CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma.

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.

Secreted Protein Profiling of Human Aortic Smooth Muscle Cells Identifies Vascular Disease Associations.

BACKGROUND: Smooth muscle cells (SMCs), which make up the medial layer of arteries, are key cell types involved in cardiovascular disease, the leading cause of mortality and morbidity worldwide. In response to microenvironment alterations, SMCs dedifferentiate from a contractile to a synthetic phenotype characterized by an increased proliferation, migration, production of ECM (extracellular matrix) components, and decreased expression of SMC-specific contractile markers. These phenotypic changes result in vascular remodeling and contribute to the pathogenesis of cardiovascular disease, including coronary artery disease, stroke, hypertension, and aortic aneurysms. Here, we aim to identify the genetic variants that regulate ECM secretion in SMCs and predict the causal proteins associated with vascular disease-related loci identified in genome-wide association studies. METHODS: Using human aortic SMCs from 123 multiancestry healthy heart transplant donors, we collected the serum-free media in which the cells were cultured for 24 hours and conducted liquid chromatography-tandem mass spectrometry-based proteomic analysis of the conditioned media. RESULTS: We measured the abundance of 270 ECM and related proteins. Next, we performed protein quantitative trait locus mapping and identified 20 loci associated with secreted protein abundance in SMCs. We functionally annotated these loci using a colocalization approach. This approach prioritized the genetic variant rs6739323-A at the 2p22.3 locus, which is associated with lower expression of LTBP1 (latent-transforming growth factor beta-binding protein 1) in SMCs and atherosclerosis-prone areas of the aorta, and increased risk for SMC calcification. We found that LTBP1 expression is abundant in SMCs, and its expression at mRNA and protein levels was reduced in unstable and advanced atherosclerotic plaque lesions. CONCLUSIONS: Our results unravel the SMC proteome signature associated with vascular disorders, which may help identify potential therapeutic targets to accelerate the pathway to translation.

Polygenic Risk Score Associates With Atherosclerotic Plaque Characteristics at Autopsy.

BACKGROUND: Polygenic risk scores (PRSs) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically. METHODS: From 4327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner for sudden death between 1994 and 2015, 2455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas, and thrombotic CAD. RESULTS: After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age, 48.8±14.7 years; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared with subjects in the lowest quintile, with greater %stenosis (80.3%±27.0% versus 50.4%±38.7%; adjusted P<0.001) and a higher frequency of calcification (69.6% versus 35.8%; adjusted P=0.004) and thin-cap fibroatheroma (26.7% versus 9.5%; adjusted P=0.007). Even after adjustment for traditional CAD risk factors, subjects within the highest PRS quintile had higher odds of severe atherosclerosis (ie, ≥75% stenosis; adjusted odds ratio, 3.77 [95% CI, 2.10-6.78]; P<0.001) and plaque rupture (adjusted odds ratio, 4.05 [95% CI, 2.26-7.24]; P<0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged ≤50 years (adjusted odds ratio, 4.08 [95% CI, 2.01-8.30]; P<0.001). No statistically significant associations were observed with plaque erosion after adjusting for covariates. CONCLUSIONS: This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects.

Perceived Stress, Blood Biomarkers, and Cognitive Functioning in Older Adults.

INTRODUCTION: There is a substantial gap in knowledge regarding how perceived stress may influence the relationship between serum-measured biomarkers for Alzheimer's disease and cognitive decline. METHODS: This study consists of 1118 older adult participants from the Chicago Health and Aging Project (CHAP) (60% Black participants and 63% female participants). Linear mixed effects regression models were conducted to examine the role of perceived stress in the association between three blood biomarkers: total tau (t-tau), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL) on global cognitive decline. Stratified analysis by stress level was also conducted to evaluate the associations between each blood biomarker and baseline cognitive function and decline. All models adjusted for age, race, sex, education, time, and their interactions with time. RESULTS: The interaction of stress, NfL concentration, and time was statistically significant on global cognition ( ß = -0.064 [SE = 0.028], p = .023) and on episodic memory ( ß = -0.097 [SE = 0.036], p = .007). CONCLUSIONS: Greater stress level worsens the association between high NfL concentration and cognitive decline. Stress management interventions may be helpful to reduce the rate of cognitive decline in individuals with high concentrations of NfL.

