 and tyrosine kinase, insulin-like growth factor 1 receptor (IGF-1R). [ABSTRACT FROM AUTHOR]

Abstract: Accurate information of working locations is vital for efficient resource planning, safety of the construction site and monitoring the weekly progress of earthworks, which is missing in the existing linear scheduling methods. Construction managers have to depend on the subjective decisions for resources allocation and progress monitoring from location aspects. This has caused uncertainties in planning and scheduling, and consequently delays and cost overruns of projects. In this context, a prototype computer-based model was developed using the theory of the location-based planning. An arithmetic algorithm was designed by incorporating road design data, sectional quantities, variable productivity rates and haulage distance. This paper focuses on the improvement and demonstration of the model functions through a case study experiment, which include the automatic generation of location-based earthwork schedules and the optimisation of the weekly resource allocation when and where necessary from the location aspects, considering different options such as construction sequences of the cut/fill sections, site access points and the equipment sets with known productivity rates. The study concluded that the model is a decision supporting tool that assists in the resources planning, identifying time–space congestion, monitoring the activities progress on a weekly basis from the location aspects, and reducing the gap when communicating the scheduling information amongst the construction site teams. [Copyright &y& Elsevier]

Gaston Leroux's 1910 novel Le Fantôme de l'Opéra is the origin of a world-famous modern myth that has perdured for over a century. Only recently, however, has it begun to receive serious critical attention, which thus far has overlooked one crucial source: the surviving manuscript of one of Leroux's earlier drafts, which differs considerably from the published text. This article reveals, for the first time, how the manuscript explicitly cites a hitherto unexamined inspiration for the novel, from which Leroux derived his central plot device of the eponymous Phantom's skeleton. This fictional cadaver has its roots in an apparently historical anecdote concerning the use of a real skeleton in performances of the Paris Opéra's 1841 production of Le Freischütz. Examining the veracity of this theatrical legend, however, this article concludes that it is apocryphal. As a fictionalization of an already falsified account, therefore, Le Fantôme is a paradigmatic example of the European Gothic. [ABSTRACT FROM PUBLISHER]

Introduction Souvenaid® containing Fortasyn® Connect is a medical food designed to support synapse synthesis in persons with Alzheimer's disease (AD). Fortasyn Connect includes precursors (uridine monophosphate; choline; phospholipids; eicosopentaenoic acid; docosahexaenoic acid) and cofactors (vitamins E, C, B12, and B6; folic acid; selenium) for the formation of neuronal membranes. Whether Souvenaid slows cognitive decline in treated persons with mild-to-moderate AD has not been addressed. Methods In a 24-week, double-masked clinical trial at 48 clinical centers, 527 participants taking AD medications [52% women, mean age 76.7 years (Standard Deviation, SD = 8.2), and mean Mini-Mental State Examination score 19.5 (SD = 3.1, range 14-24)] were randomized 1:1 to daily, 125-mL (125 kcal), oral intake of the active product (Souvenaid) or an iso-caloric control. The primary outcome of cognition was assessed by the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Compliance was calculated from daily diary recordings of product intake. Statistical analyses were performed using mixed models for repeated measures. Results Cognitive performance as assessed by ADAS-cog showed decline over time in both control and active study groups, with no significant difference between study groups (difference =0.37 points, Standard Error, SE = 0.57, p = 0.513). No group differences in adverse event rates were found and no clinically relevant differences in blood safety parameters were noted. Overall compliance was high (94.1% [active] and 94.5% [control]), which was confirmed by significant changes in blood (nutritional) biomarkers. Conclusions Add-on intake of Souvenaid during 24 weeks did not slow cognitive decline in persons treated for mild-to-moderate AD. Souvenaid was well tolerated in combination with standard care AD medications. [ABSTRACT FROM AUTHOR]

Article III of the U.S. Constitution requires standing to sue for federal subject matter jurisdiction over a case. Under the modern test for standing, plaintiffs must show that they suffered some concrete and imminent injury-in-fact as a result of the illegal conduct of the defendant. While many scholars and judges have critiqued the U.S. Supreme Court's development and application of the injury-in-fact requirement, relatively little attention has been paid to disturbing racial double standards in the Court's standing jurisprudence. When racial minorities have brought equal protection challenges against programmatic governmental discrimination, the Court has applied standing doctrine strictly. But when white plaintiffs have brought equal protection challenges against racial remediation programs, the Court has continually relaxed standing requirements. This Comment seeks to illustrate and analyze this racial divide by comparing Supreme Court cases raising the issue of standing in the equal protection context. Applying a Critical Race Theory perspective, this Comment ultimately concludes that this racial contradiction in standing doctrine stems from the Court's modern doctrinal push to uproot de jure racial discrimination and to leave de facto racial discrimination alone. Consequently, this Comment suggests either correcting the resulting double standard in standing requirements or eliminating the injury-in-fact requirement altogether. [ABSTRACT FROM AUTHOR]

