Exploring the natural history of intrinsic capacity impairments: longitudinal patterns in the 10/66 study

Backgroundintrinsic capacity (IC) is a construct encompassing people’s physical and mental abilities. There is an implicit link amongst IC domains: cognition, locomotion, nutrition, sensory and psychological. However, little is known about the integration of the domains.Objectivesto investigate patterns in the presentation and evolution of IC domain impairments in low-and-middle-income countries and if such patterns were associated with adverse outcomes.Methodssecondary analyses of the first two waves of the 10/66 study (population-based surveys conducted in eight urban and four rural catchment areas in Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico and China). We applied latent transition analysis on IC to find latent statuses (latent clusters) of IC domain impairments. We evaluated the longitudinal association of the latent statuses with the risk of frailty, disability and mortality, and tested concurrent and predictive validity.Resultsamongst 14,923 participants included, the four latent statuses were: high IC (43%), low deterioration with impaired locomotion (17%), high deterioration without cognitive impairment (22%), and high deterioration with cognitive impairment (18%). A total of 61% of the participants worsened over time, 35% were stable, and 3% improved to a healthier status.Participants with deteriorated IC had a significantly higher risk of frailty, disability and dementia than people with high IC. There was strong concurrent and predictive validity. (Mortality Hazard Ratio = 4.60, 95%CI 4.16; 5.09; Harrel’s C = 0.73 (95%CI 0.72;0.74)).Conclusionshalf of the study population had high IC at baseline, and most participants followed a worsening trend. Four qualitatively different IC statuses or statuses were characterised by low and high levels of deterioration associated with their risk of disability and frailty. Locomotion and cognition impairments showed other trends than psychological and nutrition domains across the latent statuses

Effect of maturity and harvest season on antioxidant activity, phenolic compounds and ascorbic acid of Morinda citrifolia L. (noni) grown in Mexico (with track change)

Antioxidant activity diphenylpicrylhydrazyl (DPPH), the ferric-reducing antioxidant power assay (FRAP), nitric oxide (NO)], total polyphenols, phenolic compounds and ascorbic acid of Morinda citrifolia L. fruits were investigated as a function of maturity and three seasons patterns in Mexico. Maturity was evaluated in early, middle, sub-mature and mature stages (1 to 4) according to color and firmness. Significant differences were observed in the antioxidant activities and chemical composition of the fruits at different maturity and seasons. During February-March and May- June, fruits from middle and mature stages exhibited the highest antioxidant activities and total polyphenol content compared to other stages, while in November, ripe fruits reached the greatest antioxidant efficacy, total phenolic and ascorbic acid contents. Total polyphenols and ascorbic acid reached the highest amounts during May-June, although antioxidant activities were moderate compared to greater values in February-March or November depending upon maturity. The ability of M. citrifolia fruits to inhibit NO production by LPSactivated RAW 264.7 cells was quite comparable to or higher than N-nitro-L-arginine methyl ester (LNAME). This work shows that season and maturity stages have a profound effect on the antioxidant capacity, phenols and ascorbic acid of M. Citrifolia fruits.Keywords: Morinda citrifolia, diphenylpicrylhydrazyl (DPPH) radical scavenging, maturity, seasons, total polyphenol and phenolics compounds, reducing power, ascorbic acid, scavenging nitric oxide.African Journal of Biotechnology Vol. 12(29), pp. 4630-463

Burden of Parkinsonism and Parkinson\u27s Disease on Health Service Use and Outcomes in Latin America

\ua9 2023 - The authors. Published by IOS Press.Background: Little is known about the burden of parkinsonism and Parkinson\u27s disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. Objective: The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. Methods: 12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis. Results: At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries. Conclusions: Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services

Strange prospects for LHC energies

Strange quark and hadron production will be studied at the Large Hadron Collider (LHC) energies in order to explore the properties of both pp and heavy-ion collisions. The ALICE experiment will be specifically efficient in the strange sector with the identification of baryons and mesons over a wide range of transverse momentum. Dedicated measurements are proposed for investigating chemical equilibration and bulk properties. Strange particles can also help to probe kinematical regions where hard processes and pQCD dominate. We try to anticipate here several ALICE analyses to be performed as the first Pb--Pb and pp data will be available.Comment: 5 pages, 2 figures. To appear in the proceedings of Hot Quarks 2006, Villasimius, Italy, 15-20 May 200

An ultra scale-down methodology to characterize aspects of the response of human cells to processing by membrane separation operations

Tools that allow cost-effective screening of the susceptibility of cell lines to operating conditions which may apply during full scale processing are central to the rapid development of robust processes for cell-based therapies. In this paper, an ultra scale-down (USD) device has been developed for the characterization of the response of a human cell line to membrane-based processing, using just a small quantity of cells that is often all that is available at the early discovery stage. The cell line used to develop the measurements was a clinically relevant human fibroblast cell line. The impact was evaluated by cell damage on completion of membrane processing as assessed by trypan blue exclusion and release of intracellular lactate dehydrogenase (LDH). Similar insight was gained from both methods and this allowed the extension of the use of the LDH measurements to examine cell damage as it occurs during processing by a combination of LDH appearance in the permeate and mass balancing of the overall operation. Transmission of LDH was investigated with time of operation and for the two disc speeds investigated (6,000 and 10,000 rpm or ϵmax  ≈ 1.9 and 13.5 W mL-1 , respectively). As expected, increased energy dissipation rate led to increased transmission as well as significant increases in rate and extent of cell damage. The method developed can be used to test the impact of varying operating conditions and cell lines on cell damage and morphological changes. Biotechnol. Bioeng. 2017;114: 1241-1251. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc

Prevalence and Incidence of Parkinson\u27s Disease in Latin America: A Meta-Analysis

\ua9 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. Background: Parkinson\u27s disease (PD) is a rapidly growing neurodegenerative disorder, but up-to-date epidemiological data are lacking in Latin America. We sought to estimate the prevalence and incidence of PD and parkinsonism in Latin America. Methods: We searched Medline, Embase, Scopus, Web of Science, Scientific Electronic Library Online, and Literatura Latino-Americana e do Caribe em Ci\ueancias da Sa\ufade or the Latin American and Caribbean Health Science Literature databases for epidemiological studies reporting the prevalence or incidence of PD or parkinsonism in Latin America from their inception to 2022. Quality of studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Data were pooled via random-effects meta-analysis and analyzed by data source (cohort studies or administrative databases), sex, and age group. Significant differences between groups were determined by meta-regression. Results: Eighteen studies from 13 Latin American countries were included in the review. Meta-analyses of 17 studies (nearly 4 million participants) found a prevalence of 472 (95% CI, 271–820) per 100,000 and three studies an incidence of 31 (95% CI, 23–40) per 100,000 person-years for PD; and seven studies found a prevalence of 4300 (95% CI, 1863–9613) per 100,000 for parkinsonism. The prevalence of PD differed by data source (cohort studies, 733 [95% CI, 427–1255] vs. administrative databases. 114 [95% CI, 63–209] per 100,000, P < 0.01), age group (P < 0.01), but not sex (P = 0.73). PD prevalence in ≥60 years also differed significantly by data source (cohort studies. 1229 [95% CI, 741–2032] vs. administrative databases, 593 [95% CI, 480–733] per 100,000, P < 0.01). Similar patterns were observed for parkinsonism. Conclusions: The overall prevalence and incidence of PD in Latin America were estimated. PD prevalence differed significantly by the data source and age, but not sex. \ua9 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition

Introduction Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage. Methods Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n = 333, 73 ± 7 years; CSF n = 149, 72 ± 6 years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership, and Framingham Stroke Risk Profile. Results Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models. Discussion Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI

Joint data imputation and mechanistic modelling for simulating heart-brain interactions in incomplete datasets

The use of mechanistic models in clinical studies is limited by the lack of multi-modal patients data representing different anatomical and physiological processes. For example, neuroimaging datasets do not provide a sufficient representation of heart features for the modeling of cardiovascular factors in brain disorders. To tackle this problem we introduce a probabilistic framework for joint cardiac data imputation and personalisation of cardiovascular mechanistic models, with application to brain studies with incomplete heart data. Our approach is based on a variational framework for the joint inference of an imputation model of cardiac information from the available features, along with a Gaussian Process emulator that can faithfully reproduce personalised cardiovascular dynamics. Experimental results on UK Biobank show that our model allows accurate imputation of missing cardiac features in datasets containing minimal heart information, e.g. systolic and diastolic blood pressures only, while jointly estimating the emulated parameters of the lumped model. This allows a novel exploration of the heart-brain joint relationship through simulation of realistic cardiac dynamics corresponding to different conditions of brain anatomy

Mild Cognitive Impairment Staging Yields Genetic Susceptibility, Biomarker, and Neuroimaging Differences

INTRODUCTION: While Alzheimer’s disease (AD) is divided into severity stages, mild cognitive impairment (MCI) remains a solitary construct despite clinical and prognostic heterogeneity. This study aimed to characterize differences in genetic, cerebrospinal fluid (CSF), neuroimaging, and neuropsychological markers across clinician-derived MCI stages. METHODS: Vanderbilt Memory & Aging Project participants with MCI were categorized into 3 severity subtypes at screening based on neuropsychological assessment, functional assessment, and Clinical Dementia Rating interview, including mild (n = 18, 75 ± 8 years), moderate (n = 89 72 ± 7 years), and severe subtypes (n = 18, 78 ± 8 years). At enrollment, participants underwent neuropsychological testing, 3T brain magnetic resonance imaging (MRI), and optional fasting lumbar puncture to obtain CSF. Neuropsychological testing and MRI were repeated at 18-months, 3-years, and 5-years with a mean follow-up time of 3.3 years. Ordinary least square regressions examined cross-sectional associations between MCI severity and apolipoprotein E (APOE)-ε4 status, CSF biomarkers of amyloid beta (Aβ), phosphorylated tau, total tau, and synaptic dysfunction (neurogranin), baseline neuroimaging biomarkers, and baseline neuropsychological performance. Longitudinal associations between baseline MCI severity and neuroimaging and neuropsychological trajectory were assessed using linear mixed effects models with random intercepts and slopes and a follow-up time interaction. Analyses adjusted for baseline age, sex, race/ethnicity, education, and intracranial volume for MRI models. RESULTS: Stages differed at baseline on APOE-ε4 status (early middle = late), phosphorylated and total tau (early = middle < late; p-values < 0.05), and neurogranin concentrations (early = middle < late; p-values < 0.05). MCI stage related to greater longitudinal cognitive decline, hippocampal atrophy, and inferior lateral ventricle dilation (early < late; p-values < 0.03). DISCUSSION: Clinician staging of MCI severity yielded longitudinal cognitive trajectory and structural neuroimaging differences in regions susceptible to AD neuropathology and neurodegeneration. As expected, participants with more severe MCI symptoms at study entry had greater cognitive decline and gray matter atrophy over time. Differences are likely attributable to baseline differences in amyloidosis, tau, and synaptic dysfunction. MCI staging may provide insight into underlying pathology, prognosis, and therapeutic targets