Clonal Proliferation Within Smooth Muscle Cells in Unstable Human Atherosclerotic Lesions.

BACKGROUND: Studies in humans and mice using the expression of an X-linked gene or lineage tracing, respectively, have suggested that clones of smooth muscle cells (SMCs) exist in human atherosclerotic lesions but are limited by either spatial resolution or translatability of the model. METHODS: Phenotypic clonality can be detected by X-chromosome inactivation patterns. We investigated whether clones of SMCs exist in unstable human atheroma using RNA in situ hybridization (BaseScope) to identify a naturally occurring 24-nucleotide deletion in the 3'UTR of the X-linked BGN (biglycan) gene, a proteoglycan highly expressed by SMCs. BGN-specific BaseScope probes were designed to target the wild-type or deletion mRNA. Three different coronary artery plaque types (erosion, rupture, and adaptive intimal thickening) were selected from heterozygous females for the deletion BGN. Hybridization of target RNA-specific probes was used to visualize the spatial distribution of mutants. A clonality index was calculated from the percentage of each probe in each region of interest. Spatial transcriptomics were used to identify differentially expressed transcripts within clonal and nonclonal regions. RESULTS: Less than one-half of regions of interest in the intimal plaque were considered clonal with the mean percent regions of interest with clonality higher in the intimal plaque than in the media. This was consistent for all plaque types. The relationship of the dominant clone in the intimal plaque and media showed significant concordance. In comparison with the nonclonal lesions, the regions with SMC clonality had lower expression of genes encoding cell growth suppressors such as CD74, SERF-2 (small EDRK-rich factor 2), CTSB (cathepsin B), and HLA-DPA1 (major histocompatibility complex, class II, DP alpha 1), among others. CONCLUSIONS: Our novel approach to examine clonality suggests atherosclerosis is primarily a disease of polyclonally and to a lesser extent clonally expanded SMCs and may have implications for the development of antiatherosclerotic therapies.

The fluorosis conundrum: bridging the gap between science and public health.

Fluorosis, a chronic condition brought on by excessive fluoride ingestion which, has drawn much scientific attention and public health concern. It is a complex and multifaceted issue that affects millions of people worldwide. Despite decades of scientific research elucidating the causes, mechanisms, and prevention strategies for fluorosis, there remains a significant gap between scientific understanding and public health implementation. While the scientific community has made significant strides in understanding the etiology and prevention of fluorosis, effectively translating this knowledge into public health policies and practices remains challenging. This review explores the gap between scientific research on fluorosis and its practical implementation in public health initiatives. It suggests developing evidence-based guidelines for fluoride exposure and recommends comprehensive educational campaigns targeting the public and healthcare providers. Furthermore, it emphasizes the need for further research to fill the existing knowledge gaps and promote evidence-based decision-making. By fostering collaboration, communication, and evidence-based practices, policymakers, healthcare professionals, and the public can work together to implement preventive measures and mitigate the burden of fluorosis on affected communities. This review highlighted several vital strategies to bridge the gap between science and public health in the context of fluorosis. It emphasizes the importance of translating scientific evidence into actionable guidelines, raising public awareness about fluoride consumption, and promoting preventive measures at individual and community levels.

Establishment of Age Specific Reference Interval for Aminoacids and Acylcarnitine in Dried Blood Spot by Tandem Mass Spectrometry.