[Display omitted] • Critical assessment of synovial joint lubrication mechanisms. • Elucidation of the role of individual constituents and proteins for lubrication. • Discussion of beneficial material combinations for prosthesis and joint's longevity. • Evaluation of the effects of physical variables in prosthetic lubrication. • Summary of existing research challenges and future research directions. Synovial fluids are complex fluids responsible for the exceptional lubrication present in synovial joints. These fluids consist of various constituents, including hyaluronic acid, surface-active proteins (i.e., lubricin), surface-active phospholipids, as well as various other proteins such as human serum albumin and γ -globulin seric proteins, each of them playing an essential role in lubrication. Being the key to the most efficient biotribological systems, this article is intended to review the current understanding of the underlying lubrication mechanisms of the synovial fluids enables prospective usage in numerous applications, especially as a lubricant for hip and knee prosthetics in combatting osteoarthritis. Current research focuses on the determination of the role of proteins in prosthetic lubrication, optimal material combinations for prosthesis, and the effects of relevant physical variables in prosthetic lubrication. The characterization of prosthetic lubrication and wear mechanisms by synovial fluids represents a prominent challenge in tribological research, yet also an important hurdle to overcome towards optimal lubrication of articular prosthetics. [ABSTRACT FROM AUTHOR]

Background: This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. Methods: Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. Results: Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was −0.062 (SE = 0.005), −0.081(SE = 0.011), and −0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = −0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). Conclusions: Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications. [ABSTRACT FROM AUTHOR]

Lower hemoglobin levels have been associated with cognitive decline in older persons. The objective of this study was to investigate the relationship between lower hemoglobin levels and common, age-related neuropathologies associated with cognitive decline. Hemoglobin and neuropathology measures were available in 113 deceased, community-dwelling, older adults participating in the Rush Memory and Aging Project, a prospective, observational, clinical pathology study of aging. The mean hemoglobin level was 13.0 g/dL (SD = 1.4) and was measured 3.2 (SD = 1.3) years prior to death. Thirty-five participants had at least one chronic macroscopic infarction and twenty-nine had at least one chronic microscopic infarction. Eleven participants had Lewy Bodies. The mean Alzheimer's disease pathology score based on a summary measure of neuritic plaques, diffuse plaques, and neurofibrillary tangles was 0.56 unit (SD = 0.56; range = 0, 2.34). Using logistic regression models adjusted for age at death, gender, and education, each g/dL lower hemoglobin level increased the odds for having a chronic macroscopic infarction by 37% (95% CI = 1.01, 1.86) but not for having a chronic microscopic infarction (OR = 1.11; 95% CI = 0.82, 1.52) or Lewy Bodies (OR = 1.07; 95% CI = 0.68, 1.68). In an adjusted multiple regression model, hemoglobin level was not associated with the global AD pathology measure (parameter estimate = -0.02, SE = 0.03, p = 0.6). In secondary analyses, lower hemoglobin levels were associated with higher odds of having a chronic macroscopic infarction in a subcortical region but not with higher total subcortical chronic macroscopic infarction volume. In conclusion, lower hemoglobin levels appear to be associated with chronic macroscopic infarctions but not other common age-related neuropathologies. [ABSTRACT FROM AUTHOR]

Background. Maintaining spatial movement through the environment is an important feature of healthy aging. We examined whether being licensed to drive is associated with maintaining spatial movement in older persons initially reporting maximum spatial mobility. Methods. From the Rush Memory and Aging Project, 571 nondemented, community-dwelling older persons were identified with (i) baseline data on driving status, (ii) baseline report of spatial mobility to the largest life space zone, and (iii) at least one annual follow-up evaluation. Incident constriction of life space was the primary outcome of interest. Results. Over an average follow-up of 4.3 years, 303 participants reported incident constriction of life space. In a proportional hazards model adjusted for age, sex, and education, having a valid driver's license at baseline was associated with a decreased hazard of reporting a life space constriction (hazard ratio = 0.39; 95% confidence interval = 0.29–0.54). Results were unchanged after controlling for number of vascular risk factors and vascular diseases, low visual acuity, social isolation, and gait speed. Of participants reporting incident life space constriction, 188 subsequently reported reexpansion of spatial mobility to the largest zone of life space. Having a valid driver's license was associated with a greater likelihood of life space recovery (hazard ratio = 2.00; 95% confidence interval = 1.27–3.17). Conclusion. In older persons, having a valid driving license was associated with reduced hazard of reporting life space constriction and a greater likelihood of life space recovery if incident life space constriction occurred. [ABSTRACT FROM PUBLISHER]

