Growth Differentiation Factor 15 and Diet Quality Trajectory Interact to Determine Frailty Incidence among Middle-Aged Urban Adults.

BACKGROUND: Elevated plasma growth differentiation factor 15 (GDF15) and poor diet quality may be associated with increased frailty incidence, although their interactive associations have not been assessed in urban middle-aged adults. OBJECTIVES: We aimed to examine GDF15 and its interactive association with diet quality in relation to frailty incidence among a sample of middle-aged urban adults. METHODS: The relationship between GDF15 and diet quality trajectories in relation to incident frailty was examined in a longitudinal study of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (2004-2017). Serum GDF15 concentration and frailty incidence were primary exposure and outcome, respectively. Group-based trajectory models were used to assess diet quality trajectories (≤3 visits/participant, N = 945, N' = 2247 observations) using the Healthy Eating Index 2010 version (HEI-2010), Dietary Inflammatory Index, and mean adequacy ratio (MAR). Cox proportional hazards models were used, testing interactive associations of GDF15 and diet quality trajectories with frail/prefrail incidence (N = 400 frailty-free at first visit, N' = 604 observations, n = 168 incident frail/prefrail). RESULTS: Both elevated GDF15 and lower diet quality trajectories were associated with a lower probability of remaining nonfrail (≤13 y follow-up). Among females, the "high diet quality" HEI-2010 trajectory had a hazard ratio (HR) of 0.15 [95% confidence interval (CI): 0.04, 0.54; P = 0.004; fully adjusted model] when compared with the "low diet quality" trajectory group. Among males only, there was an antagonistic interaction between lower HEI-2010 trajectory and elevated GDF15. Specifically, the HR for GDF15-frailty in the higher diet quality trajectory group (high/medium combined), and among males, was 2.69 (95% CI: 1.06, 6.62; P = 0.032), whereas among the lower diet quality trajectory group, the HR was 0.94 (95% CI: 0.49, 1.80; P = 0.86). Elevated GDF15 was independently associated with frailty among African American adults. CONCLUSIONS: Pending replication, we found an antagonistic interaction between GDF15 and HEI-2010 trajectory in relation to frailty incidence among males.

Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study.

BACKGROUND: The study examined how plasma proteome indicators may explain the link between poor cardiovascular health (CVH) and dementia risk. METHODS: The present study involved 28,974 UK Biobank participants aged 50-74y at baseline (2006-2010) who were followed-up for ≤ 15 y for incidence of dementia. CVH was calculated using Life's Essential 8 (LE8) total scores. The scores were standardized and reverse coded to reflect poor CVH (LE8z_rev). OLINK proteomics was available on this sample (k = 1,463 plasma proteins). The study primarily tested the mediating effects of the plasma proteome in LE8z_rev-dementia effect. The total effect was decomposed into "mediation only" or pure indirect effect (PIE), "interaction only" or interaction referent (INTREF), "neither mediation nor interaction" or controlled direct effect (CDE), and "both mediation and interaction" or mediated interaction (INTMED). RESULTS: The study found poorer CVH assessed by LE8z_rev increased the risk of all-cause dementia by 11 % [per 1 SD, hazard ratio, (HR) = 1.11, 95 % CI: 1.03-1.20, p = 0.005). The study identified 11 plasma proteins with strong mediating effects, with GDF15 having the strongest association with dementia risk (per 1 SD, HR = 1.24, 95 % CI: 1.16, 1.33, P < 0.001 when LE8z_rev is set at its mean value) and the largest proportion mediated combining PIE and INTMED (62.6 %; 48 % of TE is PIE), followed by adrenomedullin or ADM. A first principal component with 10 top mediators (TNFRSF1A, GDF15, FSTL3, COL6A3, PLAUR, ADM, GFRAL, ACVRL1, TNFRSF6B, TGFA) mediated 53.6 % of the LE8z_rev-dementia effect. Using all the significant PIE (k = 526) proteins, we used OLINK Insight pathway analysis to identify key pathways, which revealed the involvement of the immune system, signal transduction, metabolism, disease, protein metabolism, hemostasis, membrane trafficking, extracellular matrix organization, developmental biology, and gene expression among others. STRING analysis revealed that five top consistent proteomic mediators were represented in two larger clusters reflecting numerous interconnected biological gene ontology pathways, most notably cytokine-mediated signaling pathway for GDF15 cluster (GO:0019221) and regulation of peptidyl-tyrosine phosphorylation for the ADM cluster (GO:0050730). CONCLUSION: Dementia is linked to poor CVH mediated by GDF15 and ADM among several key proteomic markers which collectively explained âˆ¼ 54 % of the total effect.

