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Sleep disturbance is a recognized risk factor for Alzheimer's disease (AD), but the underlying micro-pathological evidence remains limited. To bridge this gap, we established an amyloid-β oligomers (AβO)-induced rat model of AD and subjected it to intermittent sleep deprivation (SD). Diffusion tensor imaging (DTI) and transmission electron microscopy were employed to assess white matter (WM) integrity and ultrastructural changes in myelin sheaths. Our findings demonstrated that SD exacerbated AβO-induced cognitive decline. Furthermore, we found SD aggravated AβO-induced asymmetrical impairments in WM, presenting with reductions in tract integrity observed in commissural fibers and association fasciculi, particularly the right anterior commissure, right corpus callosum, and left cingulum. Ultrastructural changes in myelin sheaths within the hippocampus and corpus callosum further confirmed a lateralized effect. Moreover, SD worsened AβO-induced lateralized disruption of the brain structural network, with impairments in critical nodes of the left hemisphere strongly correlated with cognitive dysfunction. This work represents the first identification of a lateralized impact of SD on the mesoscopic network and cognitive deficits in an AD rat model. These findings could deepen our understanding of the complex interplay between sleep disturbance and AD pathology, providing valuable insights into the early progression of the disease, as well as the development of neuroimaging biomarkers for screening early AD patients with self-reported sleep disturbances. Enhanced understanding of these mechanisms may pave the way for targeted interventions to alleviate cognitive decline and improve the quality of life for individuals at risk of or affected by AD. a AβO injection and sleep deprivation were conducted on adult rats. b Sleep deprivation and AβO-induced neurotoxicity aggravated cognitive disability with a synergistic effect. c Sleep deprivation and AβO-induced neurotoxicity reduced the integrity of specific association fasciculi and commissural fibers with ultrastructural demyelination. d On the basis of white matter integrity destruction, the structural connection was disrupted. The exacerbated topological properties with lateralized effects were correlated with cognitive decline. [ABSTRACT FROM AUTHOR]

Neurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8–11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (< 10 min), were assessed by the weighted Youden index (Jw, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p < 0.01) after 10 min of CPR. Change in [HbO2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR. [ABSTRACT FROM AUTHOR]

Background: Diffuse correlation spectroscopy (DCS) noninvasively permits continuous, quantitative, bedside measurements of cerebral blood flow (CBF). To test whether optical monitoring (OM) can detect decrements in CBF producing cerebral hypoxia, we applied the OM technique continuously to probe brain-injured patients who also had invasive brain tissue oxygen (PbO2) monitors.Methods: Comatose patients with a Glasgow Coma Score (GCS) < 8) were enrolled in an IRB-approved protocol after obtaining informed consent from the legally authorized representative. Patients underwent 6-8 h of daily monitoring. Brain PbO2 was measured with a Clark electrode. Absolute CBF was monitored with DCS, calibrated by perfusion measurements based on intravenous indocyanine green bolus administration. Variation of optical CBF and mean arterial pressure (MAP) from baseline was measured during periods of brain hypoxia (defined as a drop in PbO2 below 19 mmHg for more than 6 min from baseline (PbO2 > 21 mmHg). In a secondary analysis, we compared optical CBF and MAP during randomly selected 12-min periods of "normal" (> 21 mmHg) and "low" (< 19 mmHg) PbO2. Receiver operator characteristic (ROC) and logistic regression analysis were employed to assess the utility of optical CBF, MAP, and the two-variable combination, for discrimination of brain hypoxia from normal brain oxygen tension.Results: Seven patients were enrolled and monitored for a total of 17 days. Baseline-normalized MAP and CBF significantly decreased during brain hypoxia events (p < 0.05). Through use of randomly selected, temporally sparse windows of low and high PbO2, we observed that both MAP and optical CBF discriminated between periods of brain hypoxia and normal brain oxygen tension (ROC AUC 0.761, 0.762, respectively). Further, combining these variables using logistic regression analysis markedly improved the ability to distinguish low- and high-PbO2 epochs (AUC 0.876).Conclusions: The data suggest optical techniques may be able to provide continuous individualized CBF measurement to indicate occurrence of brain hypoxia and guide brain-directed therapy. [ABSTRACT FROM AUTHOR]

