Surface modification of extracellular vesicles with polyoxazolines to enhance their plasma stability and tumor accumulation.

Extracellular vesicles (EVs) are future promising therapeutics, but their instability in vivo after administration remains an important barrier to their further development. Many groups evaluated EV surface modification strategies to add a targeting group with the aim of controlling EV biodistribution. Conversely, fewer groups focused on their stabilization to obtain "stealth" allogenic EVs. Modulating their stabilization and biodistribution is an essential prerequisite for their development as nano-therapeutics. Here, we explored polyoxazolines with lipid anchors association to the EV membrane (POxylation as an alternative to PEGylation) to stabilize EVs in plasma and control their biodistribution, while preserving their native properties. We found that this modification maintained and seemed to potentiate the immunomodulatory properties of EVs derived from mesenchymal stem/stromal cells (MSC). Using a radiolabeling protocol to track EVs at a therapeutically relevant concentration in vivo, we demonstrated that POxylation is a promising option to stabilize EVs in plasma because it increased EV half-life by 6 fold at 6 h post-injection. Moreover, EV accumulation in tumors was higher after POxylation than after PEGylation.

HLA-E and NKG2A Mediate Resistance to M. bovis BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC. IFN-γ enhances HLA-E and PD-L1 expression in recurrent tumors, with an enrichment of intra-tumoral NKG2A-expressing NK and CD8 T cells. CXCL9 + macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7 + HLA-E HIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

Repurposing chemotherapy-induced peripheral neuropathy grading.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is perceived differently by patients and physicians, complicating its assessment. Current recommendations advocate combining clinical and patient-reported outcomes measures, but this approach can be challenging in patient care. This multicenter European study aims to bridge the gap between patients' perceptions and neurological impairments by aligning both perspectives to improve treatment decision-making. METHODS: Data were pooled from two prospective studies of subjects (n = 372) with established CIPN. Patient and physician views regarding CIPN were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Total Neuropathy Scale-clinical version (TNSc) items, and the disease-specific quality of life - Chemotherapy-Induced Peripheral Neuropathy questionnaire (QLQ-CIPN20) from the European Organization for Research and Treatment of Cancer (EORTC). To identify inherent neurotoxic severity patterns, we employed hierarchical cluster analysis optimized with k-means clustering and internally validated by discriminant functional analysis. RESULTS: Both NCI-CTCAE and TNSc demonstrated a significant difference in the distribution of severity grades in relation to QLQ-CIPN20 scores. However, a proportion of subjects with different neurotoxic severity grades exhibited overlapping QLQ-CIPN20 scores. We identified three distinct clusters classifying subjects as having severely impaired, intermediately impaired, and mildly impaired CIPN based on TNSc and QLQ-CIPN20 scores. No differences in demographics, cancer type distribution, or class of drug received were observed. CONCLUSIONS: Our results confirm the heterogeneity in CIPN perception between patients and physicians and identify three well-differentiated subgroups of patients delineated by degree of CIPN impairment based on scores derived from TNSc and QLQ-CIPN20. A more refined assessment of CIPN could potentially be achieved using the calculator tool derived from the cluster equations in this study. This tool, which facilitates individual patient classification, requires prospective validation.

Interosseus Membrane Reconstruction Following a Forearm Injury: A Case Report.

Background Essex-Lopresti injuries are complex, frequently missed forearm/elbow injuries consisting of a fracture of the radial head with disruption of both the distal radioulnar joint (DRUJ) and the interosseous membrane (IOM). Ideal management of these injuries remains controversial, especially in relation to the IOM, due in part to underdiagnosis of IOM injury and incomplete understanding of the IOM role. Methods A 43-year-old man sustained an open radial shaft fracture with associated radial head subluxation, coronoid base fracture, and DRUJ injury with ulnar head subluxation. He was taken for surgery, where elbow instability with near complete disruption of the IOM was observed. Persistent gross rotational instability was noted following radius fixation, so braided suture and button reconstruction of the central band of the IOM was performed. This restored rotational and longitudinal stability to the radiocapitellar joint and DRUJ. Over 1 year out from the index surgery, the patient's elbow and DRUJ have remained stable, and he is back working as a laborer. Results While little literature exists on outcomes of acute IOM reconstruction in these injuries, recent biomechanical studies have shown the importance of the central band on rotational elbow stability. Conclusion This case supports the importance of the central band of the IOM by demonstrating the impact of its repair on the longitudinal and rotational stability of the elbow and DRUJ. IOM repair has the potential to improve our treatment of this complicated injury by better restoring forearm stability and function of the elbow, which future studies could help further elucidate.