Alzheimer's disease (AD) is a neurodegenerative condition associated with cognitive loss, behavioural changes, functional ability decline and caregiver burden. Given the worldwide public health impact of AD, novel interventions to reduce suffering experienced by AD patients need to be developed. Foods may offer a mechanism for intervention complementary to drugs, devices, biologicals and vaccines. Apart from foods with health claims (including dietary supplements), medical foods are also being explored as an intervention option. The purpose of this article is to describe how medical foods may complement other interventions for AD patients by: (i) defining what a medical food is; (ii) discussing whether AD is a condition amenable to medical food intervention; (iii) reviewing current clinical trial data on medical foods used in participants with AD; and (iv) highlighting steps needed to establish a more comprehensive framework for developing medical foods for AD. While medical foods may be defined differently in other countries, the US Orphan Drug Act of 1998 defined a medical food as a food formulated for enteral intake, taken under physician supervision, and intended to meet the distinctive nutritional requirements identified for a disease or condition. For AD to be amenable to medical food intervention, it must: (i) result in limited or impaired capacity to ingest, digest, absorb or metabolize ordinary food- stuff or certain nutrients; or (ii) have unique, medically determined nutrient requirements; and (iii) require dietary management that cannot be achieved by modification of the normal diet alone. While these criteria are most likely met in advanced AD, identifying unique nutritional requirements in early AD that cannot be met by normal diet modification requires a better under- standing of AD pathophysiology. A PubMed search using the terms 'medical food' and 'Alzheimer', limited to clinical trials published in English with human participants with AD aged >65 years and supplemented by other articles known to meet the inclusion criteria, revealed that only two medical foods, AC-1202 and Souvenaid® with Fortasyn Connect™, have clinical trial results available for discussion. As medical food development for AD is a relatively new endeavour, a window of opportunity exists for all stakeholders to develop a comprehensive framework for assuring that medical food interventions for AD achieve the highest possible scientific and ethical standards to warrant commercialization. [ABSTRACT FROM AUTHOR]

Abstract: Background: Excessive daytime sleepiness (EDS) and nocturnal sleep disruption are common in Alzheimer’s disease (AD). However, little is known regarding risk factors for developing EDS and sleep disruption in AD. In AD, EDS is associated with parkinsonian motor features (PF), which are associated with faster cognitive decline. The primary aim of this exploratory study was to evaluate whether differences in EDS and nocturnal sleep disruption exist between AD participants with versus without PF. Methods: Thirty-six participants with mild AD were evaluated for PF using the modified motor UPDRS (mmUPDRS) scoring system and classified according to absence (AD−PF, n =19) or presence (AD+PF, n =17) of PF. EDS was assessed using questionnaires and a multiple sleep latency test (MSLT) performed the day after nocturnal polysomnogram. Participants were considered “Sleepy” or “Not Sleepy” according to mean MSLT scores (cutoff score=10.4min). Results: Results showed that the AD+PF group were sleepier than the AD−PF group by subjective and objective measures, despite similarities in nocturnal sleep. The AD+PF group had higher scores on the Epworth Sleepiness Scale (8.5 versus 3.9, p =.001). The AD+PF group also had higher percentage of participants that had “Sleepy” MSLT scores compared to the AD−PF group (75% versus 31.6%, respectively; χ 2 =6.56, p =.01). Conclusions: The presence of parkinsonian features may be an independent risk factor for sleepiness in mild AD. [Copyright &y& Elsevier]

Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker. [ABSTRACT FROM AUTHOR]

