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In an early stage of Alzheimer's disease (AD), before the formation of amyloid plaques, neuronal network hyperactivity has been reported in both patients and animal models. This suggests an underlying disturbance of the balance between excitation and inhibition. Several studies have highlighted the role of somatic inhibition in early AD, while less is known about dendritic inhibition.

In this study we investigated how inhibitory synaptic currents are affected by elevated Aβ levels.

We performed whole-cell patch clamp recordings of CA1 pyramidal neurons in organotypic hippocampal slice cultures after treatment with Aβ-oligomers and in hippocampal brain slices from AppNL-F-G mice (APP-KI).

We found a reduction of spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in organotypic slices after 24 h Aβ treatment. sIPSCs with slow rise times were reduced, suggesting a specific loss of dendritic inhibitory inputs. As miniature IPSCs and synaptic density were unaffected, these results suggest a decrease in activity-dependent transmission after Aβ treatment. We observed a similar, although weaker, reduction in sIPSCs in CA1 pyramidal neurons from APP-KI mice compared to control. When separated by sex, the strongest reduction in sIPSC frequency was found in slices from male APP-KI mice. Consistent with hyperexcitability in pyramidal cells, dendritically targeting interneurons received slightly more excitatory input. GABAergic action potentials had faster kinetics in APP-KI slices.

Our results show that Aβ affects dendritic inhibition via impaired action potential driven release, possibly due to altered kinetics of GABAergic action potentials. Reduced dendritic inhibition may contribute to neuronal hyperactivity in early AD.

Our results show that Aβ affects dendritic inhibition via impaired action potential driven release, possibly due to altered kinetics of GABAergic action potentials. Reduced dendritic inhibition may contribute to neuronal hyperactivity in early AD.

Metagenomic data support an association between certain bacterial strains and Alzheimer's disease (AD), but their functional dynamics remain elusive.

To investigate the association between amyloid pathology, bacterial products such as lipopolysaccharide (LPS) and short chain fatty acids (SCFAs acetate, valerate, butyrate), inflammatory mediators, and markers of endothelial dysfunction in AD.

Eighty-nine older persons with cognitive performance from normal to dementia underwent florbetapir amyloid PET and blood collection. Brain amyloidosis was measured with standardized uptake value ratio versus cerebellum. Blood levels of LPS were measured by ELISA, SCFAs by mass spectrometry, cytokines by using real-time PCR, and biomarkers of endothelial dysfunction by flow cytometry. We investigated the association between the variables listed above with Spearman's rank test.

Amyloid SUVR uptake was positively associated with blood LPS (rho≥0.32, p≤0.006), acetate and valerate (rho≥0.45, p < 0.001), pro-inflammatory cytokines (rho≥0.25, p≤0.012), and biomarkers of endothelial dysfunction (rho≥0.25, p≤0.042). In contrast, it was negatively correlated with butyrate (rho≤-0.42, p≤0.020) and the anti-inflammatory cytokine IL10 (rho≤-0.26, p≤0.009). Endothelial dysfunction was positively associated with pro-inflammatory cytokines, acetate and valerate (rho≥0.25, p≤0.045) and negatively with butyrate and IL10 levels (rho≤-0.25, p≤0.038).

We report a novel association between gut microbiota-related products and systemic inflammation with brain amyloidosis via endothelial dysfunction, suggesting that SCFAs and LPS represent candidate pathophysiologic links between the gut microbiota and AD pathology.

We report a novel association between gut microbiota-related products and systemic inflammation with brain amyloidosis via endothelial dysfunction, suggesting that SCFAs and LPS represent candidate pathophysiologic links between the gut microbiota and AD pathology.

Elevated blood viscosity has been reported as a risk factor for cerebrovascular disease.

The relationship between blood viscosity and outcomes of mechanical thrombectomy (MT) for large artery occlusion (LAO) were investigated in the present study.

A total of 238 patients were enrolled and systolic blood viscosity (SBV) and diastolic blood viscosity (DBV) were measured using the scanning capillary tube viscometer. Receiver operating characteristic (ROC) analysis was performed to specify the association of viscosity with the first-pass reperfusion (FPR). Multivariable and regression analyses were performed to evaluate the relationship of viscosity with FPR and various variables.

Based on ROC analysis, the best DBV cutoff value was 10.55 (cP). In multivariable analysis, high DBV was associated with FPR failure (odds ratio 2.82, 95% confidence interval 1.64-4.22; p = 0.001). Increased DVB could be associated with elevated SBV, hematocrit level, and blood urea nitrogen/creatinine ratio (p = <0.001, 0.004, and 0.002, respectively).

Elevated DBV was associated with FPR failure. Patients with high DBV had longer thrombus length and required more stent passages than patients with low DBV.

Elevated DBV was associated with FPR failure. Patients with high DBV had longer thrombus length and required more stent passages than patients with low DBV.

COVID-19 is a systemic infection with a significant impact on coagulation which manifests in thromboembolism. There is an unknown relationship of which coagulation profile parameter at presentation has an association with poor outcome in COVID-19.

This meta-analysis aimed to determine the relationship between fibrinogen and FDP with poor outcome in COVID-19 patients.

A systematic search of all observational studies or trials involving adult patients with COVID-19 that had any data fibrinogen or FDP on admission was carried out using the PubMed, Science Direct, Scopus, ProQuest, and MedRxiv databases. We assessed the methodological quality assessment using the NIH Quality Assessment Tool. Paeoniflorin cost We performed random-effects inverse-variance weighting analysis using mean difference (MD).

A total of 17 studies (1,654 patients) were included in this meta-analysis. It revealed a higher mean of fibrinogen levels on admission in patients with severe case compared to those with non-severe case (MD = 0.69, [95% CI 0.44 to 0.

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