Infection burden and its association with neurite orientation dispersion and density imaging markers in the UK Biobank.

BACKGROUND: Infection burden (IB), although linked to neurodegeneration, including Alzheimer's Disease (AD), has not been examined against neurite orientation, dispersion, and density imaging (NODDI) measures. METHODS: Among 38,803 UK Biobank adults (Age:40-70 years), we tested associations of total IB (IBtotal, 47.5 %) and hospital-treated IB (IBhosp, 9.7 %) with NODDI measures (5-15 years later), including volume fraction of Gaussian isotropic diffusion (ISOVF), intra-cellular volume fraction (ICVF) and orientation dispersion (OD) indices, using multiple linear regression models. RESULTS: Total and hospital-treated infection burdens (IBtotal and IBhosp) were associated with increased ISOVF, indicating increased free-water component. IBtotal was positively associated with OD, indicating that at higher IBtotal there was greater fanning of neurites. This was more evident in the lower cardiovascular health group. IBhosp was associated with higher OD, and lower ICVF at higher AD polygenic risk. Together, these findings indicate that both total and hospital-treated infections have effects on NODDI outcomes in the direction of poor brain health. These effects were largely homogeneous across cardiovascular health and AD polygenic risk groups, with some effects shown to be stronger at poor cardiovascular health and/or higher AD risk. CONCLUSIONS: Total and hospital-treated infections were associated with poorer white matter microstructure (higher ISOVF or OD or lower ICVF), with some heterogeneity across cardiovascular health and AD risk. Longitudinal studies with multiple repeats on neuroimaging markers in comparable samples are needed.

Posttraumatic stress disorder and insomnia in US military veterans: Prevalence, correlates, and psychiatric and functional burden.

Military veterans have high rates of psychiatric conditions such as posttraumatic stress disorder, which can complicate the clinical management of insomnia. Population-based data are lacking on the prevalence, characteristics and mental health burden of veterans with co-occurring posttraumatic stress disorder and insomnia. The current cross-sectional study analysed data from a nationally representative sample of 4069 US veterans examining the prevalence and comorbidity between posttraumatic stress disorder and insomnia, and their associations with psychiatric and medical comorbidities, suicidality, and psychosocial functioning. Results revealed that 4.0% of US veterans screened positive for posttraumatic stress disorder + insomnia, 7.4% for insomnia only, and 3.2% for posttraumatic stress disorder only. Compared with controls, higher odds of major depressive disorder and generalized anxiety disorder were observed in the posttraumatic stress disorder + insomnia and posttraumatic stress disorder only groups. Moreover, compared with the control group, posttraumatic stress disorder + insomnia and posttraumatic stress disorder only groups had higher odds of current suicidal ideation, while the posttraumatic stress disorder + insomnia group had also higher odds of attempting suicide. Relative to the posttraumatic stress disorder only group, the posttraumatic stress disorder + insomnia group scored substantially lower on measures of cognitive, emotional and social functioning (d = 1.05, 1.04 and 0.87, respectively). This study provides contemporary data regarding current prevalence, correlates, and psychiatric and functional burden of posttraumatic stress disorder + insomnia among US veterans. The results underscore the importance of assessing, monitoring and treating posttraumatic stress disorder and insomnia as part of the efforts to mitigate suicide risk and promote multi-domain functioning in this population.

Serum neurofilament light chain as a prognostic marker of all-cause mortality in a national sample of US adults.

