Synaptic alterations associated with disrupted sensory encoding in a mouse model of tauopathy.

Synapse loss is currently the best biological correlate of cognitive decline in Alzheimer's disease and other tauopathies. Synapses seem to be highly vulnerable to tau-mediated disruption in neurodegenerative tauopathies. However, it is unclear how and when this leads to alterations in function related to the progression of tauopathy and neurodegeneration. We used the well-characterized rTg4510 mouse model of tauopathy at 5-6 months and 7-8 months of age, respectively, to study the functional impact of cortical synapse loss. The earlier age was used as a model of prodromal tauopathy, with the later age corresponding to more advanced tau pathology and presumed progression of neurodegeneration. Analysis of synaptic protein expression in the somatosensory cortex showed significant reductions in synaptic proteins and NMDA and AMPA receptor subunit expression in rTg4510 mice. Surprisingly, in vitro whole-cell patch clamp electrophysiology from putative pyramidal neurons in layer 2/3 of the somatosensory cortex suggested no functional alterations in layer 4 to layer 2/3 synaptic transmission at 5-6 months. From these same neurons, however, there were alterations in dendritic structure, with increased branching proximal to the soma in rTg4510 neurons. Therefore, in vivo whole-cell patch clamp recordings were utilized to investigate synaptic function and integration in putative pyramidal neurons in layer 2/3 of the somatosensory cortex. These recordings revealed a significant increase in the peak response to synaptically driven sensory stimulation-evoked activity and a loss of temporal fidelity of the evoked signal to the input stimulus in rTg4510 neurons. Together, these data suggest that loss of synapses, changes in receptor expression and dendritic restructuring may lead to alterations in synaptic integration at a network level. Understanding these compensatory processes could identify targets to help delay symptomatic onset of dementia.

A comprehensive review and meta-analysis of suPAR as a predictor of acute kidney injury.

INTRODUCTION AND OBJECTIVE: The global impact of acute kidney injury (AKI) has not been thoroughly investigated. With the development of new techniques, soluble urokinase plasminogen activator receptor (suPAR) has become increasingly important in the diagnosis of AKI. Therefore, a systematic review and meta-analysis was carried out to evaluate the predictive value of suPAR for AKI. MATERIAL AND METHODS: The review and meta-analysis investigated the relationship between suPAR levels and acute kidney injury. Pubmed, Scopus, Cochrane Controlled Register of Trials, and Embase were searched for relevant studies from inception to 10 January 2023. Stata (Ver. 16 StataCorp, College Station, TX, USA) was used for all statistical analyses. A random effects model using the Mantel-Haenszel approach was employed, and odds ratios (OR) and standard mean differences (SMD) with 95% confidence intervals (CI) were calculated for binary and continuous outcomes, respectively. RESULTS: Nine studies reported suPAR levels among patients with and without AKI. Pooled analysis showed that suPAR levels in patients with and without AKI varied and amounted to 5.23 ± 4.07 vs. 3.23 ±0.67 ng/mL (SMD = 3.19; 95%CI: 2.73 to 3.65; p<0.001). The results from the sensitivity analysis did not alter the direction. CONCLUSIONS: This results show that increasing suPAR levels are associated with the occurrence of AKI. SuPAR might act as a novel biomarker for CI-AKI in clinical practice.

