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Background: The NINDS criteria define Traumatic Encephalopathy Syndrome (TES) as the clinical manifestation of the neuropathologically diagnosed chronic traumatic encephalopathy (CTE). The core clinical features of TES include both cognitive and neuropsychiatric symptoms, the latter termed neurobehavioral dysregulation (NBD). We explored potential biological correlates of NBD by investigating fluid biomarkers of neuronal damage, astrogliosis, phosphorylated tau (pTau), neuroinflammation, and catecholamines in former American football players. Method: Our cohort consisted of former professional (PRO) and college (COL) American football players from the DIAGNOSE CTE Research Project. NBD was measured by four subscales (i.e., explosivity, emotional dyscontrol, impulsivity, affective lability) and a total NBD score, derived by factor analysis of multiple self‐report neuropsychiatric measures. Plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), CSF total tau and pTau181/231/217, as well as CSF biomarkers related to neuroinflammation (IL‐6, CRP, TNF‐α, VEGF‐A), were measured with various well‐validated immunoassay methods. Catecholamines in CSF (dopamine, 3,4‐dihydroxyphenylacetic acid, 3,4‐dihydroxyphenylalanine, noradrenaline, 3,4‐dihydroxyphenylglycol) were measured with HPLC. Multivariate linear regression models assessed the relationships between biomarkers and NBD scales, adjusted for age, BMI, race, and APOE e4, including stratification by exposure group, i.e., PRO, COL. Result: Demographics and biomarker levels are displayed in Table 1. High levels of IL‐6 were significantly associated with higher scores of all NBD subscales, independent of exposure group. Other significant relationships included plasma NfL with emotional dyscontrol and impulsivity. Within the college group, CSF pTau181 was significantly associated with emotional dyscontrol and CSF noradrenaline with explosivity, emotional dyscontrol, impulsivity, and total NBD score. (Table 2 & Figure 1). IL‐6 models were repeated with measures of cognitive dysfunction (another core feature of TES) added as covariates; these analyses again found significant relationships between IL‐6 and NBD, irrespective of cognitive functioning. Conclusion: We observed specific fluid biomarkers related to NBD in former American football players. Of note were the associations between IL‐6 and all NBD subscales (and not with cognitive functioning), suggesting that neuroinflammation may be a specific component in the expression of NBD symptoms. Future studies will investigate how these neuroinflammatory processes are related to other biomarkers, level of RHI exposure, and neuropathology. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) has been reported to increase risk of Alzheimer's dementia (AD). It remains unknown whether mild TBI (mTBI) caused by blast in Veterans confers a similar increase of risk. This study investigated early AD changes defined by cerebrospinal fluid (CSF) AD biomarkers in Veterans with blast mTBI. Method: Fifty‐one Veterans with mTBI, 34 non‐mTBI Veterans, and 51 non‐mTBI civilians were recruited from Seattle, Washington. Age‐matched Veteran and civilian non‐mTBI participants had no lifetime history of TBI. All blast‐mTBI Veterans had experienced at least one war zone blast or combined blast/impact exposure, with acute symptoms meeting VA/Department of Defense criteria for mTBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of CSF. CSF biomarkers were measured at the Clinical Neurochemistry Lab in Mölndal, Sweden, using Meso Scale Discovery (MSD) assays for Aβ40 and Aβ42, and Innotest ELISAs for phosphorylated Tau181 (pTau181) and total Tau (tTau). Result: Differences in all 4 CSF AD biomarkers between participants with and without mTBI were highly age‐dependent and most pronounced in older ages (Figure 1). Both CSF Aβ40 and Aβ42 became lower as age increasing in the mTBI group starting around age 40‐45 years, while they increased with age in the non‐mTBI participants. In contrast, CSF tTau and pTau181 mean levels remained relatively constant with age in participants with mTBI, but increased after age 45 in the non‐mTBI participants. Consequently, for participants aged 50+ years, Veterans with mTBI had lower mean AD biomarkers than the non‐mTBI participants. Similarly, the differences in cognitive performance were age‐dependent, i.e., poorer performance in older Veterans with mTBI than in the non‐mTBI participants. Furthermore, the relationships between CSF Aβ42 and cognitive performance were also age‐dependent; specifically, in participants aged 45+ years, lower CSF Aβ42 level was associated with poorer performance on tests of verbal fluency and memory. Conclusion: The earliest AD biomarker, CSF Aβ42, started to decrease in middle‐aged Veterans with mTBI, more than a decade earlier than those without mTBI in our earlier study, suggesting mTBI may accelerate brain deposition of Aβ and increase risk for AD. [ABSTRACT FROM AUTHOR]