Neurofilament light chain (NfL) is a neuron-specific structural protein released into the extracellular space, including body fluids, upon neuroaxonal damage. Despite evidence of a link in neurological disorders, few studies have examined the association of serum NfL with mortality in population-based studies. Data from the National Health and Nutrition Survey were utilized including 2,071 Non-Hispanic White, Non-Hispanic Black and Hispanic adult participants and adult participants of other ethnic groups (20-85 years) with serum NfL measurements who were followed for ≤ 6 years till 2019. We tested the association of serum NfL with mortality in the overall population and stratified by sex with the addition of potential interactive and mediating effects of cardio-metabolic risk factors and nutritional biomarkers. Elevated serum NfL levels (above median group) were associated with mortality risk compared to the below median NfL group in the overall sample (P = 0.010), with trends observed within each sex group (P < 0.10). When examining Loge NfL as a continuum, one standard deviation of Loge NfL was associated with an increased mortality risk (HR = 1.88, 95% CI 1.60-2.20, P < 0.001) in the reduced model adjusted for age, sex, race, and poverty income ratio; a finding only slightly attenuated with the adjustment of lifestyle and health-related factors. Four-way decomposition indicated that there was, among others, mediated interaction between NfL and HbA1c and a pure inconsistent mediation with 25(OH)D3 in predicting all-cause mortality, in models adjusted for all other covariates. Furthermore, urinary albumin-to-creatinine ratio interacted synergistically with NfL in relation to mortality risk both on the additive and multiplicative scales. These data indicate that elevated serum NfL levels were associated with all-cause mortality in a nationally representative sample of US adults.

Negative aging stereotypes in U.S. military veterans: results from the National Health and Resilience in Veterans Study.

U.S. military veterans are an average 20 years older than non-veterans and have elevated rates of certain health conditions. While negative aging stereotypes have been linked to increased risk for various health conditions, little is known about the prevalence and correlates of these stereotypes in this population. Using data from a nationally representative sample of 4,069 U.S. veterans surveyed between 11/19 and 3/20, we examined (1) the current prevalence of negative aging stereotypes related to physical, mental, and cognitive health and (2) sociodemographic, health, and psychosocial factors associated with these stereotypes. Multivariable regression and relative weight analyses were conducted to identify independent correlates of negative aging stereotypes. Results revealed that 82.3%, 71.1%, and 30.0% of veterans endorsed negative aging stereotypes related to physical, cognitive, and emotional health, respectively. Older age (36.6% relative variance explained), grit (23.6%), and optimism (17.5%) explained the majority of the variance in negative age stereotypes related to physical aging; grit (46.6%), openness to experiences (31.5%), and older age (15.1%) in negative age stereotypes related to cognitive aging; and emotional stability (28.8%), purpose in life (28.8%), and grit (25.3%) in negative age stereotypes related to emotional aging. This study provides an up-to-date characterization of the prevalence and correlates of negative aging stereotypes in U.S. veterans. Results underscore the importance of targeting key correlates of negative aging stereotypes, such as lower grit, as part of efforts to promote health and functioning in this population.

GDF15 and its association with cognitive performance over time in a longitudinal study of middle-aged urban adults.