A shared decision-making intervention for individuals living with chronic obstructive pulmonary disease who are considering the menu of pulmonary rehabilitation treatment options; a feasibility study.

OBJECTIVES: Shared Decision Making (SDM) has potential to support Pulmonary Rehabilitation (PR) decision-making when patients are offered a menu of centre- and home-based options. This study sought to evaluate the feasibility and acceptability of a three-component PR SDM intervention for individuals with Chronic Obstructive Pulmonary Disease (COPD) and PR healthcare professionals. METHODS: Participants were recruited from Dec 2021-Sep 2022. Healthcare professionals attended decision coaching training and used the consultation prompt during consultations. Individuals received the Patient Decision Aid (PtDA) at PR referral. Outcomes included recruitment capability, data completeness, intervention fidelity, and acceptability. Questionnaires assessed patient activation and decisional conflict pre and post-PR. Consultations were assessed using Observer OPTION-5. Optional interviews/focus groups were conducted. RESULTS: 13% of individuals [n = 31, 32% female, mean (SD) age 71.19 (7.50), median (IQR) MRC dyspnoea 3.50 (1.75)] and 100 % of healthcare professionals (n = 9, 78% female) were recruited. 28 (90.32%) of individuals completed all questionnaires. SDM was present in all consultations [standardised scores were mean (SD) = 36.97 (21.40)]. Six healthcare professionals and five individuals were interviewed. All felt consultations using the PtDA minimised healthcare professionals' bias of centre-based PR, increased individuals' self-awareness of their health, prompted consideration of how to improve it, and increased involvement in decision-making. DISCUSSION: Results indicate the study processes and SDM intervention is feasible and acceptable and can be delivered with fidelity when integrated into the PR pathway.

The Contribution of Postprofessional Doctorates to the Career Development of Healthcare Workers: A Scoping Review.

INTRODUCTION: Doctorate education and implications for career trajectory for postprofessional healthcare workers like physician assistants/associates (PAs) remain under¬studied. PURPOSE: This scoping review identified findings from existing literature on the contribution of postprofessional doctorate (PPD) degrees to the career development of non-entry-level healthcare workers to inform the con¬temporary emergence of PA-specific doctorate programs in the United States. METHODS: The research followed the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. Eligible sources examined career advancement outcomes, curriculum, and terminal projects of PPD degree programs for postprofessional healthcare workers. Empirical studies, literature reviews, and commentaries were included. Multiple relevant databases, Google, and Google Scholar were searched. Citation chaining and hand searching of relevant journals were also completed. Screening and data extraction were conducted using Covidence. RESULTS: Among 1,605 sources identified, 24 met eligibility criteria. Most sources examined the Doctor of Nursing Practice and referenced clinical acumen, professional visibility, scholarly capability, leadership readiness, teaching preparation, and self-confidence. CONCLUSION: Findings about PA PPD degrees were limited. Sources exploring other professions demonstrated career development and educational outcomes, making assessment of results challenging. Future research should delineate critical competencies required for doctor¬ate-prepared PAs.

[Study on the impact of aging on the brain activity patterns in auditory speech comprehension dual-route regions].

