Venous Thromboembolism Rates in Trauma Patients Significantly Increase With Missed Prophylactic Enoxaparin Doses.

Background: Current literature demonstrates prophylactic enoxaparin to be efficacious in reducing venous thromboembolism (VTE) rates without significantly increasing risk for bleeding complications. Despite this evidence, prophylactic enoxaparin doses are frequently withheld for surgery or procedures. This exploratory study aims to quantify the risk of a VTE event in trauma patients associated with missed doses of prophylactic enoxaparin. Methods: This retrospective cohort study evaluated trauma patients admitted to our Level 1 trauma center from January 1, 2012 to January 31, 2021. A 1:1 propensity match with ten variables was performed to compare patients receiving prophylactic enoxaparin that had a VTE and those that did not. The primary outcome was a VTE event. Results: 493 patients met inclusion criteria; 1:1 propensity score matching was performed resulting in a cohort of 184 patients. The percentage of patients that missed a prophylactic enoxaparin dose in the VTE group was higher than the no VTE group (34.8% vs 21.7%, P = 0.049). This is consistent when examining total missed doses (P = 0.038) and consecutively missed doses (P = 0.035). The odds of having a VTE for patients that missed at least one dose or more of enoxaparin are nearly two times greater (OR 1.92, 95% CI 0.997, 3.7). Conclusion: Missing enoxaparin doses significantly increases the risk of VTE in matched populations. Most prophylactic enoxaparin doses were held for procedures, and not for bleeding events. Trauma teams should carefully weigh the risk of bleeding complications associated with continuing enoxaparin prophylaxis against the significant thromboembolic risk of withholding it.

Neuron-Astrocyte Interactions: A Human Perspective.

This chapter explores the intricate interactions between neurons and astrocytes within the nervous system with a particular emphasis on studies conducted in human tissue or with human cells. We specifically explore how neuron-astrocyte interactions relate to processes of cellular development, morphology, migration, synapse formation, and metabolism. These findings enrich our understanding of basic neurobiology and how disruptions in these processes are relevant to human diseases.The study of human neuron-astrocyte interactions is made possible because of transformative in vitro advancements that have facilitated the generation and sustained culture of human neural cells. In addition, the rise of techniques like sequencing at single-cell resolution has enabled the exploration of numerous human cell atlases and their comparisons to other animal model systems. Thus, the innovations outlined in this chapter illuminate the convergence and divergence of neuron-astrocyte interactions across species. As technologies progress, continually more sophisticated in vitro systems will increasingly reflect in vivo environments and deepen our command of neuron-glial interactions in human biology.

Nanoscale synchrotron x-ray analysis of intranuclear iron in melanised neurons of Parkinson's substantia nigra.

Neuromelanin-pigmented neurons of the substantia nigra are selectively lost during the progression of Parkinson's disease. These neurons accumulate iron in the disease state, and iron-mediated neuron damage is implicated in cell death. Animal models of Parkinson's have evidenced iron loading inside the nucleoli of nigral neurons, however the nature of intranuclear iron deposition in the melanised neurons of the human substantia nigra is not understood. Here, scanning transmission x-ray microscopy (STXM) is used to probe iron foci in relation to the surrounding ultrastructure in melanised neurons of human substantia nigra from a confirmed Parkinson's case. In addition to the expected neuromelanin-bound iron, iron deposits are also associated with the edge of the cell nucleolus. Speciation analysis confirms these deposits to be ferric (Fe3+) iron. The function of intranuclear iron in these cells remains unresolved, although both damaging and protective mechanisms are considered. This finding shows that STXM is a powerful label-free tool for the in situ, nanoscale chemical characterisation of both organic and inorganic intracellular components. Future applications are likely to shed new light on incompletely understood biochemical mechanisms, such as metal dysregulation and morphological changes to cell nucleoli, that are important in understanding the pathogenesis of Parkinson's.

An Improved Assessment Method to Estimate (Poly)phenol Intake in Adults with Chronic Pancreatitis.

BACKGROUND: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped. AIMS: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data. METHODS: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample. RESULTS: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively. CONCLUSIONS: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.

Ovarian vein thrombus in a pediatric patient: A case study.