Serum GDF15 levels are correlated with multiple neurodegenerative diseases. Few studies have tested this marker's association with middle-aged cognitive performance over time, and whether race affects this association is unknown. We examined associations of initial serum GDF15 concentrations with longitudinal cognitive performance, spanning domains of global mental status, visual and verbal memory, attention, fluency, and executive function in a sub-sample of adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 776, Agev1:30-66y, 45.6 % male, 57.0 % African American, 43.0 % below poverty). This analysis consisted of mixed-effects regression models applied to the total selected sample, while also stratifying the analyses by race in the main analyses and further stratifying by sex, age group and poverty status in an exploratory analysis. Our main findings, which passed multiple testing and covariate-adjustment, indicated that GDF15 was associated with poorer baseline performance on several cognitive tests, including animal fluency [overall sample: (Model 1: γ0 ± SE: -0.664 ± 0.208, P < 0.001; Model 2, γ0 ± SE: -0.498 ± 0.217, P < 0.05)]. Among White adults, GDF15 was linked to poorer performance on a brief test of attention (Model 1: γ0 ± SE: -0.426 ± 0.126, P < 0.001; Model 2, γ0 ± SE: -0.281 ± 0.139, P < 0.05); and Trailmaking test, part B (Model 1: γ0 ± SE: +0.129 ± 0.040, P < 0.001; Model 2, γ0 ± SE: +0.089 ± 0.041, P < 0.05), the latter being also linked to higher GDF15 among individuals living below poverty. Among women, GDF15 was associated with poor global mental status (Normalized MMSE: Model 1: γ0 ± SE: -2.617 ± 0.746, P < 0.001; Model 2: γ0 ± SE: -1.729 ± 0.709, P < 0.05). GDF15 was not associated with decline on any of the 11 cognitive test scores considered in âˆ¼ 4 years of follow-up. In sum, we detected cross-sectional associations between GDF15 and cognition, although GDF15 did not predict rate of change in cognitive performance over time among a sample of middle-aged adults. More longitudinal studies are needed to address the clinical utility of this biomarker for early cognitive defects.

Cardiovascular health, infection burden and their interactive association with brain volumetric and white matter integrity outcomes in the UK Biobank.

BACKGROUND: Cardiovascular health is associated with brain magnetic resonance imaging (MRI) markers of pathology and infections may modulate this association. METHODS: Using data from 38,803 adults (aged 40-70 years) and followed-up for 5-15 years, we tested associations of prevalent total (47.5%) and hospital-treated infection burden (9.7%) with brain structural and diffusion-weighted MRI (i.e., sMRI and dMRI, respectively) common in dementia phenome. Poor white matter tissue integrity was operationalized with lower global and tract-specific fractional anisotropy (FA) and higher mean diffusivity (MD). Volumetric sMRI outcomes included total, gray matter (GM), white matter (WM), frontal bilateral GM, white matter hyperintensity (WMH), and selected based on previous associations with dementia. Cardiovascular health was measured with Life's Essential 8 score (LE8) converted to tertiles. Multiple linear regression models were used, adjusting for intracranial volumes (ICV) for subcortical structures, and for demographic, socio-economic, and the Alzheimer's Disease polygenic risk score for all outcomes, among potential confounders. RESULTS: In fully adjusted models, hospital-treated infections were inversely related to GM (ß ± SE: -1042 ± 379, p = 0.006) and directly related to WMH as percent of ICV (Loge transformed) (ß ± SE:+0.026 ± 0.007, p < 0.001). Both total and hospital-treated infections were associated with poor WMI, while the latter was inversely related to FA within the lowest LE8 tertile (ß ± SE:-0.0011 ± 0.0003, p < 0.001, PLE8×IB < 0.05), a pattern detected for GM, Right Frontal GM, left accumbens and left hippocampus volumes. Within the uppermost LE8 tertile, total infection burden was linked to smaller right amygdala while being associated with larger left frontal GM and right putamen volumes, in the overall sample. Within that uppermost tertile of LE8, caudate volumes were also positively associated with hospital-treated infections. CONCLUSIONS: Hospital-treated infections had more consistent deleterious effects on volumetric and white matter integrity brain neuroimaging outcomes compared with total infectious burden, particularly in poorer cardiovascular health groups. Further studies are needed in comparable populations, including longitudinal studies with multiple repeats on neuroimaging markers.

Amygdalobacter indicium gen. nov., sp. nov., and Amygdalobacter nucleatus sp. nov., gen. nov.: novel bacteria from the family Oscillospiraceae isolated from the female genital tract.