Background: During sleep, the glymphatic system facilitates rapid exchange of fluid through brain tissues, clearing solutes, including amyloid β (Aβ), tau, and α synuclein that accumulate through the course of waking activity. Glymphatic clearance is widely believed to underlie the restorative effects of sleep on cognition, and its impairment is proposed to reflect the biological basis for the corrosive effects of sleep disruption. We sought to determine if glymphatic function or sleep EEG predicted changes in cognitive performance and overnight differences in Aβ biomarker levels using a new non‐invasive investigational medical device (IMD) to measure glymphatic function by dynamic impedance spectro‐tomography. Method: Eighteen healthy 50‐65 y/o participants were enrolled in a cross‐over randomized control clinical trial encompassing one night of sleep and one night of sleep deprivation. Participants were instrumented with the IMD and overnight change in brain parenchymal resistance to flow, R, was measured. Sleep EEG powerbands, slow (0.4‐1Hz), delta (1‐4Hz), beta (15‐30Hz), and time spent in N2, N3 and REM sleep were derived from the device EEG. In both sleep and sleep deprivation interventions, cognitive tests (symbol digit modality test, SDMT; psychomotor vigilance test, PVT) were administered at 7am and blood Aβ biomarkers (Aβ40; Aβ42) were taken at 10pm and 7am. Result: Overnight parenchymal resistance R predicted intraindividual paired differences (sleep – sleep deprivation) in cognitive test scores (A SDMT ρ = ‐0.65, p = 0.003; B PVT STD RT, ρ = 0.41, p = 0.095) and Aβ42 blood amyloid biomarker changes (C Aβ42 ρ = ‐0.53, p = 0.03; D Aβ40 ρ = ‐0.33, p = 0.21). Sleep EEG powerbands and time spent in N2, N3, and REM sleep were not predictive of sleep‐related changes in cognition or plasma Aβ biomarker levels. Conclusion: Glymphatic function, measured continuously by dynamic impedance spectro‐tomography, predicted changes in the restorative effect of sleep on cognition and plasma Ab biomarker levels as hypothesized, but not previously demonstrated. In contrast, sleep EEG powerbands and time spent in N2, N3 and REM were not predictive. Detection of glymphatic impairment in real‐world settings may permit (i) early identification of individuals at‐risk for developing sleep‐related Alzheimer's disease pathology, and (ii) enable precision targeted enhancement of glymphatic function to enhance glymphatic function and pathological protein clearance. [ABSTRACT FROM AUTHOR]

Background: Perivascular glymphatic exchange contributes to the clearance of amyloid β, tau, and α synuclein primarily during sleep. Glymphatic function has been assessed in human populations solely through neuroimaging, including contrast‐enhanced magnetic resonance imaging (CE‐MRI). Using a newly developed investigational medical device (IMD) to measure brain parenchymal resistance to fluid flow by dynamic impedance spectro‐tomography, we evaluated the performance of this putative measure of glymphatic function against "gold‐standard" CE‐MRI. Method: Healthy 55‐65 y/o participants were enrolled in a cross‐over randomized control clinical trial encompassing one night of sleep/sleep deprivation followed by 4hr morning window of wake/sleep. Intravenous CE‐MRI was obtained prior to (T0) and following (T1) the 4hr window. Participants were instrumented with the IMD to measure continuous changes in brain parenchymal resistance (R). For the ROIs of interest, contrast enhancement (CE) was measured as the ratio of the T1/T0 MRI signal. The ratio CEp/CEd of anatomically proximal ROIs (CEp) to distal ROIs (CEd) was used to measure increasing (CEp/CEd ≤ 1) or decreasing (CEp/CEd > 1) net contrast movement. The predictive value of the R measured by the IMD, multiple EEG powerbands, and time spent in N2, N3 and REM sleep were tested against the CE‐MRI ROI ratios. Data from fourteen