Acute abdominal pain is a very common chief complaint in the pediatric population, accounting for 5-10% of emergency department (ED) visits. Etiology differentiation is determined by complete history and physical examination, basic laboratory studies, and a variety of imaging study options. In this case report, we present an 8-year-old female with an unusual etiology of acute lower abdominal pain. She presented with tachycardia, hypertension, and bilateral lower quadrant abdominal tenderness without peritonitis. Laboratory studies were unremarkable and appendix ultrasound was indeterminate. CT with contrast revealed right ovarian vein thrombosis. Hematology evaluation did not reveal hypercoagulability. She was discharged on rivaroxaban, which was discontinued after a 3 month course and negative follow-up MRI. Ovarian vein thrombosis (OVT) most commonly develops in the peripartum time frame, with an estimated 20%-40% of cases not related to pregnancies. However, patients with nonpregnancy related OVT were determined to be significantly older than patients with pregnancy related OVT. This case report demonstrates the youngest documented case of OVT. This patient was not in the peripartum period and did not have any identifiable risk factors. Given this unprovoked OVT in a pediatric patient, in patients presenting with abdominal pain with unspecified etiology, advanced imaging studies may be helpful in establishing a diagnosis.

mini-MED: study protocol for a randomized, multi-intervention, semi-controlled feeding trial of a Mediterranean-amplified vs. habitual Western dietary pattern for the evaluation of food-specific compounds and cardiometabolic health.

BACKGROUND: Diet is among the most influential lifestyle factors impacting chronic disease risk. Nutrimetabolomics, the application of metabolomics to nutrition research, allows for the detection of food-specific compounds (FSCs) that can be used to connect dietary patterns, such as a Mediterranean-style (MED) diet, to health. This validation study is based upon analyses from a controlled feeding MED intervention, where our team identified FSCs from eight foods that can be detected in biospecimens after consumption and may therefore serve as food intake biomarkers. METHODS: Individuals with overweight/obesity who do not habitually consume a MED dietary pattern will complete a 16-week randomized, multi-intervention, semi-controlled feeding study of isocaloric dietary interventions: (1) MED-amplified dietary pattern, containing 500 kcal/day from eight MED target foods: avocado, basil, cherry, chickpea, oat, red bell pepper, walnut, and a protein source (alternating between salmon or unprocessed, lean beef), and (2) habitual/Western dietary pattern, containing 500 kcal/day from six non-MED target foods: cheesecake, chocolate frozen yogurt, refined grain bread, sour cream, white potato, and unprocessed, lean beef. After a 2-week washout, participants complete four, 4-week intervention periods, with biospecimen sampling and outcome assessments at baseline and at intervention weeks 4, 8, 12, and 16. The primary outcome is change in the relative abundance of FSCs from the eight MED target foods in participant biospecimens from baseline to the end of each intervention period. Secondary outcomes include mean change in cardiometabolic health indicators, inflammatory markers, and adipokines. Exploratory outcomes include change in diversity and community composition of the gut microbiota. DISCUSSION: Our stepwise strategy, beginning with identification of FSCs in whole diets and biospecimens, followed by relating these to health indicators will lead to improved methodology for assessment of dietary patterns and a better understanding of the relationship between food and health. This study will serve as a first step toward validating candidate food intake biomarkers and allow for assessment of relationships with cardiometabolic health. The identification of food intake biomarkers is critical to future research and has implications spanning health promotion and disease prevention for many chronic conditions. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT05500976 ; Date of registration: August 15, 2022.

Longitudinal Outcomes of Malignant Ureteral Obstruction Secondary to Ovarian Cancer: Predictors of Resolution and the Role of Surgical Management.

OBJECTIVE: To review the management of ovarian cancer (OCa) associated hydronephrosis (HN). Specifically, we aim to identify optimal management of HN in the acute setting, predictors of HN resolution, and the role of surgery (tumor debulking/(+/-)ureterolysis/hysterectomy). MATERIALS/METHODS: The study cohort included OCa patients managed at our institution from 2004-2019 that developed OCa-associated HN. Initial HN management was recorded as none, retrograde ureteral stent (RUS) or percutaneous nephrostomy tube (PCN). Primary outcomes included (1) HN management failure, (2) HN management complications, and (3) HN resolution. Patient, cancer, and treatment predictors of outcomes were assessed using logistic regression and fine-Gray competing risk models. RESULTS: Of 2580 OCa patients, 190 (7.4%) developed HN. HN was treated in 121; 90 (74.4%) with RUS, 31 (25.6%) with PCN. Complication rates were similar between PCN and RUS (83% vs 85.1%; P = .79; all Clavian Grade I/II). Initial HN treatment failure occurred in 28 patients, predicted by renal atrophy (hazard ratios (HR) 3.27, P <.01). HN resolution occurred in only 52 (27%) patients and was predicted by lower International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO III/IV HR 0.42, P <.01) and surgical tumor debulking/ureterolysis (HR 2.83, P = .02). CONCLUSION: Resolution of HN associated with malignant obstruction from OCa is rare and is most closely associated with tumor debulking and International Federation of Gynecology and Obstetrics (FIGO) stage. Initial endoscopic treatment modality was not significantly associated with complications or resolution, though RUS failures were slightly more common. Ureteral reconstruction at time of debulking/ureterolysis is potentially underutilized.

