Brain Fluid Clearance After Traumatic Brain Injury Measured Using Dynamic Positron Emission Tomography.

Brain fluid clearance by pathways including the recently described paravascular glymphatic system is a critical homeostatic mechanism by which metabolic products, toxins, and other wastes are removed from the brain. Brain fluid clearance may be especially important after traumatic brain injury (TBI), when blood, neuronal debris, inflammatory cells, and other substances can be released and/or deposited. Using a non-invasive dynamic positron emission tomography (PET) method that models the rate at which an intravenously injected radiolabeled molecule (in this case 11C-flumazenil) is cleared from ventricular cerebrospinal fluid (CSF), we estimated the overall efficiency of brain fluid clearance in humans who had experienced complicated-mild or moderate TBI 3-6 months before neuroimaging (n = 7) as compared to healthy controls (n = 9). While there was no significant difference in ventricular clearance between TBI subjects and controls, there was a significant group difference in dependence of ventricular clearance upon tracer delivery/blood flow to the ventricles. Specifically, in controls, ventricular clearance was highly, linearly dependent upon blood flow to the ventricle, but this relation was disrupted in TBI subjects. When accounting for blood flow and group-specific alterations in blood flow, ventricular clearance was slightly (non-significantly) increased in TBI subjects as compared to controls. Current results contrast with past studies showing reduced glymphatic function after TBI and are consistent with possible differential effects of TBI on glymphatic versus non-glymphatic clearance mechanisms. Further study using multi-modal methods capable of assessing and disentangling blood flow and different aspects of fluid clearance is needed to clarify clearance alterations after TBI.

Combining Blood-Based Biomarkers and Structural MRI Measurements to Distinguish Persons with and without Significant Amyloid Plaques.

Background: Amyloid-ß (Aß) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing Aß plaques more affordably. We have previously proposed an MRI-based hippocampal morphometry measure to be an indicator of Aß plaques. Objective: To develop and validate an integrated model to predict brain amyloid PET positivity combining MRI feature and plasma Aß42/40 ratio. Methods: We extracted hippocampal multivariate morphometry statistics from MR images and together with plasma Aß42/40 trained a random forest classifier to perform a binary classification of participant brain amyloid PET positivity. We evaluated the model performance using two distinct cohorts, one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score. Results: Results from ADNI (mean age 72.6, Aß+ rate 49.5%) and BAI (mean age 66.2, Aß+ rate 36.9%) datasets revealed the integrated multimodal (IMM) model's superior performance over unimodal models. The IMM model achieved prediction accuracies of 0.86 in ADNI and 0.92 in BAI, surpassing unimodal models based solely on structural MRI (0.81 and 0.87) or plasma Aß42/40 (0.73 and 0.81) predictors. CONCLUSIONS: Our IMM model, combining MRI and BBBM data, offers a highly accurate approach to predict brain amyloid PET positivity. This innovative multiplex biomarker strategy presents an accessible and cost-effective avenue for advancing Alzheimer's disease diagnostics, leveraging diverse pathologic features related to Aß plaques and structural MRI.

[1-11C]-Butanol Positron Emission Tomography reveals an impaired brain to nasal turbinates pathway in aging amyloid positive subjects.