Prediction value of soluble urokinase plasminogen activator receptor (suPAR) in COVID-19 patients - a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVE: In COVID-19, the rapid prediction of the severity of a patient's condition using modern biomarkers can accelerate the implementation of appropriate therapy, and thus improve the patient's prognosis. MATERIAL AND METHODS: A meta-analysis was conducted of data available in the literature on the differences in baseline suPAR blood concentration between patients (1) who tested positive and negative for COVID-19, (2) who had severe and non-severe COVID-19, and (3) COVID-19 survivors and non-survivors. RESULTS: SuPAR levels in SARS-CoV-2 negative and positive patients varied and amounted to 3.61±1.59 ng/ml vs. 6.45±3.13 ng/ml, respectively (MD = -3.18; 95%CI: -4.71 to -1.66; p<0.001). suPAR levels among non-severe and severe COVID-19 patients were 7.06±2.64 ng/ml and 5.06±3.16 ng/ml (MD = 0.18; 95%CI: -2.48 to 2.83; p=0.90), respectively. Pooled analysis showed that suPAR levels between severe versus critical COVID-19 patients to be 5.59±1.54 ng/ml and 6.49±1.43 ng/ml, respectively (MD = -1.00; 95%CI: -1.31 to -0.70; p<0.001). The suPAR levels between ICU survivors versus non-survivors amounted to 5.82±2.33 ng/ml and 8.43±4.66 ng/ml (MD = -3.59; 95%CI: -6.19 to -1.00; p=0.007). In the case of in-hospital mortality, the mean suPAR level among survivors to hospital discharge was 5.63±1.27 ng/ml, compared to 7.85±2.61 ng/ml for patients who did not survive (MD = -3.58; 95%CI: -5.42 to -1.74; p<0.001). CONCLUSIONS: SuPAR levels are significantly elevated in severe COVID-19 illness and maybe useful in predicting mortality. Further studies are needed to determine cut-off points and clarify the association of suPAR levels with disease progression. This is of utmost importance given the ongoing pandemic and overburdened health care systems.

Prognostic Performance of Cystatin C in COVID-19: A Systematic Review and Meta-Analysis.

Cystatin C is a specific biomarker of kidney function. We perform this meta-analysis to determine the association of Cystatin C with the COVID-19 severity. In this systematic review and meta-analysis, we searched PubMed, EMBASE, Cochrane library, and Web of Science for studies published until 2nd September 2022 that reported associations between Cystatin C levels and COVID-19 severity. The analysis was performed using a random-effects model to calculate pooled standard mean difference (SMD). Twenty-five studies were included in the meta-analysis. Pooled analysis showed statistically significant differences of Cystatin C levels among survive vs. decreased patients (0.998 ± 0.225 vs. 1.328 ± 0.475 mg/dL, respectively; SMD = -2.14; 95%CI: -3.28 to -1.01; p < 0.001). Cystatin C levels in COVID-19 severe vs. non-severe groups varied and amounted to 1.485 ± 1.191 vs. 1.014 ± 0.601 mg/dL, respectively (SMD = 1.81; 95%CI: 1.29 to 2.32; p < 0.001). Additionally, pooled analysis showed that Cystatin C levels in patients with acute kidney injury (AKI) was 1.562 ± 0.885 mg/dL, compared to 0.811 ± 0.108 mg/dL for patients without AKI (SMD = 4.56; 95%CI: 0.27 to 8.85; p = 0.04). Summing up, Cystatin C is a potentially very good marker to be used in the context of COVID-19 disease due to the prognosis of patients' serious condition, risk of AKI and mortality. In addition, Cystatin C could be used as a marker of renal complications in COVID-19 other than AKI due to the need to monitor patients even longer after leaving the hospital.

Influence of Noise in Computer-Vision-Based Measurements on Parameter Identification in Structural Dynamics.

Nowadays, consumer electronics offer computer-vision-based (CV) measurements of dynamic displacements with some trade-offs between sampling frequency, resolution and low cost of the device. This study considers a consumer-grade smartphone camera based on complementary metal-oxide semiconductor (CMOS) technology and investigates the influence of its hardware limitations on the estimation of dynamic displacements, modal parameters and stiffness parameters of bolted connections in a laboratory structure. An algorithm that maximizes the zero-normalized cross-correlation function is employed to extract the dynamic displacements. The modal parameters are identified with the stochastic subspace identification method. The stiffness parameters are identified using a model-updating technique based on modal sensitivities. The results are compared with the corresponding data obtained with accelerometers and a laser distance sensor. The CV measurement allows lower-order vibration modes to be identified with a systematic (bias) error that is nearly proportional to the vibration frequency: from 2% for the first mode (9.4 Hz) to 10% for the third mode (71.4 Hz). However, the measurement errors introduced by the smartphone camera have a significantly lower influence on the values of the identified stiffness parameters than the numbers of modes and parameters taken into account. This is due to the bias-variance trade-off. The results show that consumer-grade electronics can be used as a low-cost and easy-to-use measurement tool if lower-order modes are required.