intervention periods were available for analysis. Result: IMD parenchymal resistance R predicted IV CE‐MRI contrast movement through blood, cerebrospinal fluid, and interstitial brain compartments (Table 1, Figure 1). EEG slow power predicted contrast movement into more proximal ROIs only. Other powerbands and hypnogram sleep stages were not predictive of contrast movement. Conclusion: EEG powerbands (increased slow, reduced beta) were weakly associated with increased glymphatic exchange measured by CE‐MRI. Parenchymal resistance R measured by the IMD were robust predictors of contrast movement from proximal (ventricles, subarachnoid) CSF compartments, through parenchymal compartments (gray matter, white matter). These findings begin to validate IMD‐derived parenchymal R as non‐imaging measure of glymphatic function. Detection of glymphatic impairment in real‐world settings may permit (i) early identification of individuals at‐risk for developing sleep‐related Alzheimer's disease pathology, and (ii) enable precision targeted enhancement of glymphatic function to enhance glymphatic function and pathological protein clearance. [ABSTRACT FROM AUTHOR]

Background: Glymphatic exchange of interstitial solutes may underlie the observed clinical association between sleep, aging, and Alzheimer's Disease (AD). Furthermore, glymphatic function is currently primarily measured by contrast‐based (CE) MRI, limiting its clinical utility. In this work we test a wearable device to assess sleep architecture and a diffusion‐based intravoxel incoherent motion (IVIM) protocol to detect sleep‐related changes in the glymphatic system at two sites. Method: Site 1: We recruited 13 participants (age = 62±3 yrs. old, 4F) and assessed them prior to and following overnight sleep and sleep deprivation. Sleep efficiency, relative slow delta power, N2, N3, and REM durations were measured with the wearable device. Using CE‐MRI, delayed contrast enhancement in the subarachnoid (SASe) was measured at ∼4 hrs after contrast injection to assess brain parenchymal solute clearance during a second recovery sleep opportunity. For contrast‐free MRI, we measured slow subarachnoid CSF flow (D*) in the SAS using IVIM at night and in the morning. Cognitive assessments were conducted in the morning only. Site 2: We conducted an identical sleep/sleep deprivation study (N = 10, age = 54±5 yrs. old, 9F), but without CE MRI. We tested the correlation between SASe and D*. Next, we compared changes in D* between a night of sleep and sleep deprivation and tested associations with sleep parameters. Result: A. Change in D* after sleep or awake opportunity was significantly associated with SASe (p = 0.05) Greater SAS D* was associated with lesser contrast in the SAS. B. Although not significant, D* reproducibly decreases with sleep deprivation and remains unchanged after sleep. C‐D. Differences in D* during sleep were significantly associated with slow wave spindle number (p = 0.03) and N3 duration (p = 0.04). E. D* measurement concurrent with PVT administrations showed that while greater D* after staying awake was associated with longer reaction times, greater D* after a night of sleep was associated with shorter reaction times. Conclusion: With a wearable device, remote sleep assessment was successfully performed. IVIM‐derived D* was associated with CE MRI measures in the SAS providing a non‐invasive alternative to study brain fluid transport. D* showed associations with sleep parameters as well as sleep‐associated cognition. [ABSTRACT FROM AUTHOR]

Background: The novel diffusion‐based Neurite Orientation and Dispersion Imaging (NODDI) model may provide complementary information to Diffusion Tensor Imaging (DTI) to increase sensitivity in characterizing tissue microarchitecture. We examined if one or a combination of both approaches can improve our understanding of at‐risk tissue in and around white matter hyperintensities (WMH). Method: From ADNI3, we identified individuals [n = 54, age = 78 ± 7, 46% F) with concurrent measures of multi‐shell DTI, 3D FLAIR, and 3D MPRAGE. We segmented WMH from structural data using Lesion Segmentation Toolbox. We derived DTI (FA, MD) and NODDI parameters (NDI, ODI, Fiso) using QSIprep. We dilated up to 5 mm outside the WMH, applied an FA threshold of ≥ 0.2 to exclude gray matter, calculated DTI and NODDI parameters at 1 mm intervals within this region. We performed Pearson correlations between all parameters. Assuming