BACKGROUND: Reduced clearance of cerebrospinal fluid (CSF) has been suggested as a pathological feature of Alzheimer's disease (AD). With extensive documentation in non-human mammals and contradictory human neuroimaging data it remains unknown whether the nasal mucosa is a CSF drainage site in humans. Here, we used dynamic PET with [1-11C]-Butanol, a highly permeable radiotracer with no appreciable brain binding, to test the hypothesis that tracer drainage from the nasal pathway reflects CSF drainage from brain. As a test of the hypothesis, we examined whether brain and nasal fluid drainage times were correlated and affected by brain amyloid. METHODS: 24 cognitively normal subjects (≥ 65 years) were dynamically PET imaged for 60 min. using [1-11C]-Butanol. Imaging with either [11C]-PiB or [18F]-FBB identified 8 amyloid PET positive (Aß+) and 16 Aß- subjects. MRI-determined regions of interest (ROI) included: the carotid artery, the lateral orbitofrontal (LOF) brain, the cribriform plate, and an All-turbinate region comprised of the superior, middle, and inferior turbinates. The bilateral temporalis muscle and jugular veins served as control regions. Regional time-activity were used to model tracer influx, egress, and AUC. RESULTS: LOF and All-turbinate 60 min AUC were positively associated, thus suggesting a connection between the brain and the nose. Further, the Aß+ subgroup demonstrated impaired tracer kinetics, marked by reduced tracer influx and slower egress. CONCLUSION: The data show that tracer kinetics for brain and nasal turbinates are related to each other and both reflect the amyloid status of the brain. As such, these data add to evidence that the nasal pathway is a potential CSF drainage site in humans. These data warrant further investigation of brain and nasal contributions to protein clearance in neurodegenerative disease.

[Discussion on the surgical timing of rupture and hemorrhage of renal angiomyolipoma].

OBJECTIVE: To investigate the effect of different surgical timing on the surgical treatment of renal angiomyolipoma (RAML) with rupture and hemorrhage. METHODS: The demographic data and perioperative data of 31 patients with rupture and hemorrhage of RAML admitted to our medical center from June 2013 to February 2023 were collected. The surgery within 7 days after hemorrhage was defined as a short-term surgery group, the surgery between 7 days and 6 months after hemorrhage was defined as a medium-term surgery group, and the surgery beyond 6 months after hemorrhage was defined as a long-term surgery group. The perioperative related indicators among the three groups were compared. RESULTS: This study collected 31 patients who underwent surgical treatment for RAML rupture and hemorrhage, of whom 13 were males and 18 were females, with an average age of (46.2±11.3) years. The short-term surgery group included 7 patients, the medium-term surgery group included 12 patients and the long-term surgery group included 12 patients. In terms of tumor diameter, the patients in the long-term surgery group were significantly lower than those in the recent surgery group [(6.6±2.4) cm vs. (10.0±3.0) cm, P=0.039]. In terms of operation time, the long-term surgery group was significantly shorter than the mid-term surgery group [(157.5±56.8) min vs. (254.8±80.1) min, P=0.006], and there was no significant difference between other groups. In terms of estimated blood loss during surgery, the long-term surgery group was significantly lower than the mid-term surgery group [35 (10, 100) mL vs. 650 (300, 1 200) mL, P < 0.001], and there was no significant difference between other groups. In terms of intraoperative blood transfusion, the long-term surgery group was significantly lower than the mid-term surgery group [0 (0, 0) mL vs. 200 (0, 700) mL, P=0.014], and there was no significant difference between other groups. In terms of postoperative hospitalization days, the long-term surgery group was significantly lower than the mid-term surgery group [5 (4, 7) d vs. 7 (6, 10) d, P=0.011], and there was no significant difference between other groups. CONCLUSION: We believe that for patients with RAML rupture and hemorrhage, reoperation for more than 6 months is a relatively safe time range, with minimal intraoperative bleeding. Therefore, it is more recommended to undergo surgical treatment after the hematoma is systematized through conservative treatment.

APOE ε4 is associated with decreased synaptic density in cognitively impaired participants.

INTRODUCTION: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18 F-florbetapir and synaptic density PET with 18 F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4-associated synaptic density loss were analyzed. RESULTS: Compared with non-carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aß) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype. DISCUSSION: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.

Early postnatal moderate catch­up growth in rats with nutritional intrauterine growth restriction preserves pulmonary vascular and cognitive function in adulthood.