Salmon Food-Specific Compounds and Their Metabolites Increase in Human Plasma and Are Associated with Cardiometabolic Health Indicators Following a Mediterranean-Style Diet Intervention.

BACKGROUND: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds that may provide cardiometabolic benefits. OBJECTIVES: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored. METHODS: For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with 2 servings of salmon per week for 2 5-wk periods. CHIs were assessed, and fasting plasma was collected pre- and postintervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to postintervention and associations with changes in CHIs. RESULTS: Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (false discovery rate <0.05). Increases in 2 annotated salmon FSCs and 2 metabolites were associated with improvements in CHIs, including total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. CONCLUSIONS: A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for the discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health. The trials supporting this work were registered at NCT02573129 (Mediterranean-style diet intervention) and NCT05500976 (ongoing clinical trial).

Ectopic transcription due to inappropriately inherited histone methylation may interfere with the ongoing function of terminally differentiated cells.

Many human neurodevelopmental disorders are caused by de novo mutations in histone modifying enzymes. These patients have craniofacial defects, developmental delay, intellectual disability and behavioral abnormalities, but it remains unclear how the mutations lead to such developmental defects. Here we take advantage of the invariant C. elegans lineage along with a unique double mutant in the H3K4me1/2 demethylase SPR-5/LSD1/KDM1A and the H3K9 methyltransferase MET-2/SETDB1 to address this question. We demonstrate that spr-5; met-2 double mutant worms have a severe chemotaxis defect that is dependent upon the ectopic expression of germline genes in somatic tissues. In addition, by performing single-cell RNAseq, we find that germline genes begin to be ectopically expression widely in spr-5; met-2 embryos. However, surprisingly we found that spr-5; met-2 mutants have no somatic lineage defects prior to the 200-cell stage of embryogenesis. This suggests that the altered chemotaxis behavior may be due to ongoing defect in terminally differentiated cells rather than a defect in development. To test this directly, we used RNAi to shut off the ectopic expression of germline genes in L2 spr-5; met-2 larvae, which have a fully formed nervous system. Remarkably, we find that shutting off the ectopic germline expression rescues normal chemotaxis behavior in the same adult worms that previously had a chemotaxis defect at the L2 stage. This suggests that ongoing ectopic transcription can block normal behavior in a fully intact nervous system. These data raise the possibility that intellectual disability and altered behavior in neurodevelopmental syndromes, caused by mutations in histone modifying enzymes, could be due to ongoing ectopic transcription and may be reversible.

Changes in Running Kinematics and Kinetics Following a 10 km Run.

Background: Little is known about changes in kinetics or kinematics following a 10 km training run. This information has implications on risk of running-related injury. Purpose: The purpose of this study was to examine the effect of a 10 km run on running kinematics and kinetics in a sample of experienced runners. Study Design: Cross-Sectional Study. Subjects: Nineteen runners ages 18-48 (7 female, 12 male) consented to participate including eight (3 female, 5 male) ultra-runners, and 11 (4 female, 7 male) recreational runners. Methods: Following collection of demographic data and completion of a short running survey, participants did a 6-minute run at their self-selected running speed to acclimate to the instrumented treadmill. Reflective markers were placed over designated anatomical landmarks on both sides of the pelvis as well as the left lower extremity and marked with a skin pen. Subjects then ran on the treadmill and 30 seconds of video data were recorded at 240 frames/sec using a high-speed camera for the sagittal plane and the frontal plane. Simultaneously, ground reaction forces (GRFs) were recorded at 1200 Hz through the treadmill's embedded force plates. Each runner then ran 10 km on a paved trail at their self-selected pace. Immediately following the run, reflective markers were reattached, guided by markings placed before the run, and a 30-second post-run trial of the video and GRF data were recorded. Video data were analyzed using Kinovea software to measure the kinematic variables of interest. Paired t-tests with Bonferroni corrections were used to find if significant differences existed between pre- and post-run data for all kinematic and kinetic variables. Results: No significant or clinically relevant differences existed between the pre- and post-run measurements for the kinematic or kinetic variables. The only significant difference noted between the ultra-runners and recreational runners was that the ultra-runners had significantly higher cadence (p=0.045). Conclusions: A 10 km run at a self-selected pace did not result in change in the mean kinematic or kinetic variables in this group of experienced runners. Ultra-runners employ higher cadence than recreational runners, but their kinematics and kinetics are similar. Level of Evidence: Level 3.