Objective: To elucidate the patterns of neural activity alterations associated with auditory speech comprehension across the lifespan and the impact of varying listening environments on these dynamics. Methods: Functional near-infrared spectroscopy (fNIRS) was employed to measure the concentration of oxygenated hemoglobin in the brains of 93 adults aged from 20 to 70 with normal hearing. These participants were recruited from Beijing Tongren Hospital, affiliated with Capital Medical University, between March 2021 and February 2023. Brain activity was recorded as subjects passively listened to sentences in both silent and noise conditions with varying signal-to-noise ratios (SNR). The alterations in brain activity were analyzed to delineate the age-related trends under different auditory conditions. Statistical analysis was performed using SPSS 22.0 software. Results: The bilateral primary auditory cortex, superior temporal gyrus, and Wernicke's area, critical for sound signal discrimination and perception, exhibited enhanced activity post-stimulus presentation. Broca's area, pivotal for speech production, demonstrated an initial decrease in activity followed by an increment after stimulus onset. The ventral middle temporal gyrus and dorsal postcentral gyrus showed augmented activity in later time windows. Furthermore, it was observed that in quiet conditions and at low noise levels (SNR=10 dB), auditory cortical activity diminished with age. With increasing noise levels (SNR=5 dB), compensatory brain regions (right ventral middle temporal gyrus and dorsal postcentral gyrus) showed enhanced activity with advancing age. As noise intensity further escalated (SNR=0, SNR=-5 dB), not only did auditory cortical activity decline, but also the activity in regions associated with semantic processing and motor functions reduced with age. Conclusion: During auditory speech comprehension, dual-pathway brain regions exhibit distinct activity patterns. With heightened noise exposure, an increasing number of brain regions are influenced by aging, manifesting as a general decline in activity in most dual-pathway regions, alongside a selective augmentation in some compensatory regions on the right hemisphere.

A simply accessible organometallic system to gauge electronic properties of N-heterocyclic carbenes.

The intricate σ and π-bonding of N-heterocyclic carbenes (NHCs) to metals and the need to quantify their electronic properties to rationalize reactivity of complexes have resulted in the creation of numerous methodologies to understand the NHC-metal interaction which are, as we now show, flawed. Our search for a unified, easily accessible system to gauge these fundamental properties has resulted in the discovery of two systems that highlight the flaws present in existing systems and provide a more accurate measure of the NHC ligand electronic properties.

Interframe-tunable ultrafast differential-displacement holography.

We describe the details of a digital holographic microscopy diagnostic capable of quantifying both the topography and velocity of a km/s object with adjustable temporal sensitivity. This technique involves spatially multiplexing a double pulse reflected from a target with reference beams of precisely known temporal separation.

Structures and ammonia synthesis activity of hexagonal ruthenium iron nitride phases.

A series of ruthenium iron nitride phases with Ru:Fe ratios of ca. 1:3 were synthesized by ammonolysis. When the ammonolysis temperature was above 500°C, the obtained RuxFe3Ny materials had a ε-Fe3N (P6322) structure, while two similar phases were present when the ammonolysis was lower than 500°C. Powder neutron diffraction identified one phase as relating to the ε-Fe3N structure, while the other had a disordered NiAs-type (P63/mmc) structure. These ternary metal nitrides show ammonia synthesis activity at low temperature (200°C-300°C) and ambient pressure, which can be related to the loss of lattice nitrogen. Steady state catalytic performance at 400°C is associated with ruthenium-iron alloy. Additionally, density functional theory calculations were performed using an approximate model for the disordered hexagonal phase, revealing that this phase is more stable than a cubic anti-perovskite phase which has been previously investigated computationally, and corroborating the experimental findings of the present work.

Natural History, Phenotype Spectrum and Clinical Outcomes of Desmin (DES)-Associated Cardiomyopathy.

Background: Pathogenic/likely pathogenic (P/LP) desmin (DES) variants cause heterogeneous cardiomyopathy and/or skeletal myopathy phenotypes. Limited data suggest a high incidence of major adverse cardiac events (MACE), including cardiac conduction disease (CCD), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, LVAD/cardiac transplant, HF-related death), in patients with P/LP DES variants. However, pleiotropic presentation and small cohort sizes have limited clinical phenotype and outcome characterization. Objectives: We aimed to describe the natural history, phenotype spectrum, familial penetrance and outcomes in patients with P/LP DES variants through a systematic review and individual patient data meta-analysis using published reports. Methods: We searched Medline (PubMed) and Embase for studies that evaluated cardiac phenotypes in patients with P/LP DES variants. Cardiomyopathy diagnosis or occurrence of MACE were considered evidence of cardiac involvement/penetrance. Lifetime event-free survival from CCD, sustained VA, HF events, and composite MACE was assessed. Results: Out of 4,212 screened publications, 71 met the inclusion criteria. A total of 230 patients were included (52.6% male, 52.2% probands, median age: 31 years [22.0; 42.8] at first evaluation, median follow-up: 3 years [0; 11.0]). Overall, 124 (53.9%) patients were diagnosed with cardiomyopathy, predominantly dilated cardiomyopathy (14.8%), followed by restrictive cardiomyopathy (13.5%), whereas other forms were less common: arrhythmogenic cardiomyopathy (7.0%), hypertrophic cardiomyopathy (6.1%), arrhythmogenic right ventricular cardiomyopathy (5.2%), and other forms (7.4%). Overall, 132 (57.4%) patients developed MACE, with 96 [41.7%] having CCD, 36 [15.7%] sustained VA, and 43 [18.7%] HF events. Familial penetrance of cardiac disease was 63.6% among relatives with P/LP DES variants. Male sex was associated with increased risk of sustained VA (HR 2.28, p=0.02) and HF events (HR 2.45, p=0.008). Conclusions: DES cardiomyopathy exhibits heterogeneous phenotypes and distinct natural history, characterized by high familial penetrance and substantial MACE burden. Male patients face higher risk of sustained VA events.