Four obligately anaerobic Gram-positive bacteria representing one novel genus and two novel species were isolated from the female genital tract. Both novel species, designated UPII 610-JT and KA00274T, and an additional isolate of each species were characterized utilizing biochemical, genotypic and phylogenetic analyses. All strains were non-motile and non-spore forming, asaccharolytic, non-cellulolytic and indole-negative coccobacilli. Fatty acid methyl ester analysis for UPII 610-JT and KA00274T and additional isolates revealed C16 : 0, C18 : 0, C18:1ω9c and C18:2ω6,9c to be the major fatty acids for both species. UPII 610-JT had a 16S rRNA gene sequence similarity of 99.4 % to an uncultured clone sequence (AY724740) designated as Bacterial Vaginosis Associated Bacterium 2 (BVAB2). KA00274T had a 16S rRNA gene sequence similarity of 96.5 % to UPII 610-JT. Whole genomic DNA mol% G+C content was 42.2 and 39.3 % for UPII 610-JT and KA00274T, respectively. Phylogenetic analyses indicate these isolates represent a novel genus and two novel species within the Oscillospiraceae family. We propose the names Amygdalobacter indicium gen. nov., sp. nov., for UPII 610-JT representing the type strain of this species (=DSM 112989T, =ATCC TSD-274T) and Amygdalobacter nucleatus gen. nov., sp. nov., for KA00274T representing the type strain of this species (=DSM 112988T, =ATCC TSD-275T).

Pathways explaining racial/ethnic disparities in incident all-cause dementia among middle-aged US adults.

INTRODUCTION: Racial disparities in dementia incidence exist, but less is known about their presence and drivers among middle-aged adults. METHODS: We used time-to-event analysis among a sample of 4378 respondents (age 40-59 years at baseline) drawn from the third National Health and Nutrition Examination Surveys (NHANES III) with administrative linkage-spanning the years 1988-2014-to evaluate potential mediating pathways through socioeconomic status (SES), lifestyle, and health-related characteristics. RESULTS: Compared with Non-Hispanic White (NHW) adults, Non-White adults had a higher incidence of AD-specific (hazard ratio [HR] = 2.05, 95% confidence interval [CI]: 1.21, 3.49) and all-cause dementia (HR = 2.01, 95% CI: 1.36, 2.98). Diet, smoking, and physical activity were among characteristics on the pathway between race/ethnicity, SES, and dementia, with health-mediating effects of smoking and physical activity on dementia risk. DISCUSSION: We identified several pathways that may generate racial disparities in incident all-cause dementia among middle-aged adults. No direct effect of race was observed. More studies are needed to corroborate our findings in comparable populations.

Cardiovascular health, infection burden, and incident dementia in the UK Biobank.

INTRODUCTION: Among older adults, total and hospitalized infection may be associated with incidence of all-cause and Alzheimer's disease (AD) dementias, with variation by cardiovascular health (CVH). METHODS: We used Cox proportional hazards (PH) models to examine the relationships between International Classification of Diseases-10th revision (ICD-10)-specific viral and bacterial infectious agents and incident all-cause and AD dementia among 355,046 UK Biobank participants ≥50 years at baseline. Life's Essential 8 (LE8) index reflected CVH. RESULTS: In both sexes, total infection burden (yes vs. no) was associated with all-cause dementia, with significant interactions by LE8 tertiles, whereby this relationship was significant only in the lowest LE8 tertile. Hospital-treated infection burden (yes vs no) was significantly related to all-cause and AD dementia, with no significant interaction with LE8 tertile. Age group patterns were detected. DISCUSSION: AD and all-cause dementia were related to hospital-treated infections, while CVH modified the relationship of total infection burden with all-cause dementia. Highlights Secondary analysis on >355,000 UK Biobank participants ≥50 years at baseline. Alzheimer's disease and all-cause dementia are both related to hospital-treated infection. Cardiovascular health modifies association of infection burden with all-cause dementia.

Circadian variation in stroke onset: Differences between ischemic and hemorrhagic stroke and weekdays versus weekends.