History of obstructive sleep apnea associated with incident cognitive impairment in white but not black individuals in a US national cohort study.

BACKGROUND: We sought to determine if risk for obstructive sleep apnea (OSA), a history of OSA, and/or treatment of OSA has a different association with incident cognitive impairment or cognitive decline in Black individuals and White individuals. METHODS: To determine whether the risk for OSA, a history of OSA, and/or treatment of OSA has a different association with incident cognitive impairment or cognitive decline in Black individuals and White individuals; data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) was used. Participants that completed the sleep questionnaire module, had baseline cognitive assessment, and at least one cognitive assessment during follow-up were included. Risk of OSA was determined based on Berlin Sleep Questionnaire. History of sleep apnea was determined based on structured interview questions. Optimally treated OSA was defined as treated sleep apnea as at least 4 h of continuous positive airway pressure use per night for ≥5 nights per week. RESULTS: In 19,017 participants stratified by race, White participants with history of OSA were 1.62 times more likely to have incident cognitive impairment compared to White participants without history of OSA after adjusting for demographic characteristics, history, and lifestyle factors (OR = 1.62, 95% CI = 1.05-2.50, p-value = 0.03). This relationship was not seen in Black participants (OR = 0.92, 95% CI = 0.60-1.43, p-value = 0.72). DISCUSSION: A previous diagnosis of OSA is associated with incident cognitive impairment in White Americans but not Black Americans. Further investigations are required to determine the mechanism for this difference.

Meta-analysis of skill-based and therapeutic interventions to address math anxiety.

The purpose of this meta-analysis was to examine the impact of school-based therapeutic and math skill interventions on math anxiety symptoms and math achievement among K-12 students. Potential moderators included treatment type and study quality. A systematic search yielded 17 included studies representing 1786 primary and secondary students. The results suggested that therapeutic interventions reduced math anxiety symptoms (gav = -0.51) better than math skill interventions (gav = -0.32) and math skill interventions improved math achievement (gav = 0.76) more than therapeutic interventions (gav = 0.12). Moderator analysis indicated that when accounting for study quality, the differences between intervention type were not significant for either of the outcome measures (i.e., achievement and math anxiety). Theoretical and practical implications of these findings are discussed.

The Microbiome, Epigenome, and Diet in Adults with Obesity during Behavioral Weight Loss.

Obesity has been linked to the gut microbiome, epigenome, and diet, yet these factors have not been studied together during obesity treatment. Our objective was to evaluate associations among gut microbiota (MB), DNA methylation (DNAme), and diet prior to and during a behavioral weight loss intervention. Adults (n = 47, age 40.9 ± 9.7 years, body mass index (BMI) 33.5 ± 4.5 kg/m2, 77% female) with data collected at baseline (BL) and 3 months (3 m) were included. Fecal MB was assessed via 16S sequencing and whole blood DNAme via the Infinium EPIC array. Food group and nutrient intakes and Healthy Eating Index (HEI) scores were calculated from 7-day diet records. Linear models were used to test for the effect of taxa relative abundance on DNAme and diet cross-sectionally at each time point, adjusting for confounders and a false discovery rate of 5%. Mean weight loss was 6.2 ± 3.9% at 3 m. At BL, one MB taxon, Ruminiclostridium, was associated with DNAme of the genes COL20A1 (r = 0.651, p = 0.029), COL18A1 (r = 0.578, p = 0.044), and NT5E (r = 0.365, p = 0.043). At 3 m, there were 14 unique MB:DNAme associations, such as Akkermansia with DNAme of GUSB (r = -0.585, p = 0.003), CRYL1 (r = -0.419, p = 0.007), C9 (r = -0.439, p = 0.019), and GMDS (r = -0.559, p = 0.046). Among taxa associated with DNAme, no significant relationships were seen with dietary intakes of relevant nutrients, food groups, or HEI scores. Our findings indicate that microbes linked to mucin degradation, short-chain fatty acid production, and body weight are associated with DNAme of phenotypically relevant genes. These relationships offer an initial understanding of the possible routes by which alterations in gut MB may influence metabolism during weight loss.

