Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and brain white matter microstructural integrity: the UK Biobank study.

The plasma proteome can mediate associations between periodontal disease (Pd) and brain white matter integrity (WMI). We screened 5089 UK Biobank participants aged 40-70 years for poor oral health problems (POHP). We examined the association between POHP and WMI (fractional anisotropy (FA), mean diffusivity (MD), Intracellular Volume Fraction (ICVF), Isotropic Volume Fraction (ISOVF) and Orientation Diffusion (OD)), decomposing the total effect through the plasma proteome of 1463 proteins into pure mediation, pure interaction, neither, while adjusting for socio-demographic and cardiovascular health factors. Similarly, structural equations modeling (SEM) was conducted. POHP was more prevalent among men (12.3% vs. 9.6%), and was associated with lower WMI on most metrics, in a sex-specific manner. Of 15 proteins strongly associated with POHP, growth differentiation factor 15 (GDF15) and WAP four-disulfide core domain 2 (WFDC2; also known as human epididymis protein 4; HE4) were consistent mediators. Both proteins mediated 7-8% of total POHP effect on FAmean. SEM yielded significant total effects for FAmean, MDmean and ISOVFmean in full models, with %mediated by common latent factor (GDF15 and WFDC2) ranging between 13% (FAmean) and 19% (ISOVFmean). For FA, mediation by this common factor was found for 16 of 49 tract-specific and global mean metrics. Protein metabolism, immune system, and signal transduction were the most common pathways for mediational effects. POHP was associated with poorer WMI, which was partially mediated by GDF15 and WFDC2.

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.

Associations between AHA's Life's Essential 8 and cognition in midlife and older adults.

INTRODUCTION: This study evaluated the associations between Life's Essential 8 (LE8) and cognitive performance, and compared the strength of the relationships of Life's Simple 7 (LS7) and LE8 to cognition in midlife and older adults. METHODS: Participants (N = 1539) were from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Cross-sectional multivariable regression examined the associations between LE8 and cognition. Secondary analyses compared model performance between LE8 and LS7 measures on cognition from the same available sample. RESULTS: Higher LE8 scores were associated with better global cognitive performance, working memory, and attention. The LS7 model outperformed the LE8 model on global cognitive performance, but the LE8 model outperformed the LS7 model for the working memory domain. DISCUSSION: Better cardiovascular health (CVH) was associated with better cognitive performance among US middle-aged and older adults. However, the association between CVH and specific cognitive domains varies when using LE8 versus LS7. HIGHLIGHTS: Cardiovascular health (CVH) is associated with cognitive performance. Life's Essential 8 (LE8) is a new construct to quantify CVH. Associations between LE8 and cognition were assessed. Higher LE8 was associated with better global cognitive performance. Higher LE8 was also associated with better working memory and attention.

Infection burden, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer's disease dementia in a large national survey.

INTRODUCTION: Relationships and interplay of an infection burden (IB) and periodontal pathogens or periodontal disease (Pd) markers with Alzheimer's disease (AD) and all-cause dementia among US adults were examined. METHODS: Less than or equal to 2997 participants from the National Health and Nutrition Survey III were linked to CMS-Medicare [≥45 years (1988-1994); ≤30 years follow-up]. RESULTS: Hepatitis C (hazard ratio = 3.33, p = 0.004) and herpes simplex virus 2 were strongly associated with greater all-cause dementia risk. Porphyromonas gingivalis and Streptococcus oralis were associated with greater AD risk at higher IB. The red-green periodontal pathogen cluster coupled with higher IB count increased the risk of all-cause dementia among minority racial groups. Pocket probing depth associated with dementia risk at lower IB in the overall sample. DISCUSSION: Select viruses and bacteria were associated with all-cause and AD dementia, while the IB interacted with Pd markers in relation to these outcomes. HIGHLIGHTS: Interplay of infection burden (IB) and periodontal disease with dementia was tested. ≤2997 participants from NHANES III were linked to Medicare. Hepatitis C and herpes simplex virus 2 strongly associated with dementia risk. Tetanus sero-positivity increased Alzheimer's disease (AD) risk. Porphyromonas gingivalis and Streptococcus oralis associated with AD at higher IB. Red-green periodontal cluster at high IB, increased dementia in racial minorities. Pocket probing depth associated with dementia risk at lower IB.

Father-separation and well-being in forcibly displaced Syrian children.

Forcibly displaced children often face separation from their parents, particularly fathers. These children endure the hardships of war, displacement, and the loss of a key attachment figure. Despite the critical role of attachment in children's well-being during periods of heightened stress, the impact of separation due to war and displacement has received little attention in empirical work. Findings from 1544 Syrian refugee children (Mage = 10.97, SD = 2.27) living in informal settlements in Lebanon with their mothers (Mage = 38.07, SD = 8.49), including 367 father-separated children, show that father-separated children experienced more war-related events and worse refugee environments. Structural equation modelling showed that beyond the direct relation of war exposure and quality of the refugee environment on well-being, father separation was uniquely related to more depressive symptoms and worse self-development, but not to anxiety, PTSD, or externalising problems in children. Maternal parenting did not explain these outcomes, though it had a protective function for children's well-being.

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.