Intrauterine growth restriction (IUGR) with rapid postnatal catch-up growth is strongly associated with pulmonary vascular dysfunction in adulthood, whereas IUGR with delayed growth in early postnatal life results in long-term brain deficits. In the present study, it was hypothesized that IUGR with early moderate catch-up growth may alleviate pulmonary vascular remodeling in adulthood without affecting memory function. An IUGR model was established by restricting maternal nutrition during pregnancy. Different growth patterns were achieved by adjusting the litter size in each group during lactation. Rats meeting the weight requirement at weaning were selected for subsequent studies at three time points (3, 9 and 13 weeks). Cognitive function was evaluated using a Y-maze. Invasive hemodynamic measurements were conducted to measure the mean pulmonary arterial pressure (mPAP). In addition, primary pulmonary artery smooth muscle cells (PASMCs) and pulmonary vascular endothelial cells (PVECs) were cultured to investigate their role in the increase in mPAP following rapid catch-up growth. The results showed that memory function deficits in the rats in the delayed growth group were associated with reduced proliferation of neural stem cells in the subgranular zone of the hippocampus. Furthermore, moderate catch-up growth at the three time points improved memory function while maintaining a normal mPAP. In adult IUGR rats experiencing rapid catch-up growth, although memory function improved, elevated mPAP and medial thickening of pulmonary arterioles were observed. Additionally, PASMCs exhibited excessive proliferation, migration and anti-apoptotic activity in the rapid catch-up group, and PVECs also displayed excessive proliferation. These results suggested that moderate catch-up growth after IUGR is a better strategy for optimal cognition and cardiovascular health in adulthood compared with rapid catch-up growth or delayed growth.

In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation.

The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.

Role of low-density lipoprotein electronegativity and sexual dimorphism in contributing early ventricular tachyarrhythmias following ST-elevation myocardial infarction.

Background: Early ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI. Methods: We analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms. An ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE-/- mice fed a high-fat diet to explore the underlying mechanisms of early VT/VF. Results: In 255 of out 2,964 STEMI patients who experienced early VT/VF, the age was younger (58.6 ± 13.8 vs. 61.0 ± 13.0 years old, P = 0.008) with a male predominance. The plasma levels of L5, the most electronegative subclass of low-density lipoprotein, was higher in early VT/VF patients compared to those without early VT/VF (n = 21, L5: 14.1 ± 22.6% vs. n = 46, L5: 4.3 ± 9.9%, P = 0.016). In the experimental setup, all male mice (n = 4) developed VT/VF post sham operation, whereas no such incidence was observed in the female mice (n = 3). Significantly, male mice exhibited considerably slower cardiac conduction velocity as compared to their female counterparts in whole heart preparations (25.01 ± 0.93 cm/s vs.42.32 ± 5.70 cm/s, P < 0.001), despite analogous action potential durations. Furthermore, isolated ventricular myocytes from male mice showed a distinctly lower sodium current density (-29.20 ± 3.04 pA/pF, n = 6) in comparison to female mice (-114.05 ± 6.41 pA/pF, n = 6, P < 0.001). This decreased sodium current density was paralleled by a reduced membrane expression of Nav1.5 protein (0.38 ± 0.06 vs. 0.89 ± 0.09 A.U., P < 0.001) and increased cytosolic Nav1.5 levels (0.59 ± 0.06 vs. 0.29 ± 0.04 A.U., P = 0.001) in male mice. Furthermore, it was observed that the overall expressions of sorting nexin 27 (SNX27) and vacuolar protein sorting 26 (VPS26) were significantly diminished in male mice as compared to female littermates (0.91 ± 0.15 vs. 1.70 ± 0.28, P = 0.02 and 0.74 ± 0.09 vs. 1.57 ± 0.13, P < 0.01, respectively). Conclusions: Our findings reveal that male STEMI patients with early VT/VF are associated with elevated L5 levels. The gender-based discrepancy in early VT/VF predisposition might be due to compromised sodium channel trafficking, possibly linked with increased LDL electronegativity.

Atrophy network mapping of clinical subtypes and main symptoms in frontotemporal dementia.