OBJECTIVES: To delineate diurnal variation onset distinguishing ischemic from hemorrhagic stroke, wake from sleep onset, and weekdays from weekends/holidays. MATERIALS AND METHODS: We analyzed patients enrolled in the FAST-MAG trial of field-initiated neuroprotective agent in patients with hyperacute stroke within 2h of symptoms onset. Stroke onset times were analyzed in 1h, 4h, and 12h time blocks throughout the 24h day-night cycle. Patient demographic, clinical features, stroke severity, and prehospital workflow were evaluated for association with onset times. RESULTS: Among 1615 acute cerebrovascular disease patients, final diagnoses were acute cerebral ischemia in 76.5% and Intracerebral hemorrhage in 23.5%. Considering all acute cerebrovascular disease patients, frequency of wake onset times showed a bimodal pattern, with peaks on onsets at 09:00-13:59 and 17:00-18:59 and early morning (00:00-05:59) onset in only 3.8%. Circadian rhythmicity differed among stroke subtypes: in acute cerebral ischemia, a single broad plateau of elevated incidences was seen from 10:00-21:59; in Intracerebral hemorrhage, bimodal peaks occurred at 09:00 and 19:00. The ratio of Intracerebral hemorrhage to acute cerebral ischemia occurrence was highest in early morning, 02:00-06:59. Marked weekday vs weekends pattern variation was noted for acute cerebral ischemia, with a broad plateau between 09:00 and 21:59 on weekdays but a unimodal peak at 14:00-15:59 on weekends. CONCLUSIONS: Wake onset of acute cerebrovascular disease showed a marked circadian variation, with distinctive patterns of a broad elevated plateau among acute cerebral ischemia patients; a bimodal peak among intracerebral hemorrhage patients; and a weekend change in acute cerebral ischemia pattern to a unimodal peak.

A case of natural infection with Dirofilaria immitis in a coati (Nasua narica) from Mexico.

This paper aims to describe the natural infection with Dirofilaria immitis in Nasua narica (white-nosed coati) from Yucatán, Mexico. Two carcasses of N. narica were collected on a highway that crosses through a dense forest with patches used for agriculture and livestock activities. We performed necropsies, and two female adult nematode parasites from the heart of one specimen were collected and preserved for their molecular identification using a conventional PCR directed at a fragment of the small subunit (18S) ribosomal RNA (18S-rRNA) gene. Bioinformatic analysis showed a similarity of 99 % with three sequences from D. immitis (two from Japan). Additionally, we performed a phylogenetic tree with the recovered sequence. All these analyses showed that D. immitis is present in N. narica from Mexico. The transmission of D. immitis toward populations of Nasua sp. may be due to indirect and accidental contact with domestic dogs or wild canids that share the same environment.

Disaster waste management challenges and enabling factors for strategic planning: The case of the Beirut Port explosion.

Disasters occur in both developed and developing countries, generating large amounts of disaster waste including construction and demolition (C&D) waste that needs to be appropriately managed. While developed countries are capable of implementing adequate disaster waste management (DWM) strategies to facilitate their recovery processes, developing countries generally struggle to find the resources and expertise needed to develop such strategies. Lebanon is a developing country vexed by several systemic challenges that hindered its abilities to manage disaster waste. In this paper, we focus on the Beirut Port explosion (4 August 2020), which generated more than 800,000 tonnes of disaster wastes. This study first assesses the executed strategies and identifies their enabling factors and implementation challenges. It then proposes a framework for the proper management of disaster waste, which was validated through 18 in-depth interviews with experts and stakeholders involved in disaster management. Interview notes and transcripts were analyzed using an inductive-deductive process that allowed to identify themes using the constant comparative method. The data revealed that the main barriers toward implementing a successful DWM strategy were the absence of appropriate technologies, infrastructure, expertise, legislative framework and financial resources. The study concludes by proposing a DWM roadmap that includes contingency, risk reduction and implementation plans (IPs) that can enhance decision-making and ease the recovery process.

Comparative Single-Dose mRNA and ChAdOx1 Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2, Including Variants of Concern: Test-Negative Design, British Columbia, Canada.