Trajectory Identification for Moving Loads by Multicriterial Optimization.

Moving load is a fundamental loading pattern for many civil engineering structures and machines. This paper proposes and experimentally verifies an approach for indirect identification of 2D trajectories of moving loads. In line with the "structure as a sensor" paradigm, the identification is performed indirectly, based on the measured mechanical response of the structure. However, trivial solutions that directly fit the mechanical response tend to be erratic due to measurement and modeling errors. To achieve physically meaningful results, these solutions need to be numerically regularized with respect to expected geometric characteristics of trajectories. This paper proposes a respective multicriterial optimization framework based on two groups of criteria of a very different nature: mechanical (to fit the measured response of the structure) and geometric (to account for the geometric regularity of typical trajectories). The state-of-the-art multiobjective genetic algorithm NSGA-II is used to find the Pareto front. The proposed approach is verified experimentally using a lab setup consisting of a plate instrumented with strain gauges and a line-follower robot. Three trajectories are tested, and in each case the determined Pareto front is found to properly balance between the mechanical response fit and the geometric regularity of the trajectory.

Bridge Damage Identification Using Vehicle Bump Based on Additional Virtual Masses.

Structural damage identification plays an important role in providing effective evidence for the health monitoring of bridges in service. Due to the limitations of measurement points and lack of valid structural response data, the accurate identification of structural damage, especially for large-scale structures, remains difficult. Based on additional virtual mass, this paper presents a damage identification method for bridges using a vehicle bump as the excitation. First, general equations of virtual modifications, including virtual mass, stiffness, and damping, are derived. A theoretical method for damage identification, which is based on additional virtual mass, is formulated. The vehicle bump is analyzed, and the bump-induced excitation is estimated via a detailed analysis in four periods: separation, free-fall, contact, and coupled vibrations. The precise estimation of bump-induced excitation is then applied to a bridge. This allows the additional virtual mass method to be used, which requires knowledge of the excitations and acceleration responses in order to construct the frequency responses of a virtual structure with an additional virtual mass. Via this method, a virtual mass with substantially more weight than a typical vehicle is added to the bridge, which provides a sufficient amount of modal information for accurate damage identification while avoiding the bridge overloading problem. A numerical example of a two-span continuous beam is used to verify the proposed method, where the damage can be identified even with 15% Gaussian random noise pollution using a 1-degree of freedom (DOF) car model and 4-DOF model.

Resistant hypertension: Renal denervation or pharmacovigilance? Insights from a renal denervation screening program.

BACKGROUND: With emerging new therapeutic concepts including renal denervation (RDN), there is a renewed interest in resistant hypertension (ResH). Among patients suspected of having ResH, a definitive diagnosis needs to be established. OBJECTIVES: This study presents observations from a standardized single-center screening program for RDN candidates, including medical therapy modification and reassessment. MATERIAL AND METHODS: All patients referred to our center for RDN underwent a standardized screening protocol. Candidates were recruited from among patients receiving no less than 3 antihypertensive drugs, including diuretics with office blood pressure (BP) >140/90 mm Hg. The assessment included 2 measurements of BP and ambulatory BP monitoring (ABPM). If needed, pharmacotherapy was intensified and the diagnosis of ResH was reconfirmed after 6 weeks. If ResH was persistent, patients were hospitalized with repeated ABPM on day 4. Further, renal CT-angio was performed and a multidisciplinary team discussed the patients' suitability for RDN. RESULTS: A total of 87 patients with a ResH diagnosis were referred for RDN. Mean office BP was 159/92 (±7.0/6.5) mm Hg and mean ABPM was 154/90 (±9.0/4.8) mm Hg. The initial medication included angiotensin convertase inhibitors (ACE-I, 78%), angiotensin receptor blockers (12%), ß-blockers (85%), calcium channel blockers (36%), and diuretics (93%). During the 18 months of the RDN program, 5 patients underwent RDN and 2 further had ineligible renal anatomy. A new diagnosis of secondary hypertension was made in 21 patients. However, in 59 patients, BP control was achieved after optimization of medical therapy, with a mean ABPM of 124/74 mm Hg. The final treatment included ACE-I (100%), ß-blockers (92%), indapamide (94%), amlodipine (72%), and spironolactone (61%). Medication in most of these patients (88%) included single-pill triple combination (52.5%) or double combination (35.6%). CONCLUSIONS: Patients with elevated BP screened for RDN require a rigorous diagnostic workup. Up to 2/3 of patients can be managed with strict pharmacotherapy compliance and pharmaceutical intensification, including single-pill combinations and improved drug compliance. Hasty use of RDN may be a result of poor drug optimization and/or compliance. It does remain a viable treatment option in thoroughly vetted ResH patients.