Butyrate and propionate are microbial danger signals that activate the NLRP3 inflammasome in human macrophages upon TLR stimulation.

Short-chain fatty acids (SCFAs) are immunomodulatory compounds produced by the microbiome through dietary fiber fermentation. Although generally considered beneficial for gut health, patients suffering from inflammatory bowel disease (IBD) display poor tolerance to fiber-rich diets, suggesting that SCFAs may have contrary effects under inflammatory conditions. To investigate this, we examined the effect of SCFAs on human macrophages in the presence of Toll-like receptor (TLR) agonists. In contrast to anti-inflammatory effects under steady-state conditions, we found that butyrate and propionate activated the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in the presence of TLR agonists. Mechanistically, these SCFAs prevented transcription of FLICE-like inhibitory protein (cFLIP) and interleukin-10 (IL-10) through histone deacetylase (HDAC) inhibition, triggering caspase-8-dependent NLRP3 inflammasome activation. SCFA-driven NLRP3 activation was potassium efflux independent and did not result in cell death but rather triggered hyperactivation and IL-1ß release. Our findings demonstrate that butyrate and propionate are bacterially derived danger signals that regulate NLRP3 inflammasome activation through epigenetic modulation of the inflammatory response.

Context Matters: Internet Usage and Loneliness Among Middle-Aged and Older Adults During the COVID-19 Pandemic.

OBJECTIVES: Later life is often categorized by higher-than-average levels of loneliness, but individual differences are vast and not well understood. Emerging evidence indicates that broad-based contextual factors such as the COVID-19 pandemic - and the use of the internet throughout - are differentially associated with the experience of loneliness. We therefore target internet usage and loneliness among middle-aged and older adults during the pandemic and examine the moderating role of age, gender, and limiting illness therein. METHODS: We applied hierarchical regression models to data from the COVID-19 sub-study Wave 1 (June/July 2020) of the English Longitudinal Study of Ageing (N= 4,790; Mage= 70.2; SD= 9.0; range: 50-90; 43.5% male). RESULTS: Infrequent internet use was associated with less loneliness compared to very frequent users - an association that strengthened with age. Conversely, purpose of internet use was associated with more loneliness, with higher levels exhibited by those searching for health-related information - an effect stronger among those with a limiting illness. DISCUSSION: Findings imply that infrequent internet use may reduce loneliness, while health-related internet searches may increase loneliness among older adults with different physical capacities. Findings are contrary to pre-pandemic reports, underscoring the importance of broad-based contextual factors for understanding loneliness across adulthood and old age.

Optimal Hydrofluoric Acid Etching Duration and Impact of Silane/Adhesive on Profilometric Properties and Bonding to Lithium Disilicate Glass Ceramics.