normal white matter at 5 mm, we normalized these parameters with their respective values at 5 mm and plotted the spatial variation of each parameter in and outside the WMH. Result: Normalized DTI and NODDI parameters representing spatial variations within the 5 mm region are shown in Fig 1A. Table 1 shows p‐values comparing DTI and NODDI parameters between WMH the subsequent regions outside it. Compared to WMH, Fiso was significantly different at all distances. FA showed similar spatial characteristics with NDI and was negatively correlated with ODI. Fiso correlated very strongly with MD. Conclusion: In the WMHs and its immediate vicinity, low FA, NDI, ODI suggest lower cell density, while low Fiso and MD suggest low extracellular fluid volume. Together these observations may reflect cytotoxic edema, cell loss, and injury. Normal appearing white matter (3‐5 mm) showed high FA, NDI, ODI, and low MD consistent with high cell density and normal extracellular water. In the transition between WMH vicinity and normal white matter, low FA, NDI, ODI, high MD and Fiso suggest cell loss only. This transition region could be at risk of converting to WMH. Future work will include longitudinal evaluation of WMH growth in the at‐risk tissue. However, final validation of WMH pathology will need histological confirmation. [ABSTRACT FROM AUTHOR]

Background: The Hachinski ischemic score (HIS) scale is used to exclude as much as possible, individuals with dominant cerebrovascular pathology from those with dominant AD pathology. White matter hyperintensities (WMH) are the gold‐standard for evaluating cerebrovascular pathology and linked to worsening cognitive impairment. HIS ≤ 4 are used to minimize non‐AD pathology in ADNI participants. Here we sought to understand whether HIS scores for hypertension (HMHYPERT) in ADNI3 were associated with greater WMH burden (and hence cerebrovascular pathology) even within individuals with HIS ≤ 4. Method: We compared HMHYPERT scores between individuals with normal cognition (CN) and with mild cognitive impairment (MCI), and participants and correlated with percent WMH burden. A total of 263 subjects screened for ADNI3 (92 MCI [38 F], age = 73 ± 6; 146 CN [94 F], age = 74 ± 7) who had HIS scores and FLAIR MRI acquisitions within a year of each other. 25 All AD participants were excluded. WMH burden was calculated by segmenting them using the Lesion Segmentation Toolbox and normalizing their volume by total intracranial volume. We used the HMHYPERT as a vascular risk factor, excluding those with any focal neurological symptoms. For analysis, we dichotomized participants into those with HMHYPERT = 0 and HMHYPERT>0. To examine whether a non‐zero HMHYPERT score corresponds to greater WMH burden, we examined the prevalence of WMH in between these 2 groups and within the MCI and CN groups. Result: Although not significant, HMHYPERT scores were higher in MCI. (Fig. 1A, MCI = 0.48±0.50, CN = 0.39±0.49). We found a greater proportion of MCI subjects had HMHYPERT>0 than CN subjects (Fig. 1B, HMHYPERT = 0: CN = 61.0% and MCI = 52.2%; HMHYPERT > 0: CN = 40.0% and MCI = 48.1%). WMH burden was greater in MCI (0.33±0.53) than CN (0.20±0.32) (Fig. 2A). MCI participants with HMHYPERT>0 had the highest WMH burden followed by MCI participants with HMHYPERT = 0, CN with HMHYPERT >0, and CN with HMHYPERT = 0 had the lowest WMH burden. (Fig. 2B). Conclusion: Cerebrovascular pathology increases significantly with diagnosis, but its severity increases further with findings of hypertension even when total HIS ≤ 4. [ABSTRACT FROM AUTHOR]

Background: The Hachinski Ischemia Scale (HIS) differentiates AD and vascular dementia and is used to include individuals with minimal vascular risk factors in ADNI i.e., HIS ≤ 4. HIS score includes history of hypertension (HMHYPERT), a known risk for mild cognitive impairment (MCI) and vascular dementia. Cerebrovascular disease affects performance on tasks involving executive function, such as, planning and processing speed more than memory. Here, we determined if HMHYPERT scores influences executive functioning in all ADNI3 participants with normal cognition (CN) and MCI even with minimal vascular risks. Method: We included a total of 272 participants (102 MCI, age = 74± 8 [42F, 50 HMHYPERT>0], MoCA = 23 ±3 and 170 CN, age = 73 ±6, [109F, 62 HMHYPERT>0], MoCA = 26 ±3), who underwent HIS, Trails Making Test B, Clock Drawing and Copy scores for executive function, and The Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory Test (LOGMEM) scores for memory performance within 12 months. We converted both memory tests into z‐scores and created a composite memory score. Similarly, we created a composite executive function score. To determine if HMHYPERT was associated particularly with executive function, we ran the linear regression analyses twice for the two composite cognitive scores. The following model was used: Composite score ∼ Normalized Age + Sex + Cognitive status * HMHYPERT. Result: Executive function: Fig. 1 A shows scores for Trails B, Clock Draw and Clock Copy. The regression analysis showed that executive function was associated with only sex and HYMHYPERT (p<0.05). Memory function: Fig. 1 B shows scores for Logical Memory and RAVLT tests in CN and MCI. As expected, MCI groups demonstrate the lowest averages compared to CN groups. As expected, regression analysis showed that memory performance was strongly determined by diagnostic status (p<0.001). Age was significantly associated with memory performance (p<0.05). HMHYPERT was only marginally significantly associated with memory performance (p = 0.08). Conclusion: Using HMHYPERT score as a measure of vascular risk, we observed notable differences in executive function. Although HIS scores ≤ 4 minimize vascular pathology in ADNI3, cognitive performance is still associated with these scores. [ABSTRACT FROM AUTHOR]

Background: Although emerging data suggest a direct link between sleep duration, aging, and cognitive performance, the impact of longitudinal sleep patterns have on Alzheimer's disease‐associated pathology and cognitive decline remains unclear. Method: Utilizing longitudinal data on self‐reported sleep duration collected within the Seattle Longitudinal Study, we used a Cox proportional hazard (CPH) regression to evaluate the relationship between longitudinal sleep factors on the development of cognitive decline. Additional analysis in a sub‐cohort utilized multivariate linear regression prediction analyses to evaluate the predictive value of these longitudinal sleep factors on the incidence of developing cognitive impairment over an interval of 10 years. A cohort within the study received MRI and FLAIR neuroimaging, enabling the assessment of the impact these longitudinal sleep factors have on subcortical white matter MRI‐visible perivascular space burden (PVS). A semi‐automated segmentation algorithm accounted for PVS total burden and volume, as well as average PVS width, length, and median volume across participants, blinded by group. Result: CPH analysis found years of education (HR 1.12, 95% CI 1.02, 1.22), APOE4 status (HR 2.18, 95% CI 1.37, 3.49), higher depression scores (HR 1.08, 95% CI 1.04, 1.13), short sleep phenotype (HR 1.78, 95% CI 1.03, 3.08) and increased sleep variability (HR 3.10, 95% CI 1.66, 5.80) were significantly associated with cognitive impairment. Further, when including these factors into our linear regression prediction analyses, age (p<0.0001), depression (p = 0.01) and sleep variability (p = 0.042) were significant predictors of cognitive impairment over a 10‐year period. Preliminary analysis showed significant association between high sleep variability and increased whole‐brain PVS volume (p = 0.04) and length (p = 0.03), with a significant correlation between sleep variability and median PVS volume (p = 0.04). Follow‐up analysis evaluated PVS features within the wider cohort. Conclusion: These findings suggest that variability in longitudinal self‐reported sleep duration exerts a previously unappreciated influence on downstream cognitive performance and pathological processes, potentially including glymphatic dysfunction. These findings elaborate the link between sleep instability, aging, cognitive decline and neuropathologic disease state. Future studies should evaluate these findings on an independent cohort to assess whether sleep variability of different time scales (weeks, years, decades) exerts similar effects on these outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy. Methods We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth. Results At one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P < 0.001) times more likely to be anemic compared to HIV-negative infants. Among, HIV-negative infants, EPO was or tended to be inversely associated with hemoglobin and was significantly positively associated with TfR throughout the first 6 months