Frontotemporal Dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different FTD clinical subtypes and determine the specific localization of the network for apathy and disinhibition. Eighty FTD patients [45 behavioral variant FTD (bvFTD) and 35 semantic variant progressive primary aphasia (svPPA)] and 58 healthy controls (HCs) at Xuanwu Hospital were enrolled as Dataset 1; 112 FTD patients including 50 bvFTD, 32 svPPA, and 30 non-fluent variant PPA (nfvPPA) cases, and 110 HCs from Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) dataset were included as Dataset 2. Initially, single-subject atrophy maps were defined by comparing cortical thickness in each FTD patient versus HCs. Next, the network of brain regions functionally connected to each FTD patient's location of atrophy was determined using seed-based functional connectivity in a large (n = 1000) normative connectome. Finally, we used atrophy network mapping to define clinical subtype-specific network (45 bvFTD, 35 svPPA and 58 HCs in Dataset 1; 50 bvFTD, 32 svPPA, 30 nfvPPA and 110 HCs in Dataset 2) and symptom-specific networks [combined dataset 1 and 2, apathy without depression Vs non-apathy without depression (80:26), disinhibition Vs non-disinhibition (88:68)]. We compare the result with matched symptom networks derived from patients with focal brain lesions or conjunction analysis. Through the analysis of two datasets, we identified heterogeneity in atrophy patterns among FTD patients. However, these atrophy patterns are connected to a common brain network. The primary regions affected by atrophy in FTD included the frontal and temporal lobes, particularly the anterior temporal lobe. bvFTD connects to frontal and temporal cortical areas, svPPA mainly impacts the anterior temporal region, and nfvPPA targets the inferior frontal gyrus and precentral cortex regions. The apathy-specific network was localized in the orbital frontal cortex and ventral striatum, while the disinhibition-specific network was localized in the bilateral orbital frontal gyrus and right temporal lobe. Apathy and disinhibition atrophy networks resemble known motivational and criminal lesion networks respectively. A significant correlation was found between the apathy/disinhibition scores and functional connectivity between atrophy maps and the peak of the networks. This study localizes the common network of clinical subtypes and main symptoms in FTD, guiding future FTD neuromodulation interventions.

Prediction of the Nottingham prognostic index and molecular subtypes of breast cancer through multimodal magnetic resonance imaging.

PURPOSE: To explore the ability of intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI) and background parenchyma enhancement (BPE) to predict the Nottingham prognostic index (NPI) and molecular subtypes of breast cancer (BC). MATERIALS AND METHODS: In this study, 93 patients with BC were included, and they all underwent DKI, IVIM and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations. The corresponding mean kurtosis value (MK), pure diffusion (MD), perfusion fraction (f), pseudo diffusion coefficient (D*), true diffusion coefficient (D), and BPE were measured. We used logistic regression analysis to investigate the relevance between the NPI, molecular subtypes and variables. The diagnostic efficacy was analyzed using receiver operating characteristic curves (ROC). RESULTS: The MD and D values of the high-level NPI group were significantly lower than those of the low-level NPI group (p < 0.01), and the f value of the high-level NPI group was obviously higher than that of low-level NPI group (p < 0.001). The area under curve (AUC) of the combined model (f + D) was 0.824. Comparing with non-Luminal subtypes, the Luminal subtypes showed obviously lower MK, f and D*, and the AUC of the combined model (MK + f + D*) was 0.785. In comparison to other subtypes, the MK and D* values of triple-negative subtype were higher than other subtypes, and the combined model (MK + D*) represented an AUC of 0.865. CONCLUSION: The quantitative parameters of DKI and IVIM have vital value in predicting the NPI and molecular subtypes of BC, while BPE could not provide additional information. Besides, these combined models can obviously improve the prediction performance.

Non-contact assessment of cardiac physiology using FO-MVSS-based ballistocardiography: a promising approach for heart failure evaluation.