OBJECTIVES: This study aimed to assess the surface roughness, surface free energy (SFE), and shear bond strength (SBS) on a lithium disilicate glass-ceramic surface following varying etching protocols (time variation) and application of silane either with or without adhesive material. METHODS AND MATERIALS: Lithium disilicate glassceramic (LDGC) computer-aided design and computer-aided manufacture (CAD/CAM) blocks were cut using a slow-speed cutting mechanism. CAD/CAM blocks were then evaluated for surface roughness, 6 groups (n=20); SFE,12 groups (n=5); and SBS, 10 groups (n=10). The cut CAD/CAM blocks were randomly allocated to 28 groups. Groups were based on the following: 30 or 90 seconds of etching with 9% hydrofluoric acid (HF); application or absence of silane coupling agent (Sil); and application or absence of adhesive (Adh).The control group (Cont) had untreated surfaces. Unetched surfaces were surveyed with only silane (Sil), only adhesive (Adh), or silane+adhesive (SilAdh). Further etched groups were HF30 with HF for 30 seconds, HF30-Sil, HF30-Adh, and HF30-SilAdh. Alternative 90-second etching times produced similar groups: HF90, HF90-Sil, HF90-Adh, and HF90-SilAdh. A digital profilometer was used to assess the surface roughness of specimens, and two readings were recorded. Sessile drop analysis was used to examine SFE specimens, and the OWRK model was modified to measure liquid surface tension. A universal testing machine (UltraTester, Ultradent Products, Inc, South Jordan, UT, USA) was utilized for the SBS test, with the crosshead speed set at 0.5 mm/min until failure. Representative treated specimens from each group were submitted to surface morphological evaluation and chemical analysis using scanning electron microscopy/energy dispersive x-ray spectroscopy (SEM/EDXS) (n=3). After data collection, evaluation using one- or two-way analysis of variance and the post-hoc Tukey test (α=5%) was conducted. RESULTS: A longer etching time of 90 seconds produced a rougher surface. After the 90-second etching process, SFE displayed the greatest values; nevertheless, the use of silane did not affect SFE. For every group examined, the application of silane followed by adhesive resulted in an increase in SBS and more stable bonding over time. SEM/EDXS showed that etching times did affect the amount of cerium on the surface and altered surface morphology. CONCLUSIONS: Higher and more consistent bond strengths have been observed with longer etching periods. Silane and adhesive application on the ceramic surface showed stronger and enhanced bond strength, specifically when longer etching times were employed.

Evaluation of Cerebrospinal Fluid α-Synuclein Seed Amplification Assay in Progressive Supranuclear Palsy and Corticobasal Syndrome.

BACKGROUND: Seed amplification assay (SAA) testing has been developed as a biomarker for the diagnosis of α-synuclein-related neurodegenerative disorders. OBJECTIVE: The objective of this study was to assess the rate of α-synuclein SAA positivity in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) and to analyze clinical and pathological features of SAA-positive and -negative cases. METHODS: A total of 96 cerebrospinal fluid samples from clinically diagnosed PSP (n = 59) and CBS (n = 37) cases were analyzed using α-synuclein SAA. RESULTS: Six of 59 (10.2%) PSP cases were α-synuclein SAA positive, including one case who was MSA-type positive. An exploratory analysis showed that PSP cases who were Parkinson's disease-type positive were older and had a shorter disease duration compared with SAA-negative cases. In contrast, 11 of 37 (29.7%) CBS cases were α-synuclein SAA positive, including two cases who were MSA-type positive. CONCLUSIONS: Our results suggest that α-synuclein seeds can be detected in PSP and CBS using a cerebrospinal fluid α-synuclein SAA, and in PSP this may impact on clinical course. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A comparison of smartphone and infrasound microphone data from a fuel air explosive and a high explosive.

For prompt detection of large (>1 kt) above-ground explosions, infrasound microphone networks and arrays are deployed at surveyed locations across the world. Denser regional and local networks are deployed for smaller explosions, however, they are limited in number and are often deployed temporarily for experiments. With the expanded interest in smaller yield explosions targeted at vulnerable areas such as population centers and key infrastructures, the need for more dense microphone networks has increased. An "attritable" (affordable, reusable, and replaceable) and flexible alternative can be provided by smartphone networks. Explosion signals from a fuel air explosive (thermobaric bomb) and a high explosive with trinitrotoluene equivalent yields of 6.35 and 3.63 kg, respectively, were captured on both an infrasound microphone and a network of smartphones. The resulting waveforms were compared in time, frequency, and time-frequency domains. The acoustic waveforms collected on smartphones produced a filtered explosion pulse due to the smartphone's diminishing frequency response at infrasound frequencies (<20 Hz) and was found difficult to be used with explosion characterization methods utilizing waveform features (peak overpressure, impulse, etc.). However, the similarities in time frequency representations and additional sensor inputs are promising for other explosion signal identification and analysis. As an example, a method utilizing the relative acoustic amplitudes for source localization using the smartphone sensor network is presented.