The Extended Screening for Inborn Errors of Metabolism is done for aminoacidopathies, fatty acid oxidation disorders and organic acid disorders. In a single dried blood spot, the tandem mass spectrometry is capable of measuring multiple analytes like amino acids, acylcarnitines, nucleosides, succinylacetone and lysophosphatidylcholines. This study was proposed to establish age specific reference internal for aminoacids and acylcartinitine in dried blood spot by tandem mass spectrometry. A total of 480 apparently healthy children were enrolled for the study and sub classified into four groups as follows: Group A: 0-1 month, Group B: 1 month-1 year, Group C: 1-5 year and Group D: 5-12 years each having 120 participants. Sample size were calculated as per CLSI approved guidelines. Tables 1 and 2 presents the age-specific percentile distribution of aminoacids and acylcarnitines established from healthy subjects as per rank-based method recommended by the IFCC and CLSI. Tables 3, 4 and 5 presents the cut-off values of primary and secondary marker/ratios for screening of aminoacidopathies, fatty acid oxidation disorders and organic acid disorders respectively. As a general principle, the interpretation of extended newborn screening results should be based on age specific cut-off established by the laboratory for primary analyte concentration and secondary analyte concentration/ ratios. This study was useful in establishing age specific cut-off values for various amino acids and acylcarnitines in South Indian population. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text].

Relationships between neighborhood disadvantage and cardiovascular findings at autopsy in subjects with sudden death.

BACKGROUND: Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland. METHODS: State of Maryland investigation reports from 2,278 subjects within the CVPath Sudden Death Registry were screened for street addresses and 9-digit zip codes. Area deprivation index (ADI), used as metric for neighborhood disadvantage, was available for 1,464 subjects; 650 of whom self-identified as Black and 814 as White. The primary study outcome measurements were causes of death and gross and histopathologic findings of the heart. RESULTS: Subjects from most disadvantaged neighborhoods (i.e., ADI ≥ 8; n = 607) died at younger age compared with subjects from less disadvantaged neighborhoods (i.e., ADI ≤ 7; n = 857; 46.07 ± 14.10 vs 47.78 ± 13.86 years; P = 0.02) and were more likely Black or women. They were less likely to die from cardiac causes of death (61.8% vs 67.7%; P = 0.02) and had less severe atherosclerotic plaque features, including plaque burden, calcification, intraplaque hemorrhage, and thin-cap fibroatheromas. In addition, subjects from most disadvantaged neighborhoods had lower frequencies of plaque rupture (18.8% vs 25.1%, P = 0.004). However, these associations were omitted after adjustment for traditional risk factors and race. CONCLUSION: Neighborhood disadvantage did not associate with cause of death or coronary histopathology after adjustment for cardiovascular risk factors and race, implying that social determinants of health other than neighborhood disadvantage play a more prominent role in sudden cardiac death.

Race and Apolipoprotein E-e4 Allele Status Differences in the Association Between Loneliness and Cognitive Decline.

OBJECTIVE: This study aimed to examine race and apolipoprotein E-e4 allele (APOE-e4) status differences in the longitudinal associations between loneliness and cognitive decline. METHODS: The study sample is composed of participants ( N = 7696, 64% Black participants and 36% White participants) from the Chicago Health and Aging Project, a population-based cohort study. Mixed-effects regression models were conducted to examine the longitudinal associations between loneliness on global cognitive function and individual tests of cognitive function. Models were also stratified by race and APOE-e4. RESULTS: A greater percentage of Black participants (17%) reported loneliness at baseline visit compared with White participants (12%). Black and White participants who were lonely individuals had a similar rate of decline in global cognitive function at 0.075 (95% confidence interval [CI] = -0.082 to -0.068) standard deviation unit (SDU) per year for Black participants and at 0.075 (95% CI = -0.086 to -0.063) SDU per year for White participants. Lonely participants with APOE-e4 had a higher rate of global cognitive decline at -0.102 (95% CI = -0.115 to -0.088) SDU per year than for lonely participants without APOE-e4 at -0.052 (95% CI = -0.059 to -0.045) SDU per year. CONCLUSIONS: The burden of loneliness and its relation to cognitive decline is higher among participants with APOE-e4 compared with those without APOE-e4. Loneliness is associated with cognitive decline in both Black and White participants.