of life; TfR was significantly inversely associated with ferritin at 6 months; and EPO explained more of the variability in TfR than did ferritin. Among infected infants, the inverse association of EPO to hemoglobin was attenuated during early infancy, but significant at 6 months. Similar to HIV-negative infants, EPO was significantly positively associated with TfR throughout the first 6 months of life. However, the inverse association between TfR and ferritin observed among HIV-negative infants at 6 months was not observed among infected infants. Between birth and 6 months, mean serum ferritin concentration declined sharply (by ~90%) in all three groups of babies, but was significantly higher among HIV-positive compared to HIV-negative babies at all time points. Conclusion HIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months.

An unprecedented irruption of thousands of Razorbills Alca torda into Florida in winter 2012/13 was followed by a "wreck" of Razorbills and Atlantic Puffins Fratercula arctica in outer Cape Cod, Massachusetts, in January-March 2013. We describe these events using citizen-science sources (eBird and beached-bird surveys) and band recoveries, then we discuss them in relation to extreme weather and oceanographic change. We explored effects on likely source populations using census and monitoring data, along with possible contributions from population increases, reduced food supply, and extreme weather. Winter 2012/13 followed a marine heatwave throughout the northwest Atlantic, whose effects included reduced availability of plankton. We attribute the irruption of Razorbills into Florida partly to delayed effects of Hurricane Sandy, which disrupted their coastal habitat sufficiently to cause starving birds to move south on the Labrador Current as far as Florida. Despite the continuation of anomalously warm ocean temperatures in subsequent years and a reduction in plankton communities in the Bay of Fundy and Gulf of Maine that continues to date, no comparable events have been recorded in subsequent winters; this supports our theory that the delayed effects of Hurricane Sandy contributed to these wrecks. We highlight the power of these datasets to detect and to investigate birds' responses to extreme and anomalous conditions, which in turn provides insight into the dynamics of rapidly changing ecological systems. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and has been established as a risk factor for neurodegenerative diseases such as Alzheimer's disease (AD). Neurofibrillary tangles (NFTs), aggregates of intracellular tau, are hallmarks of AD and are observed in the post‐TBI brain; however, the mechanisms that contribute to tau aggregation and accumulation are not well understood. One key mechanism that may contribute to this tau aggregation is decreased clearance by the glymphatic system, a perivascular pathway that clears solutes, including tau, from the brain. Method: PS19 mice with tau pathology were crossed with Aqp4−/− mice lacking the astroglial water channel aquaporin‐4 (AQP4) or Snta1−/− mice lacking perivascular localization of AQP4. Behavioral tests were performed on the PS19Aqp4 transgenic crosses at 4 months or 6 months of age. Brain tissue was collected and stained for markers of p‐tau pathology. A mild closed‐skull controlled cortical impact TBI model was established and validated. Sham or TBIs were performed on PS19Snta1 transgenic crosses at 3 months of age. Behavioral testing was performed at 4 months (1 month post‐TBI) or 6 months (3 month post‐TBI). Brain tissue was collected and stained for markers of p‐tau pathology. Result: We confirmed the previous finding that glymphatic influx is impaired following a closed‐head controlled cortical impact TBI. We also observed that Aqp4 deletion was sufficient to exacerbate tau pathology in PS19 mice at 6 months old, in the absence of TBI, and more advanced tau pathology was observed in PS19+Snta1−/‐ mice at 6 months old (3 months post‐TBI) compared to PS19+Snta+/+ that also received a TBI. Conclusion: Loss of AQP4 or loss of perivascular AQP4 promotes tau pathology in a mouse model of tau pathology. These studies may provide a mechanistic basis for the vulnerability of the post‐traumatic brain to tau aggregation and neurodegeneration and suggest that targeting glymphatic dysfunction may be useful in the prevention and treatment of neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: The reduced