Continuous monitoring of cardiac motions has been expected to provide essential cardiac physiology information on cardiovascular functioning. A fiber-optic micro-vibration sensing system (FO-MVSS) makes it promising. This study aimed to explore the correlation between Ballistocardiography (BCG) waveforms, measured using an FO-MVSS, and myocardial valve activity during the systolic and diastolic phases of the cardiac cycle in participants with normal cardiac function and patients with congestive heart failure (CHF). A high-sensitivity FO-MVSS acquired continuous BCG recordings. The simultaneous recordings of BCG and electrocardiogram (ECG) signals were obtained from 101 participants to examine their correlation. BCG, ECG, and intracavitary pressure signals were collected from 6 patients undergoing cardiac catheter intervention to investigate BCG waveforms and cardiac cycle phases. Tissue Doppler imaging (TDI) measured cardiac time intervals in 51 participants correlated with BCG intervals. The BCG recordings were further validated in 61 CHF patients to assess cardiac parameters by BCG. For heart failure evaluation machine learning was used to analyze BCG-derived cardiac parameters. Significant correlations were observed between cardiac physiology parameters and BCG's parameters. Furthermore, a linear relationship was found betwen IJ amplitude and cardiac output (r = 0.923, R2 = 0.926, p < 0.001). Machine learning techniques, including K-Nearest Neighbors (KNN), Decision Tree Classifier (DTC), Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), and XGBoost, respectively, demonstrated remarkable performance. They all achieved average accuracy and AUC values exceeding 95% in a five-fold cross-validation approach. We establish an electromagnetic-interference-free and non-contact method for continuous monitoring of the cardiac cycle and myocardial contractility and measure the different phases of the cardiac cycle. It presents a sensitive method for evaluating changes in both cardiac contraction and relaxation in the context of heart failure assessment.

Ddx5 Targeted Epigenetic Modification of Pericytes in Pulmonary Hypertension Following Intrauterine Growth Restriction.

Newborns with intrauterine growth restriction (IUGR) have a higher likelihood of developing pulmonary arterial hypertension (PAH) in adulthood. While there is increasing evidence suggesting that pericytes play a role in regulating myofibroblast transdifferentiation and angiogenesis in malignant and cardiovascular diseases, their involvement in the pathogenesis of IUGR-related PH and the underlying mechanisms remain incompletely understood. To address this issue, a study was conducted utilizing a Sprague-Dawley (SD) rat model of IUGR-related PH. Our investigation revealed increased proliferation and migration of pulmonary microvascular pericytes in IUGR-related PH, accompanied by weakened endothelial-pericyte interactions. Through whole transcriptome sequencing, DEAD-box protein 5(DDX5) was identified as one of the hub genes in pericytes. DDX5, a member of the RNA helicase family, plays a role in the regulation of ATP-dependent RNA helicase activities and cellular function. MicroRNAs have been implicated in the pathogenesis of PAH, and microRNA-205(miR-205) regulates cell proliferation, migration, and angiogenesis. The results of dual-luciferase reporter assays confirmed the specific binding of miR-205 to Ddx5. Mechanistically, miR-205 negatively regulates Ddx5, leading to the degradation of ß-catenin by inhibiting the phosphorylation of Gsk3ß at serine 9. In vitro experiments showed the addition of miR-205 effectively ameliorated pericyte dysfunction. Furthermore, in vivo experiments demonstrated that miR-205 agomir could ameliorate PH. Our findings indicated that the downregulation of miR-205 expression mediates pericyte dysfunction through the activation of Ddx5. Therefore, targeting the miR-205/Ddx5/p-Gsk3ß/ß-catenin axis could be a promising therapeutic approach for IUGR-related PH.

Harmonizing florbetapir and PiB PET measurements of cortical Aß plaque burden using multiple regions-of-interest and machine learning techniques: An alternative to the Centiloid approach.