Optimal Placement of Virtual Masses for Structural Damage Identification.

Adding virtual masses to a structure is an efficient way to generate a large number of natural frequencies for damage identification. The influence of a virtual mass can be expressed by Virtual Distortion Method (VDM) using the response measured by a sensor at the involved point. The proper placement of the virtual masses can improve the accuracy of damage identification, therefore the problem of their optimal placement is studied in this paper. Firstly, the damage sensitivity matrix of the structure with added virtual masses is built. The Volumetric Maximum Criterion of the sensitivity matrix is established to ensure the mutual independence of measurement points for the optimization of mass placement. Secondly, a method of sensitivity analysis and error analysis is proposed to determine the values of the virtual masses, and then an improved version of the Particle Swarm Optimization (PSO) algorithm is proposed for placement optimization of the virtual masses. Finally, the optimized placement is used to identify the damage of structures. The effectiveness of the proposed method is verified by a numerical simulation of a simply supported beam structure and a truss structure.

Experimental Study for Damage Identification of Storage Tanks by Adding Virtual Masses.

This research proposes a damage identification approach for storage tanks that is based on adding virtual masses. First, the frequency response function of a structure with additional virtual masses is deduced based on the Virtual Distortion Method (VDM). Subsequently, a Finite Element (FE) model of a storage tank is established to verify the proposed method; the relation between the added virtual masses and the sensitivity of the virtual structure is analyzed to determine the optimal mass and the corresponding frequency with the highest sensitivity with respect to potential damages. Thereupon, the damage can be localized and quantified by comparing the damage factors of substructures. Finally, an experimental study is conducted on a storage tank. The results confirm that the proposed method is feasible and practical, and that it can be applied for damage identification of storage tanks.

Outcomes of percutaneous coronary intervention in patients after previous coronary artery bypass surgery.

BACKGROUND: Patients after previous coronary artery bypass grafting (CABG) often require repeat percutaneous revascularisation due to poor patency rates of saphenous vein grafts (SVG) and higher risk of re-CABG. Few data are available to evaluate different percutaneous revascularisation strategies in patients after previous CABG. AIM: To evaluate outcomes of percutaneous coronary intervention (PCI) in patients after previous CABG, including the effect of treatment on the quality of life and symptoms, and secondly to assess the relation between angiographic factors and treatment outcomes METHODS: This was a prospective observational study which included 78 patients after previous CABG. Following coronary angiography, the patients were assigned to one of three groups: group A (n = 20), PCI of a SVG (PCI SVG); group B (n = 29), PCI of a native coronary artery (PCI NA); group C (n = 29), control group that received medical treatment (MT) only. Duration of follow-up was 12 months. RESULTS: Compared to MT patients, patients treated with PCI had significantly higher Canadian Cardiovascular Society (CCS) class (2.75 vs. 2.41, p = 0.03) and more frequently had coronary angiography performed due to unstable angina (57% vs. 31%, p = 0.04). Patients in the PCI SVG group had significantly older SVG conduits compared to the PCI NA group (13.4 years vs. 8.2 years, p = 0.005). At 12 months of follow-up, we found a significant improvement in the EQ-5D index of the quality of life, and a significant reduction in CCS class in the PCI SVG group (0.66 vs. 0.7, p = 0.0003, and 2.75 vs. 1.9, p < 0.001, respectively) and in the PCI NA group (0.65 vs. 0.72, p < 0.001, and 2.75 vs. 2.17, p < 0.001, respectively), but no improvement in the MT group. Treatment outcomes did not differ significantly between the three groups (combined endpoint rate 20% vs. 13% vs. 27.5%, p = 0.37). In multivariate analysis, SVG age > 11 years was identified as a significant predictor of poor outcomes in patients treated with PCI after previous CABG. CONCLUSIONS: PCI in patients after previous CABG does not improve prognosis but significantly improves the quality of life and reduces symptom severity.