clearance of amyloid‐beta (Aβ) is thought to contribute to the development of Alzheimer's disease (AD) pathology, characterized by the deposition of Aβ plaques. Previous studies have shown that Aβ is cleared via the glymphatic system, a brain‐wide network of perivascular pathways that support exchange between cerebrospinal fluid and interstitial fluid within the brain. Such exchange is mediated by the water channel aquaporin‐4 (AQP4), localized at astrocytic endfeet. Research has found that the deletion or mislocalization of Aqp4 is associated with reduced Aβ clearance and, in turn, Aβ plaque formation. Method: In this study, we evaluated how the deposition of Aβ plaques within a 5xFAD mouse model is impacted by either the mislocalization or deletion of perivascular AQP4. We utilized both the AQP4 knockout mouse and α‐syntrophin (Snta1) knockout mouse, which lacks perivascular AQP4 localization, and crossed them with a mouse model line of amyloidosis (5xFAD) to determine the effect on Aβ deposition. Mice were perfused at 18 weeks and amyloid‐beta, AQP4, and lectin were assessed by immunofluorescence. Amyloid β distribution was evaluated anterior to posterior through the brain utilizing regions of interests for entire slice, cortex, corpus callosum, hippocampus, subiculum, sub cortical structures, and amygdala when applicable. Result: We observed that both the absence (Aqp4KO) and mislocalization (Snta1KO) of AQP4 significantly increases amyloid distribution across the brain, when compared with 5xFAD littermate controls. Further, the mislocalization of AQP4 resulted in a significant increase in the size of Aβ plaque deposition not present with AQP4 deletion. Conclusion: s highlights that the mislocalization of perivascular AQP4 has a greater impact on increased amyloid burden than the deletion of AQP4. In suggesting that the mechanism of AQP4 mislocalization may lie upstream of amyloid or tau pathology, targeting perivascular AQP4 localization may be provide a novel pathway toward secondary, or potentially primary prevention of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Activated neutrophils eject neutrophil extracellular traps (NETs) consisting of web‐like structures of DNA, histones, and granular proteins. Neutrophils traffic into the brain in Alzheimer's disease (AD) and along with NETs are associated with amyloid beta (Aβ) plaques. However, whether NETs may impair glymphatic clearance of Aβ has never been examined. The glymphatic system is a network of perivascular pathways that provides a pathway for solutes to be cleared from the brain interstitium. Impairment of glymphatic function promotes Aβ plaque deposition. We proposed that NETs may decrease glymphatic exchange by impairing perivascular and interstitial fluid movement, resulting in impaired Aβ clearance. Method: 5XFAD mice with amyloid pathology were crossed with Pad4−/− mice lacking the ability to form NETs, generating 5XFAD mice lacking NET formation. Barnes maze, spontaneous alternation Y maze, and open field behavioral tests were performed on 5XFAD+Pad4+/+ and 5XFAD+Pad4−/− mice at 4 months old. The following week, tracer was intracisternally injected into the CSF and dynamic transcranial imaging was performed to measure tracer movement over the cortical surface. Brains were then collected after 45 minutes. Tracer influx was quantified in these brain slices and the tissue was stained for amyloid beta, GFAP, Iba1, and neutrophil markers. Result: Pad4 gene deletion in a 5XFAD mouse model of amyloid pathology improved tracer influx, decreased amyloid burden, and improved cognitive function. Conclusion: NETs promote glymphatic impairment, amyloid accumulation, and cognitive impairment in a mouse model of amyloid pathology. These studies highlight the important role that neutrophils and NETs play in the pathology of AD and may be a novel therapeutic target. [ABSTRACT FROM AUTHOR]

The article presents a study on records of Asian white-winged scoter in Alaska. It discusses three taxa of the category Melanitta including fusca or Velvet Scoter, deglandi or White-winged Scoter, and stejnegeri or Stejneger's Scoter, their origin and nesting behaviors. It differentiates features of adult males of the east Asian stejnegeri from the American deglandi. It analyses why that the species stejnegeri was retained as a subspecies of M. deglandi. It references records of adult male stejnegari species observed in Saint Lawrence Island and Nome.