BACKGROUND: In British Columbia, Canada, most adults 50-69 years old became eligible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in April 2021, with chimpanzee adenoviral vectored vaccine (ChAdOx1) restricted to ≥55-year-olds and second doses deferred ≥6 weeks to optimize single-dose coverage. METHODS: Among adults 50-69 years old, single-dose messenger RNA (mRNA) and ChAdOx1 vaccine effectiveness (VE) against SARS-CoV-2 infection and hospitalization, including variant-specific, was assessed by test-negative design between 4 April and 2 October 2021. RESULTS: Single-dose VE included 11 861 cases and 99 544 controls. Median of postvaccination follow-up was 32 days (interquartile range, 15-52 days). Alpha, Gamma, and Delta variants comprised 23%, 18%, and 56%, respectively, of genetically characterized viruses. At 21-55 days postvaccination, single-dose mRNA and ChAdOx1 VE (95% confidence interval [CI]) was 74% (71%-76%) and 59% (53%-65%) against any infection and 86% (80%-90%) and 94% (85%-97%) against hospitalization, respectively. VE (95% CI) was similar against Alpha and Gamma infections for mRNA (80% [76%-84%] and 80% [75%-84%], respectively) and ChAdOx1 (69% [60%-76%] and 66% [56%-73%], respectively). mRNA VE was lower at 63% (95% CI, 56%-69%) against Delta but 85% (95% CI, 71%-92%) against Delta-associated hospitalization (nonestimable for ChAdOx1). CONCLUSIONS: A single mRNA or ChAdOx1 vaccine dose gave important protection against SARS-CoV-2, including early variants of concern. ChAdOx1 VE was lower against infection, but 1 dose of either vaccine reduced the hospitalization risk by >85% to at least 8 weeks postvaccination. Findings inform program options, including longer dosing intervals.

The role of MicroRNA as a potential diagnostic and prognostic biomarker for cerebral aneurysms.

OBJECTIVES: To identify the dysregulated functional miRNAs, miRNA-16, miRNA-143, and miRNA-200 as potential biomarkers of cerebral aneurysms(CAs) to aid in diagnosis and prognosis. METHODS: This is a prospective case-control study conducted among patients with CA. All patients' computed tomography angiography (CTA) and interventional angiogram were assessed and studied. The miRNAs were isolated and quantified from peripheral blood samples and the expression profiling was done using TaqMan chemistry on Real-Time PCR. RESULTS: A total of 37 samples were included. Three cases had double aneurysms and 10 cases presented with aneurysmal rupture. miRNA-16, miRNA-143, and miRNA-200 were upregulated with an absolute fold-change of >8 in the CA group in comparison to controls (p<0.05). miRNA-200 showed double expression in patients with single aneurysm. A statically significant increase was observed in the expression of miRNA-143 in patients who had an aneurysmal rupture with p<0.05. Diabetic patients showed an obvious increase in miRNA-200 (13.03 folds) and miRNA-16 (26.82 folds) expression. Also, there was a notable elevation in miRNA-16, miRNA-143, and miRNA-200 in patients who had hypertension in comparison to those who did not. CONCLUSION: miRNA-16, miRNA-143, and miRNA-200 showed statically significant higher expression among cases with cerebral aneurysms in comparison to controls. Thus, these preliminary results of miRNAs biomarkers are promising future tool to be used for aneurysmal screening.

Prevalence and Predictors of Food Insecurity Among Stroke Survivors in the United States.