Retinal Changes in Parkinson's Disease: A Non-invasive Biomarker for Early Diagnosis.

Parkinson's disease (PD) is caused due to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) which leads to the depletion of dopamine in the body. The lack of dopamine is mainly due to aggregation of misfolded α-synuclein which causes motor impairment in PD. Dopamine is also required for normal retinal function and the light-dark vision cycle. Misfolded α-synuclein present in inner retinal layers causes vision-associated problems in PD patients. Hence, individuals with PD also experience structural and functional changes in the retina. Mutation in LRRK2, PARK2, PARK7, PINK1, or SNCA genes and mitochondria dysfunction also play a role in the pathophysiology of PD. In this review, we discussed the different etiologies which lead to PD and future prospects of employing non-invasive techniques and retinal changes to diagnose the onset of PD earlier.

Cognitive Activity Is Associated with Cognitive Function over Time in a Diverse Group of Older Adults, Independent of Baseline Biomarkers.

BACKGROUND: More frequent engagement in cognitive activity is associated with better cognitive function in older adults, but the mechanism of action is not fully understood. Debate remains whether increased cognitive activity provides a meaningful benefit for cognitive health or if decreased cognitive activity represents a prodrome of cognitive impairment. Neurological biomarkers provide a novel way to examine this relationship in the context of cognitive aging. METHODS: We examined the association of self-reported cognitive activity, cognitive function, and concentrations of three biomarkers in community-dwelling participants of a longitudinal, population-based study. Cognitive activity was measured at baseline by asking participants to rate the frequency of 7 activities: (1) viewing television, (2) listening to the radio, (3) visiting a museum, (4) playing games, such as cards, checkers, crosswords, or other puzzles or games, (5) reading books, (6) reading magazines, and (7) reading newspapers. Cognitive function was measured with a battery of four tests (Mini-Mental State Examination, Digit Symbol Test, and the immediate and delayed recall of the East Boston Test) averaged into a composite score. At baseline, we evaluated the concentration of total tau (tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). RESULTS: The study sample comprised 1,168 older participants, primarily non-Hispanic Blacks (60%) and women (63%). At baseline, they were an average of 77 years old with 12.6 years of education. Mixed-effects models showed that cognitive activity was associated with better cognitive functioning at baseline and over time. These relationships remained after each biomarker was added to the model. Over an average of 6.4 years of follow-up, cognitive activity was associated with cognitive decline in the model with tau (estimate = 0.0123; p value = 0.03) and was mildly attenuated in the models with NfL (estimate = 0.0110; p value = 0.06) and GFAP (estimate = 0.0111; p value = 0.06). Biomarkers did not modify the association between cognitive activity and cognitive function over time. CONCLUSION: The benefits of cognitive activity on cognition appear to be independent of biomarkers: tau, NfL, and GFAP, measured at baseline. More frequent cognitive activity may benefit the cognitive health of older adults with a wide range of potential disease risk and presentations.

CdSe Quantum Dots Bedecked on ZnO/TiO2/CuO Ternary Nanocomposite for Enhanced Photocatalytic and Photovoltaic Applications.