Electron Attachment to the Nucleobase Uracil in Diethylene Glycol: The Signature of a Doorway.

The cellular environment plays a significant role in low energy electron-mediated radiation damage to genetic materials. In this study, we have modeled the effect of the bulk medium on electron attachment to nucleobases in diethylene glycol (DEG) using uracil as a test case, in accordance with recent experimental work on the observation of dissociative quasi-free electron attachment to nucleoside via excited anion radical in solution (in DEG). Our EOM-CCSD-based quantum mechanical/molecular mechanical (QM/MM) simulations indicate that the electron scavenging by uracil in DEG is much slower than that observed in the aqueous medium due to its viscosity. This work also establishes that a doorway mechanism exists in uracil microsolvated and bulk solvated with DEG, with the dipole-bound state and solvent-bound state acting as doorway states, respectively.

Analysis of hippocampal synaptic function in a rodent model of early life stress.

Background: Early life stress (ELS) is an important risk factor in the aetiology of depression. Developmental glucocorticoid exposure impacts multiple brain regions with the hippocampus being particularly vulnerable. Hippocampal mediated behaviours are dependent upon the ability of neurones to undergo long-term potentiation (LTP), an N-methyl-D-aspartate receptor (NMDAR) mediated process. In this study we investigated the effect of ELS upon hippocampal NMDAR function. Methods: Hooded Long-Evans rat pups (n=82) were either undisturbed or maternally separated for 180 minutes per day (MS180) between post-natal day (PND) 1 and PND14. Model validation consisted of sucrose preference (n=18) and novelty supressed feeding (NSFT, n=34) tests alongside assessment of corticosterone (CORT) and paraventricular nucleus (PVN) cFos reactivity to stress and hippocampal neurogenesis (all n=18). AMPA/NMDA ratios (n=19), miniEPSC currents (n=19) and LTP (n=15) were assessed in whole-cell patch clamp experiments in CA1 pyramidal neurones. Results: MS180 animals showed increased feeding latency in the NSFT alongside increased overall CORT in the restraint stress experiment and increased PVN cFos expression in males but no changes in neurogenesis or sucrose preference. MS180 was associated with a lower AMPA/NMDA ratio with no change in miniEPSC amplitude or area. There was no difference in short- or long-term potentiation between MS180 and control animals nor were there any changes during the induction protocol. Conclusions: The MS180 model showed a behavioural phenotype consistent with previous work. MS180 animals showed increased NMDAR function with preliminary evidence suggesting that this was not concurrent with an increase in LTP.

Highly stressful early life events are the biggest risk factor for developing depression in adulthood. The hippocampus is a brain region that is highly susceptible to this stress and is crucial for coordinating learning and memory which underpins many aspects of cognitive function. Our study investigated if changes in the way that the neurons in the hippocampus communicate could provide explanations as to why early life stress predisposes to depression. We used an animal model of early life stress where rat pups are separated from their mother for three hours per day during their early life. Upon adulthood this resulted in the rats being slower to eat food in a new environment, a standard test of anxiety behaviour. We then used a technique called ex-vivo patch clamp electrophysiology to study how the individual neurons in their hippocampi and their connections functioned after early life stress. We measured the relative power of the signals from two key synaptic receptors essential for communication between neurons: AMPA and NMDA receptors. AMPA receptors are the key receptors enabling communication between neurons at synapses whereas NMDA receptors allow a neuron to become more sensitive to input signals and adapt synaptic strength. Animals with early life stress had more NMDA receptor function relative to AMPA function compared to control animals. We used a technique called miniEPSC recordings to rule out any change in AMPA receptor function in ELS animals meaning an effect specific to NMDA receptors. However, we found no changes to the ability for synapses to adapt their strength between groups. This work presents evidence for changes in hippocampal neurons and synapses caused by early life stress but further work is needed to understand how this relates to depression.