Background. Identifying mobility disability risk factors may facilitate development of interventions promoting functional independence in older persons. We tested the hypothesis that musculoskeletal pain is associated with first occurrence of severe mobility disability. Methods. In a prospective observational study at 40 community-based sites, 759 older Catholic clergy in the Rush Religious Orders Study without baseline dementia, stroke, Parkinson's disease, or severe performance-based mobility disability (defined as gait speed less than or equal to 0.4 m/s) and at least one follow-up mobility evaluation were evaluated over a mean of 8.5 (SD = 3.8) years. All participants were queried about musculoskeletal pain in the year before baseline and underwent annual assessment of mobility. Results. Using a proportional hazards model adjusted for age, sex, and education, the hazard for incident severe mobility disability was greater for participants reporting pain in the year before baseline (odds ratio = 1.47, 95% confidence interval = 1.17–1.85). Results were unchanged after adjusting for self-reported mobility disability, gait speed, depressive symptoms, body mass index, physical activity, chronic medical conditions, and analgesic use. Compared with no report of musculoskeletal pain, musculoskeletal pain in one or two areas was associated with a 30% greater hazard for incident disability (odds ratio = 1.31, 95% confidence interval = 1.00–1.70). Musculoskeletal pain in three or more areas was associated with an 80% greater hazard for incident disability (odds ratio = 1.80, 95% confidence interval = 1.31–2.47). In participants without baseline self-reported mobility disability (n = 486), musculoskeletal pain was associated with greater hazard for incident self-reported mobility disability (odds ratio = 1.38, 95% confidence interval = 1.11–1.73). Conclusion. In older persons, musculoskeletal pain is associated with incident mobility disability. [ABSTRACT FROM PUBLISHER]

A 45-year-old man presented with vertebral collapse at L5 as an initial manifestation of multiple myeloma and underwent spinal fusion surgery using recombinant human bone morphogenetic protein-2 (rhBMP-2). Subsequent computed tomography (CT) scans and X-rays revealed heterotopic ossification of the left psoas muscle, pelvis, and anterior abdominal wall. While the occurrence of heterotopic ossification has previously been reported when rhBMP-2 has been used for spinal fusion surgery, this case demonstrates that it can occur to a much greater degree than previously seen. [ABSTRACT FROM AUTHOR]

Three systematic reviews in this issue have summarized evidence on brief cognitive tests to distinguish Alzheimer dementia from mild cognitive impairment or normal cognition, biomarker testing for neuropathologic Alzheimer disease, and prescription drugs and supplements in the treatment of Alzheimer dementia. The editorialists discuss the findings and hope for more options for preventing, diagnosing, and treating Alzheimer dementia. [ABSTRACT FROM AUTHOR]

This editorial comments on the article by O'Neill et al. in this issue. [ABSTRACT FROM AUTHOR]

Background. Factors contributing to gait difficulties in elderly persons are considered to be multifactorial and are not well understood. The purpose of this study was to examine the association of blood pressure (BP) with change in lower limb function in older persons. Methods. Eight hundred eighty-eight older Catholic clergy members without baseline dementia or Parkinson's disease were recruited from about 40 groups across the United States. At baseline, BP was measured, the presence of vascular diseases and diabetes was recorded, cognitive function was assessed, and medications were inspected. At baseline and subsequent annual visits, gait and balance were assessed using performance-based tasks from which a previously established composite measure of lower limb function was derived. Results. In a general estimating equation analysis controlling for age, education, and gender, a 10 mmHg increment in systolic blood pressure (SBP) was associated with greater decline in lower limb function (estimate of interaction = -6.35 x 10-3, standard error = 2.49 x 10-3, p=.011), Thus, on average, lower limb function declined 28.7% faster in persons with an SBP of 160 mmHg than in persons with an SBP of 120 mmHg. This effect was unchanged after controlling for baseline vascular diseases, diabetes, or cognition. However, censoring individuals who developed stroke during the study made the relationship between SBP and change in lower limb function nonsignificant. Conclusions. SBP may be associated with decline in lower limb function in older persons. [ABSTRACT FROM AUTHOR]

Interaction of ribose nucleotides with cobalt- and cadmium ferrocyanides was found maximum at neutral pH. Adsorption trend followed Langmuir isotherms. The Langmuir constants, Xm and KL were calculated. Purine nucleotides adsorbed more than pyrimidine nucleotides on both the metal ferrocyanides. Cobalt ferrocyanide was found a better adsorbent for all the ribose nucleotides studied. Infrared spectral studies of the adsorption adducts suggested that the adsorption occurs due to interaction of ribose nucleotide molecule with outer divalent metal ion present in the lattice of metal ferrocyanides. The results of the present study suggest that the metal ferrocyanides could have concentrated and stabilised the ribose nucleotides on their surface through adsorption processes during the course of chemical evolution. [Copyright &y& Elsevier]

Background: Cognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals. Methods: 19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke. Results: During a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants. Conclusions: These findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention. [ABSTRACT FROM AUTHOR]