Herein, we synthesized a CdSe quantum dots (QDs)-decorated ternary metal oxide nanocomposite of ZnO/TiO2/CuO through a simple hydrothermal method. The prepared nanocomposite exhibited monoclinic, hexagonal, and cubic phase structures in XRD (X-ray diffraction) analysis. UV-vis absorbance spectra showed the broad absorption spectrum. SEM (scanning electron microscopy) clearly showed the presence of nanoparticles and confirmed the elements through elemental mapping. TEM (transmission electron microscopy) confirmed the nanostructure of metal oxides decorated with QDs. The average particle size was 45 nm for metal oxides and 7 nm for QDs. XPS (X-ray photoelectron spectroscopy) also confirmed the surface elemental composition. The prepared nanocomposites were introduced as photoanodes in DSSCs (dye-sensitized solar cells) and as photocatalysts for industrial dye solution. Among these samples, CdSe@CuO/TiO2/ZnO showed an improved performance of PCE (photon conversion efficiency) of 3.68% in DSSC and 96% photocatalytic degradation efficiency. It showed a recycling efficiency of ∼92% after 4 cycles against methylene blue (MB) organic dye under visible light irradiation.

Serum neurofilament light chain, brain infarcts, and the risk of stroke: a prospective population-based cohort study.

Neurofilament light chain (NfL), a neuron-specific protein, has been related to several neurodegenerative diseases. In addition, elevated levels of NfL have also been observed in patients admitted to the hospital for stroke, suggesting that NfL as a biomarker may extend well beyond neurodegenerative diseases. Therefore, using data from the Chicago Health and Aging Project (CHAP), a population-based cohort study, we prospectively investigated the association of serum NfL levels with incident stroke and brain infarcts. During a follow-up of 3603 person-years, 133 (16.3%) individuals developed incident stroke, including ischemic and hemorrhagic. The HR (95%CI) of incident stroke was 1.28 (95%CI 1.10-1.50) per 1 standard deviation (SD) increase of log10 NfL serum levels. Compared to participants in the first tertile of NfL (i.e., lower levels), the risk of stroke was 1.68 times higher (95%CI 1.07-2.65) in those in the second tertile and 2.35 times higher (95%CI 1.45-3.81) in those in the third tertile of NfL. NfL levels were also positively associated with brain infarcts; 1-SD in log10 NfL levels was associated with 1.32 (95%CI 1.06-1.66) higher odds of one or more brain infarcts. These results suggest that NfL may serve as a biomarker of stroke in older adults.

Molecular dynamics articulated multilevel virtual screening protocol to discover novel dual PPAR α/γ agonists for anti-diabetic and metabolic applications.

PPARα and PPARγ are isoforms of the nuclear receptor superfamily which regulate glucose and lipid metabolism. Activation of PPARα and PPARγ receptors by exogenous ligands could transactivate the expression of PPARα and PPARγ-dependent genes, and thereby, metabolic pathways get triggered, which are helpful to ameliorate treatment for the type 2 diabetes mellitus, and related metabolic complications. Herein, by understanding the structural requirements for ligands to activate PPARα and PPARγ proteins, we developed a multilevel in silico-based virtual screening protocol to identify novel chemical scaffolds and further design and synthesize two distinct series of glitazone derivatives with advantages over the classical PPARα and PPARγ agonists. Moreover, the synthesized compounds were biologically evaluated for PPARα and PPARγ transactivation potency from nuclear extracts of 3T3-L1 cell. Furthermore, glucose uptake assay on L6 cells confirmed the potency of the synthesized compounds toward glucose regulation. Percentage lipid-lowering potency was also assessed through triglyceride estimate from 3T3-L1 cell extracts. Results suggested the ligand binding mode was in orthosteric fashion as similar to classical agonists. Thus molecular docking and molecular dynamics (MD) simulation experiments were executed to validate our hypothesis on mode of ligands binding and protein complex stability. Altogether, the present study developed a newer protocol for virtual screening and enables to design of novel glitazones for activation of PPARα and PPARγ-mediated pathways. Accordingly, present approach will offer benefit as a therapeutic strategy against type 2 diabetes mellitus and associated metabolic complications.

Identification of phytochemical as a dual inhibitor of PI3K and mTOR: a structure-based computational approach.