INTRODUCTION: Machine learning (ML) can optimize amyloid (Aß) comparability among positron emission tomography (PET) radiotracers. Using multi-regional florbetapir (FBP) measures and ML, we report better Pittsburgh compound-B (PiB)/FBP harmonization of mean-cortical Aß (mcAß) than Centiloid. METHODS: PiB-FBP pairs from 92 subjects in www.oasis-brains.org and 46 in www.gaain.org/centiloid-project were used as the training/testing sets. FreeSurfer-extracted FBP multi-regional Aß and actual PiB mcAß in the training set were used to train ML models generating synthetic PiB mcAß. The correlation coefficient (R) between the synthetic/actual PiB mcAß in the testing set was assessed. RESULTS: In the testing set, the synthetic/actual PiB mcAß correlation R = 0.985 (R2  = 0.970) using artificial neural network was significantly higher (p ≤ 6.6e-4) than the FBP/PiB correlation R = 0.927 (R2  = 0.860), improving total variance percentage (R2 ) from 86% to 97%. Other ML models such as partial least square, ensemble, and relevance vector regressions also improved R (p = 9.677e-05 /0.045/0.0017). DISCUSSION: ML improved mcAß comparability. Additional studies are needed for the generalizability to other amyloid tracers, and to tau PET. Highlights Centiloid is a calibration of the amyloid scale, not harmonization. Centiloid unifies the amyloid scale without improving inter-tracer association (R2 ). Machine learning (ML) can harmonize the amyloid scale by improving R2 . ML harmonization maps multi-regional florbetapir SUVRs to PiB mean-cortical SUVR. Artificial neural network ML increases Centiloid R2 from 86% to 97%.

Characterization of key bitter compounds in Idesia polycarpa var. vestita Diels fruit by sensory-guided fractionation.

Idesia polycarpa var. vestita Diels (I. vestita) has become a promising oil crop due to its easily digestible and highly nutritious fruit oil. However, the intense bitter taste of its fruit greatly limits its development and promotion in the food industry. Herein, five key bitter compounds from I. vestita fruit were isolated by sensory-guided fractionation and characterized using ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometer and nuclear magnetic resonance. The bitter taste of the identified compounds was subsequently validated by threshold tests and computational molecular docking. The bitterness threshold in water of idesin was the lowest (12.051 mg/L), and all bitter substances spontaneously bound to the bitter receptors hTAS2R16 and hTAS2R14, with a stronger affinity for the latter (approximately -6.5 - -9.0 kcal/mol). This is the first systematic study of bitter compounds in I. vestita fruit, providing a scientific basis for revealing the mechanism of bitterness formation and bitterness control.

Joint contributions from brain activity and activity-independent functional connectivity to working memory aging.

Working memory (WM) impairment has been well characterized in normal aging. Various studies have explored changes in either the regional activity or the interregional connectivity underlying the aging process of WM. We proposed that brain activity and connectivity would independently alter with aging and affect WM performance. WM was assessed with a classical N-back task during functional magnetic resonance imaging in a community-based sample comprising 168 elderly subjects (aged 55-86 years old). Following the rationale of background functional connectivity, we assessed age-related alterations in brain activity and seed-based interregional connectivity independently. Analyses revealed age-related decrease in positive activity of the inferior parietal lobule (IPL) and an increase in the negative activity of the ventral anterior cingulate cortex (ACC), and the local functional dysfunctions were accompanied by alterations in their connectivity to other cortical regions. Importantly, regional activity impairments in the IPL and ACC could mediate age-related effects on accuracy rate and reaction time, respectively, and those effects were further counterbalanced by enhancement of their background functional connectivity. We thus claimed that age-induced alterations in regional activity and interregional connectivity occurred independently and contributed to WM changes in aging. Our findings presented the way brain activity and functional connectivity interact in the late adulthood, thus providing a new perspective for understanding WM and cognitive aging.

Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project.

INTRODUCTION: Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project. METHOD: We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same-age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES). RESULTS: Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p < 0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups. DISCUSSION: Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.

Correlation studies of Hippocampal Morphometry and Plasma NFL Levels in Cognitively Unimpaired Subjects.