Strengths-based strategies to reduce youth violence in low-resource urban communities are urgently needed. Supportive adolescent-adult relationships may confer protection, but studies have been limited by self-reported composite outcomes. We conducted a population-based case-control study among 10- to 24-year-old males in low-resource neighborhoods to examine associations between supportive adult connection and severe assault injury. Cases were victims of gunshot assault injury (n = 143) and non-gun assault injury (n = 206) from two level I trauma centers. Age- and race-matched controls (n = 283) were recruited using random digit dial from the same catchment. Adolescent-adult connections were defined by: (1) brief survey questions and (2) detailed family genograms. Analysis used conditional logistic regression. There were no significant associations between positive adult connection, as defined by brief survey questions, and either gunshot or non-gun assault injury among adolescents with high prior violence involvement (GSW OR = 2.46, 95% CI 0.81-7.49; non-gun OR = 1.59, 95% CI 0.54-4.67) or low prior violence involvement (GSW OR = 0.92, 95% CI 0.34-2.44; non-gun OR = 1.96, 95% CI 0.73-5.28). In contrast, among adolescents with high levels of prior violence involvement, reporting at least one supportive adult family member in the family genogram was associated with higher odds of gunshot assault injury (OR = 4.01, 95% CI 1.36-11.80) and non-gun assault injury (OR = 4.22, 95% CI 1.48-12.04). We were thus unable to demonstrate that positive adult connections protected adolescent males from severe assault injury in this highly under-resourced environment. However, at the time of injury, assault-injured adolescents, particularly those with high prior violence involvement, reported high levels of family support. The post-injury period may provide opportunities to intervene to enhance and leverage family connections to explore how to better safeguard adolescents. [ABSTRACT FROM AUTHOR]

We are motivated by the chronic renal insufficiency cohort (CRIC) study to identify risk factors for renal progression in patients with chronic kidney diseases. The CRIC study collects two types of renal outcomes: glomerular filtration rate (GFR) estimated annually and end-stage renal disease (ESRD). A related outcome of interest is death which is a competing event for ESRD. A joint modeling approach is proposed to model a longitudinal outcome and two competing survival outcomes. We assume multivariate normality on the joint distribution of the longitudinal and survival outcomes. Specifically, a mixed effects model is fit on the longitudinal outcome and a linear model is fit on each survival outcome. The three models are linked together by having the random terms of the mixed effects model as covariates in the survival models. EM algorithm is used to estimate the model parameters, and the nonparametric bootstrap is used for variance estimation. A simulation study is designed to compare the proposed method with an approach that models the outcomes sequentially in two steps. We fit the proposed model to the CRIC data and show that the protein-to-creatinine ratio is strongly predictive of both estimated GFR and ESRD but not death. [ABSTRACT FROM AUTHOR]

We propose a new model for non-stationary random processes to represent time series with a time-varying spectral structure. Our SLEX model can be considered as a discrete time-dependent Cramér spectral representation. It is based on the so-called Smooth Localized complex EXponential basis functions which are orthogonal and localized in both time and frequency domains. Our model delivers a finite sample size representation of a SLEX process having a SLEX spectrum which is piecewise constant over time segments. In addition, we embed it into a sequence of models with a limit spectrum, a smoothly in time varying “evolutionary” spectrum. Hence, we develop the SLEX model parallel to the Dahlhaus (1997, Ann. Statist., 25, 1–37) model of local stationarity, and we show that the two models are asymptotically mean square equivalent. Moreover, to define both the growing complexity of our model sequence and the regularity of the SLEX spectrum we use a wavelet expansion of the spectrum over time. Finally, we develop theory on how to estimate the spectral quantities, and we briefly discuss how to form inference based on resampling (bootstrapping) made possible by the special structure of the SLEX model which allows for simple synthesis of non-stationary processes. [ABSTRACT FROM AUTHOR]

Magnesium nitride (Mg3N2) was synthesized by the reaction of magnesium in the highly reactive form (Mg*) with nitrogen at 450°C under normal pressure. The effect of doping with nickel dichloride on the nitridation of Mg* was investigated. Differential thermal analysis (DTA) of Mg* systems and transmission electron microscopy (TEM) measurement of the product formed were carried out. TEM measurement showed that the particle size of the Mg3N2 synthesized was in the nanometric range. The dependence of nitridation of the NiCl2-doped Mg* on temperature was investigated at temperatures ranging from 300 to 500°C. The nitridation of NiCl2-doped Mg* could occur even at temperature as low as 300°C. [ABSTRACT FROM AUTHOR]