Breast cancer is a common form of cancer that affects both men and women. One of the most common types of genomic flaws in cancer is the aberrations in the PI3K/AKT/mTOR pathway. The benefit of dual targeting PI3K as well as mTOR is that the kinase-positive feedback loops are more effectively inhibited. Therefore, in the current study, structure-based models like molecular docking, MM-GBSA, Qikprop, induced fit docking, simulated molecular dynamics (MD), and thermal MM-GBSA were used to identify the phytochemicals from the zinc 15 database, which may inhibit PI3K and mTOR. After docking the phytochemicals with PI3K (PDB 4FA6), ten ligands based on the docking score were selected, among which salvianolic acid C had the highest docking score. Hence, salvianolic acid A was also docked. All the ligands taken showed a binding energy of greater than - 30 kcal/mol. The predicted ADME showed that the ligands have druggable properties. By performing MD of the top five ligands and salvianolic acid A, it was found that ZINC000059728582, ZINC000257545754, ZINC000253532301, and salvianolic acid A form a stable complex with PI3K protein, among which ZINC000014690026 showed interaction with Val 882 for more than 89% of the time. Salvianolic acid A is already proven to suppress tumor growth in acute myeloid leukemia by inhibiting PI3K/AKT pathway, but the exact protein target is unknown. Therefore, the present study identifies new molecules and provides evidence for salvianolic acid A for dual inhibition. Further experiments must be performed both in vitro and in vivo to support the predictions of these computational tools.

Neuroticism, physical activity, and cognitive functioning in a population-based cohort of older adults.

BACKGROUND: Little is known about how physical activity influences the relationship between neuroticism and cognitive function and cognitive decline. METHODS: Data from the Chicago Health and Aging Project (CHAP) was utilized to conduct this study. CHAP is a population-based cohort study of chronic conditions in older adults. Participants completed in-home interviews cycles of three years from 1993-2012. Mixed effects regression models were conducted to test the associations between physical activity, neuroticism, and the interaction between neuroticism and physical activity on outcomes: global cognitive function, global cognitive decline, episodic memory, decline in episodic memory, perceptual speed, and decline in perceptual speed. Stratified mixed effects regression models by physical activity level were conducted to test the associations between neuroticism and global cognitive function and global cognitive decline. RESULTS: A total of 7,685 participants were eligible for this study. Participants were 62% female and 64% African American. We found statistically significant associations for the interaction of high physical activity and neuroticism on baseline global cognitive function (ß = 0.017 (SE = 0.007), p = .010) and on the interaction of neuroticism and high physical activity on baseline episodic memory (ß = 0.020 (SE = .009), p = .021) and on decline in episodic memory over time (ß = -0.003 (SE = .001), p = .039). CONCLUSION: Higher physical activity lessened the association between higher neuroticism and poor cognitive outcomes.

Fibrocartilaginous mesenchymoma of pelvis-a potential diagnostic pitfall.

Fibrocartilaginous mesenchymoma (FM) is a rare bone tumor mimicking other fibrocartilaginous lesions on imaging and histologically. Hence, it is difficult to diagnose this entity especially on small biopsies. In this article, we report a case of FM mimicking desmoplastic fibroma on biopsy. A 36-year-old male presented with pain in the left hip. Imaging showed a large expansile lytic lesion involving the acetabulum and pubis. The differential diagnosis was suggestive of giant cell tumor, aneurysmal bone cyst, intraosseous desmoplastic fibroma, and chondrosarcoma. Biopsy revealed a low-grade spindle cell lesion with no evidence of osteoid or chondroid matrix. The lack of cartilaginous nodules in the biopsy prompted a preoperative diagnosis of desmoplastic fibroma. The excised mass showed bland spindle cell proliferation, benign cartilage nodules, and epiphyseal plate-like enchondral ossification suggestive of fibrocartilaginous mesenchymoma. Negative immunostaining for SATB2, CDK4, and MDM2 ruled out low-grade central osteosarcoma. Though GNAS mutations were not performed in this case, rimming of the bony trabeculae at the periphery of the epiphyseal growth plate-like cartilaginous nodule ruled out fibrous dysplasia. The absence of cartilaginous component misleads the diagnosis preoperatively in small biopsies.