BACKGROUND: Food insecurity (FI)-lack of consistent access to food due to poor financial resources-limits the ability to eat a healthy diet, which is essential for secondary stroke prevention. Yet, little is known about FI in stroke survivors. METHODS: Using data from the US National Health and Nutrition Examination Survey from 1999 to 2015, we analyzed the prevalence, predictors, and temporal trends in FI among adults with and without self-reported prior stroke in this cross-sectional study. Age-standardized prevalence estimates were computed by self-reported history of stroke over survey waves. Multivariable logistic regression models were performed for the National Health and Nutrition Examination Survey participants who had a prior stroke to identify independent predictors of FI by self-reported history of stroke. RESULTS: Among 48 242 adults ≥20 years of age, 1877 self-reported history of stroke. FI was more prevalent among people with prior stroke (17%) versus those without prior stroke (12%; P<0.001). Prevalence of FI increased over time from 7.8% in 1999 to 42.1% in 2015 among stroke survivors and from 8% to 17% among individuals without prior stroke (P<0.001). The age-standardized prevalence of FI over the entire time was 24% among stroke survivors versus 11% among individuals without prior stroke (P<0.001). In the adjusted model, younger age (adjusted odds ratio [aOR], 0.96 [0.95-0.97]; P<0.01), Hispanic ethnicity (aOR, 2.12 [1.36-3.31]; P<0.01), lower education (aOR, 1.67 [1.17-2.38]; P<0.01), nonmarried status (aOR, 1.49 [1.01-2.19]; P=0.04), and poverty income ratio <130% (aOR, 3.78 [2.55-5.59]; P<0.01) were associated with FI in those with prior stroke. CONCLUSIONS: One in 3 stroke survivors reported FI in 2015, nearly double the prevalence in those without stroke. Addressing the fundamental drivers of FI and targeting vulnerable demographic groups may have a profound influence on stroke prevalence.

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study).

BACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .

Ischemia reperfusion injury facilitates lung allograft acceptance through IL-33-mediated activation of donor-derived IL-5 producing group 2 innate lymphoid cells.

Pathways regulating lung alloimmune responses differ from most other solid organs and remain poorly explored. Based on our recent work identifying the unique role of eosinophils in downregulating lung alloimmunity, we sought to define pathways contributing to eosinophil migration and homeostasis. Using a murine lung transplant model, we have uncovered that immunosuppression increases eosinophil infiltration into the allograft in an IL-5-dependent manner. IL-5 production depends on immunosuppression-mediated preservation of donor-derived group 2 innate lymphoid cells (ILC2). We further describe that ischemia reperfusion injury upregulates the expression of IL-33, which functions as the dominant and nonredundant mediator of IL-5 production by graft-resident ILC2. Our work thus identifies unique cellular mechanisms that contribute to lung allograft acceptance. Notably, ischemia reperfusion injury, widely considered to be solely deleterious to allograft survival, can also downregulate alloimmune responses by initiating unique pathways that promote IL-33/IL-5/eosinophil-mediated tolerance.

Plasma neurofilament light and its association with all-cause mortality risk among urban middle-aged men and women.

BACKGROUND: Neurofilament light chain (NfL) is released into the blood during neuronal damage. NfL is linked to mortality in neurological disorders, remaining unexplored in population studies. We investigated whether initial (v1) and annualized change (δ) in plasma NfL can predict all-cause mortality in middle-aged dementia-free urban adults. METHODS: Longitudinal data were from 694 participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span study (HANDLS, mean agev1: 47.8 years, 42% male, 55.8% African American). Plasma NfL was measured prospectively at three visits. Analyses included Cox proportional hazards models for all-cause mortality risk and 4-way decomposition testing for interaction and mediation. RESULTS: Unlike men, women exhibited a direct association between δNfL (above vs. below median) and all-cause mortality risk in both the minimally (HR = 3.91, 95% CI 1.10-13.9, p = 0.036) and fully adjusted models (HR = 4.92, 95% CI 1.26-19.2, p = 0.022), and for δNfL (per unit increase) in the full model (HR = 1.65, 95% CI 1.04-2.61, p = 0.034). In both models, and among women, 1 standard deviation of NfLv1 was associated with an increased all-cause mortality risk (reduced model: HR = 2.01, 95% CI 1.24-3.25, p = 0.005; full model: HR = 1.75, 95% CI 1.02-2.98, p = 0.041). Only few interactions were detected for cardio-metabolic risk factors. Notably, NfLv1 was shown to be a better prognostic indicator at normal hsCRP values among women, while HbA1c and δNfL interacted synergistically to determine mortality risk, overall. CONCLUSIONS: These findings indicate that plasma NfL levels at baseline and over time can predict all-cause mortality in women and interacts with hsCRP and HbA1c to predict that risk.