Abstract: Background: In several recent papers it has been suggested that HIV prevalence and incidence are declining in Zimbabwe as a result of changing sexual behavior. We provide further support for these suggestions, based on an analysis of more extensive, age-stratified, HIV prevalence data from 1990 to 2009 for perinatal women in Harare, as well as data on incidence and mortality. Methodology/principal findings: Pooled prevalence, incidence and mortality were fitted using a simple susceptible-infected (SI) model of HIV transmission; age-stratified prevalence data were fitted using double-logistic functions. We estimate that incidence peaked at 5.5% per year in 1991 declining to 1% per year in 2010. Prevalence peaked in 1998/9 [35.9% (CI95: 31.3–40.7)] and decreased by 67% to 11.9% (CI95: 10.1–13.8) in 2009. For women <20y, 20–24y, 25–29y, 30–34y and ≥35y, prevalence peaked at 25.4%, 34.2%, 47.1%, 44.0% and 33.5% in 1993, 1996, 1997, 1998 and 1999, respectively, declining thereafter in every age group. Among women <25y, prevalence peaked in 1994 at 28.8% declining thereafter by 69% to 8.9% (CI95: 6.8–11.5) in 2009. Conclusion/significance: HIV prevalence declined substantially among perinatal women in Harare after 1998 consequent upon a decline in incidence starting in the early 1990s. Our model suggests that this was primarily a result of changes in behavior which we attribute to a general increase in awareness of the dangers of AIDS and the ever more apparent increases in mortality. [Copyright &y& Elsevier]

Objectives: The relationship between Fe status and HIV infection is complex and poorly understood. While anaemia is a major complication of HIV infection, higher Fe stores may be associated with disease progression. There is limited and conflicting data available from Africa. Design: Cross-sectional and prospective cohort study. Setting, subjects and methods: We examined the association between postpartum Fe status (Hb, serum ferritin (SF) and transferrin receptor (TfR)) and viral load (VL) and HIV-related mortality in 643 HIV-positive Zimbabwean women over a period of 12 months. Results: In non-anaemic women a log10 increase in SF was associated with a 2·3-fold increase in VL (P=0·019); this association was absent in anaemic women. In prospective analyses, a log10 increase in SF was associated with a 4-fold increase in mortality by 12 months (P=0η002). Hb was negatively associated with VL (P=0·001) and mortality (P=0·047). The adverse associations between SF and both VL and mortality were found at SF concentrations >45 μg/l (P<0·05). Controlling for α1 acid glycoprotein, a marker of inflammation, attenuated the association between both SF and VL and mortality, but these remained significant. Conclusions: These results are consistent with the hypothesis that high Fe stores have adverse consequences in HIV infection. If adverse consequences are real, our data suggest that they occur at SF concentrations exceeding those consistent with adequate Fe nutriture. [ABSTRACT FROM AUTHOR]

Twenty seven babies with severe non-haemolytic hydrops fetalis were born during a 7 1/4 year period (1/1400 total births). Thirteen were live born and admitted to the intensive care nursery, but only three survived. The survivors differed from those live born infants who died in the neonatal period in that the cause of the hydrops was discovered antenatally, their serum concentrations of total protein and albumin were normal, and they had no structural anomaly. A scheme of investigation of the severely hydropic fetus in the antenatal period is outlined and the role of active obstetric management is evaluated. [ABSTRACT FROM AUTHOR]