Alzheimer's disease(AD) is being the burden of society and family. Applying computing-aided strategies to reveal its pathology is one of the research highlights. Plasma neurofilament light (NFL) is an emerging noninvasive and economic biomarker for AD molecular pathology. It is valuable to reveal the correlations between the plasma NFL levels and neurodegeneration, especially hippcampal deformations at the preclinical stage. The negative correlation between plasma NFL levels and hippocampal volumes has been documented. However, the relationship between the plasma NFL levels and the hippocampal morphometry details at the preclinical stage is still elusive. This study seeks to demonstrate the capacity of our proposed surface-based hippocampal morphometry system to discern the plasma NFL positive (NFL+>41.9 pg/L) level and plasma NFL negative (NFL-<41.9pg/L) level and illustrate its superiority to the hippocampal volume measurement by drawing the cohort of 154 CU middle aged and elderly adults. We also apply this morphometry measure and a proposed sparse coding based classification algorithm to classify CU individuals with NFL+ and NFL- levels. Experimental results show that the proposed hippocampal morphometry system offers stronger statistical power to discriminate CU subjects with NFL+ and NFL- levels, comparing with the hippocampal volume measure. Furthermore, this system can discriminate plasma NFL levels in CU individuals (Accuracy=0.86). Both the group level and individual level analysis results indicate that the association between plasma NFL levels and the hippocampal shapes can be mapped at the preclinical stage.

Prevention, incidence, and risk factors of chyle leak after radical nephrectomy and thrombectomy.

BACKGROUND: To define the incidence and risk factors of chyle leak (CL) after radical nephrectomy and thrombectomy and to determine the impact of chyle leak on oncological outcomes. PATIENTS AND METHODS: A total of 445 patients who underwent radical nephrectomy and thrombectomy between January 2014 and January 2023 were included. CL is defined as the drainage of chyle with a triglyceride level greater than 110 mg/dL after oral intake or enteral nutrition. Multivariate logistic regression analysis was performed to identify the risk factors of postoperative (CL). The Kaplan-Meier curves were used to compare overall survival and cancer-specific survival. RESULTS: 44 patients (9.9%) were diagnosed as (CL). All patients developed CL within 6 days after the operation with a median time of 3 days. In multivariate logistic regression analysis, Mayo grade and side were independent patient-related risk factors. In addition, operation approach, operation time, and number of lymph nodes harvested were independent surgery-related risk factors. Between the CL group and the non-CL group, neither overall survival nor cancer-specific survival showed statistical differences. CONCLUSION: Based on this retrospective study of renal cell carcinoma and tumor thrombus patients in our center, we found that the risk factors were Mayo grade, side, operation approach, operation time, and number of lymph nodes harvested, and the occurrence of CL significantly prolonged hospital stay, but had no effect on long-term oncological outcomes.

Divergent brain regional atrophy and associated fiber disruption in amnestic and non-amnestic MCI.

BACKGROUND: Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI). METHODS: T1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed. RESULTS: The aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language. CONCLUSIONS: The divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions.

Development of a Real-Time Quantitative PCR Based on a TaqMan-MGB Probe for the Rapid Detection of Theileria haneyi.

Equine piroplasmosis (EP) is a parasitic disease caused by Theileria equi (T. equi), Babesia caballi (B. caballi) and Theileria haneyi (T. haneyi). This disease is considered to be reportable by the World Organization for Animal Health (WOAH). Real-time quantitative PCR (qPCR) is regarded as a straightforward, rapid and sensitive diagnostic method to detect pathogens. However, qPCR has not been employed in the various epidemiological investigations of T. haneyi. In this study, we developed a new qPCR method to detect T. haneyi based on the chr1sco (chromosome 1 single-copy open reading frame (ORF)) gene, which has no detectable orthologs in T. equi or B. caballi. A TaqMan MGB probe was used in the development of the qPCR assay. A plasmid containing the chr1sco gene was constructed and used to establish the standard curves. The novel qPCR technique demonstrated great specificity for detecting additional frequent equine infectious pathogens and sensitivity for detecting diluted standard plasmids. This qPCR was further validated by comparison with an optimized nested PCR (nPCR) assay in the analysis of 96 clinical samples. The agreement between the nPCR assay and the established qPCR assay was 85.42%. The newly established method could contribute to the accurate diagnosis of T. haneyi infections in horses.