Optical, emission, and excitation dynamics of Eu3+ -doped bismuth-based phosphate glass for visible display laser applications.

Eu3+ -doped-bismuth-based phosphate glasses with chemical equation (60 - x)P2 O5 -20Bi2 O3 -10Na2 CO3 -10SrF2 -xEu2 O3 (PBNSEu), (where x = 0, 0.1, 0.5, 1.0, 1.5 and 2 mol%) were fabricated using the melt-quenching method. Obtain X-ray diffraction (XRD), energy-dispersive X-ray (EDAX), and Fourier transform infrared (FTIR) spectra were used to characterize the structure of the prepared PBNSEu glass. The J-O (Judd-Ofelt) intensity parameters (Ω2 , Ω4 ) were estimated using photoluminescence emission spectra. When excited with a xenon lamp at λexc  = 394 nm, the most intense red-emission transition occurred at ~612 nm (5 D0 →7 F2 ). J-O intensity parameters were used to calculate radiative properties, whereas the radiative branching ratio (ßR ), radiative transition probability (AR ), radiative lifetime (τR ), and total radiative transition rate (Aτ ) were calculated for the transitions 5 D0 →7 FJ (where J = 0-4) and were obtained in the emission spectra for europium ion-doped in the current glass. Using the CIE1931 chromaticity coordinates axes, the colours of various concentrations of Eu3+ ion-doped PBNS glass were evaluated using the emission spectra. Temperature-dependent luminescence spectra were recorded for the optimized PBNSEu20 glass to calculate the activation energy. These results strongly suggested red components in w-LEDs and visible display laser applications.

Approaches to engage an aging, rural cohort in southern India during the COVID-19 crisis and the psychological impact of COVID-19 in this cohort.

INTRODUCTION: The COVID-19 pandemic produced an unprecedented crisis across the world. Long-term cohort studies were stalled, including our longitudinal aging cohort study in rural India. METHODS: We describe approaches undertaken to engage with our cohort (n = 1830) through multiple rounds of calls and how we provided useful services to our subjects during the lockdown period. Consenting subjects also underwent telephonic assessments for depression and anxiety using validated, self-report questionnaires. RESULTS: Subjects reported benefitting from our telephonic engagement strategies, including the COVID-related safety awareness and counselling service. The proportion of subjects with depression increased from 7.42% pre-COVID to 28.97% post-COVID. DISCUSSION: We envisage that such engagement strategies would improve subject rapport and cohort retention, and thus, could be adopted by similar cohort studies across the world. This marginalized, rural Indian community had severe, adverse psychological impact in this pandemic. Urgent public health measures are needed to mitigate this impact and develop appropriate preventive strategies.

Prevalence of Alzheimer's disease dementia in the 50 US states and 3142 counties: A population estimate using the 2020 bridged-race postcensal from the National Center for Health Statistics.

INTRODUCTION: This study estimates the prevalence and number of people living with Alzheimer's disease (AD) dementia in 50 US states and 3142 counties. METHODS: We used cognitive data from the Chicago Health and Aging Project, a population-based study, and combined it with the National Center for Health Statistics 2020 bridged-race population estimates to determine the prevalence of AD in adults ≥65 years. RESULTS: A higher prevalence of AD was estimated in the east and southeastern regions of the United States, with the highest in Maryland (12.9%), New York (12.7%), and Mississippi (12.5%). US states with the highest number of people with AD were California, Florida, and Texas. Among larger counties, those with the highest prevalence of AD were Miami-Dade County in Florida, Baltimore city in Maryland, and Bronx County in New York. DISCUSSION: The state- and county-specific estimates could help public health officials develop region-specific strategies for caring for people with AD.