Ultrasound evaluation of forearm arteries in patients undergoing percutaneous coronary intervention via radial artery access: results of one-year follow-up.

BACKGROUND: A proven advantage of radial over femoral arterial access has led to an increase in the number of interventions performed via radial artery access in patients with acute coronary syndromes. Both assessment of the pulse volume and the Allen's test are subjective and subject to investigator bias. An ultrasound examination of the forearm arteries provides important information about the anatomy of the forearm vessels, and indirectly also about the efficiency of collateral blood supply to the hand. It also enables determination of the relevant vessel diameter before the planned intervention, and may be used to assess local complications. AIM: To assess the morphology of forearm blood vessels and measure the diameter of both radial and ulnar arteries at the cannulation site using ultrasound imaging. We also aimed to identify potential vascular anomalies and local complications associated with radial artery puncture. METHODS: The study included 109 patients with cardiologic indications for coronary angiography or coronary angioplasty. An ultrasound evaluation of forearm arteries was performed prior to the intervention, and the vascular anatomy was later verified by angiography during the procedure. Ultrasound measurements of the vessel diameter were also performed and local complications of the cannulation were assessed. Measurements were performed immediately after the procedure and at 30 days and 12 months. RESULTS: Fifty-nine right and 50 left forearm arteries were evaluated. Women were 29% of the study population. The mean patient age was 59.2 ± 7.9 years. The mean diameter of the right radial artery was 2.17 ± 0.54 mm, and the mean diameter of the left radial artery was 2.25 ± 0.43 mm. The measurements revealed gender-related differences in forearm artery diameter (p = 0.003). Vascular anomalies of the radial artery were identified by ultrasound examination in 10% of subjects. A significant dilatation of the cannulated blood vessel was observed which lasted up to 12 months. An occlusion of the cannulated artery was demonstrated in 6.4% of patients. CONCLUSIONS: Ultrasound imaging is a reliable method to evaluate the diameter of forearm arteries and track their course in patients undergoing invasive cardiovascular procedures via radial artery access. The diameter of the radial artery by ultrasound evaluation is larger compared to that of the ulnar artery. The diameter of forearm arteries in women is smaller compared to men. A dilatation of the radial artery which may last up to 12 months develops following its percutaneous cannulation. Ultrasound imaging allows detection and monitoring of local complications such as radial artery occlusion. An unfavourable ratio of blood vessel diameter to the size of the used introducer sheath is a predictor of radial artery occlusion. Ultrasound imaging enables reliable evaluation of vascular anomalies involving the radial artery, especially within the distal forearm.

Enhanced responsivity with skew ray excitation of reflection- and transmission-type refractometric sensors.

The responsivity of optical fibers to refractive index can be enhanced using high-order skew rays compared with using meridional rays. Skew rays can have a much higher number of reflections with increased interaction length along the core-cladding interface, which gives rise to stronger interactions with the external medium. Reflection/transmission-type refractometric sensors based on twin-coupled-core and multimode fibers showed one/two orders of magnitude increase in responsivity with skew ray excitation. The responsivity and sensitivity for the two types are ~2000%/RIU, ~1400%/RIU, and 4.9×10⁻5 RIU, 7.0×10⁻5 RIU, respectively.

[Should the patient with myocardial bridge be advised not to performe extreme sport effort? Case of a patient with troponin I elevation after exercise]. / Przypadek chorego z odwyzszonym stezeniem troponiny I po wysilku.

Elevated levels of cardiac troponins are an established method of diagnosis of heart muscle necrosis. A case of a long distance amateur-marathon runner, who showed significant elevation of plasma troponin I after extreme physical effort is reported. The diagnostic examinations did not reveal atherosclerosis burden, but myocardial bridging of coronary artery. The authors describe the significance of the pathology in the view of extreme sport effort performed by the described patient.