Identification of ligand-receptor pairs that drive human astrocyte development.

Extrinsic signaling between diverse cell types is crucial for nervous system development. Ligand binding is a key driver of developmental processes. Nevertheless, it remains a significant challenge to disentangle which and how extrinsic signals act cooperatively to affect changes in recipient cells. In the developing human brain, cortical progenitors transition from neurogenesis to gliogenesis in a stereotyped sequence that is in part influenced by extrinsic ligands. Here we used published transcriptomic data to identify and functionally test five ligand-receptor pairs that synergistically drive human astrogenesis. We validate the synergistic contributions of TGFß2, NLGN1, TSLP, DKK1 and BMP4 ligands on astrocyte development in both hCOs and primary fetal tissue. We confirm that the cooperative capabilities of these five ligands are greater than their individual capacities. Additionally, we discovered that their combinatorial effects converge in part on the mTORC1 signaling pathway, resulting in transcriptomic and morphological features of astrocyte development. Our data-driven framework can leverage single-cell and bulk genomic data to generate and test functional hypotheses surrounding cell-cell communication regulating neurodevelopmental processes.

Parkinson's disease diagnosis codes are insufficiently accurate for electronic health record research and differ by race.

BACKGROUND: There are no evidence-based guidelines for data cleaning of electronic health record (EHR) databases in Parkinson's disease (PD). Previous filtering criteria have primarily used the 9th International Statistical Classification of Diseases and Related Health Problems (ICD) with variable accuracy for true PD cases. Prior studies have not excluded atypical or drug-induced parkinsonism, and little is known about differences in accuracy by race. OBJECTIVE: To determine if excluding parkinsonism diagnoses improves accuracy of ICD-9 and -10 PD diagnosis codes. METHODS: We included ≥2 instances of an ICD-9 and/or -10 code for PD. We removed any records with at least one code indicating atypical or drug-induced parkinsonism first in all races, and then in Non-Hispanic White and Black patients. We manually reviewed 100 randomly selected charts per group before and after filtering, and performed a test of proportion (null hypothesis 0.5) for confirmed PD. RESULTS: 5633 records had ≥2 instances of a PD code. 2833 remained after filtering. The rate of true PD cases was low before and after filtering to remove parkinsonism codes (0.55 vs. 0.51, p = 0.84). Accuracy was lowest in Black patients before filtering (0.48, p = 0.69), but filtering had a greater (though modest) impact on accuracy (0.68, p < 0.001). CONCLUSIONS: There was inadequate accuracy of PD diagnosis codes in the largest study of ICD-9 and -10 codes. Accuracy was lowest in Black patients but improved the most with removing other parkinsonism codes. This highlights the limitations of using current real-world EHR data in PD research and need for further study.

Bottle mix-up: Ethanol intoxication in an infant.

Alcohol intoxication is a common ingestion in pediatrics with close to 10,000 reports to poison control centers annually. Hypoglycemia, neurological depression (ataxia, coma, nystagmus, etc.) and unstable vitals (hypothermia, hypotension, bradycardia, and respiratory depression) are common presentations. The patient is a 3 month old female who was brought into the Emergency Department (ED) for one day of decreased oral intake and inconsolability. Vital signs were reassuring. Physical exam revealed gaze preference to the right with inability to look left, dysconjugate gaze, and hypotonia. Work-up including CT of the head, and urinalysis was unremarkable. Urine drug screen was found to be positive for ethanol with follow up serum ethanol at 162 mg/dL. With conservative management the patient returned to her baseline. On follow-up with her pediatrician, it was elicited that the mother inadvertently used a water bottle of vodka to mix the patient's formula. This case adds to the paucity of literature of abnormal presentations of alcohol intoxication in an infant.

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations.

Alzheimer's disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. While in animal models of AD pathology, soluble tau aggregates have been shown to disrupt neuronal function, it is unclear whether the tau species present in CSF will modulate neural activity. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. The method involves incubation of acutely-isolated wild-type mouse hippocampal brain slices with small volumes of diluted human CSF, followed by a suite of electrophysiological recording methods to evaluate their effects on neuronal function, from single cells through to the network level. Comparison of the toxicity profiles of the same CSF samples, with and without immuno-depletion for tau, has enabled a pioneering demonstration that CSF-tau potently modulates neuronal function. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input-output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future.