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Zsombor Tóth-Vajna,1 Gergely Tóth-Vajna,2 Zsuzsanna Gombos,1 Brigitta Szilágyi,3 Zoltán Járai,4,5 Márton Berczeli,1 Péter Sótonyi11Heart and Vascular Center, Department of Vascular Surgery, Semmelweis University, Budapest, Hungary; 21st Department of Pediatrics, Semmelweis University, Budapest, Hungary; 3Department of Geometry, Institute of Mathematics, Budapest University of Technology and Economics, Budapest, Hungary; 4Department of Cardiology, St. Emeric University Teaching Hospital, Budapest, Hungary; 5Heart and Vascular Center, Department of Vascular Surgery, Department of Angiology, Semmelweis University, Budapest, HungaryCorrespondence: Márton BerczeliHeart and Vascular Center, Department of Vascular Surgery, Semmelweis University, 68 Városmajor Street, Budapest 1122, HungaryTel +36 20 666 3354Email marton.berczeli@gmail.comBackground and purpose: The screening tool for diagnosing lower extremity arterial disease is the assessment of the ankle-brachial index (ABI), which is widely used in general practice. However, resting ABI can easily produce a false negative result. In light of this, our goal was to determine the proportion of definitive diagnoses (peripheral arterial disease [PAD] confirmed or refuted) among patients screened in general practice, and the rate of cases in which the need for further specialized examination is necessary, with special attention to groups having non-compressible arteries and ABI negative symptomatic status. The aim of our work is to improve the efficiency of primary health care screening in PAD and reduce the extremely high domestic amputation ratio.Patients and methods: Eight hundred and sixteen patients were screened. We used the Edinburgh Questionnaire and recorded medical histories, major risk factors, current complaints, and medication. Physical examinations were performed, including ABI testing.Results: Thirty-three percent complained about lower extremity claudication; 23% had abnormal ABI values; 13% of the patients within the normal ABI range had complaints of dysbasia; and 12% were in the non-compressible artery group. The ABI-negative symptomatic group’s risk factor profile showed a close similarity to the clear PAD-positive and non-compressible artery groups.Conclusion: The percentage of PAD could be higher than the number of patients diagnosed by ABI screening. Nearly a quarter of the population fell into the non-compressible artery and ABI-negative symptomatic groups, together defined as the “murky zone”. When screening purposely for PAD, these patients deserve special attention due to the insufficient selectivity and sensitivity of measurements. If there is high clinical suspicion of PAD in spite of normal ABI values, further assessment may be considered.Keywords: peripheral arterial disease, ankle-brachial index, diabetes, screening method, ABI-negative symptomatic, non-compressible artery

Previous research confirmed gut dysbiosis and translocation of selected intestinal bacteria into the vessel wall in abdominal aortic aneurysm patients. We studied the stool, blood, thrombus and aneurysm microbiomes of 21 abdominal aortic aneurysm patients using 16S rRNA sequencing. Our goals were to determine: 1. whether the microbiome characteristic of an aneurysm differs from that of a healthy vessel, 2. whether bacteria detectable in the aneurysm are translocated from the gut through the bloodstream, 3. whether the enzymatic activity of the aneurysm microbiome can contribute to the destruction of the vessel wall. The abundance of Acinetobacter, Burkholderia, Escherichia, and Sphingobium in the aneurysm samples was significantly higher than that in the microbiome of healthy vessels, but only a part of these bacteria can come from the intestine via the blood. Environmental bacteria due to the oral cavity or skin penetration route, such as Acinetobacter, Sphingobium, Enhydrobacter, and Aquabacterium, were present in the thrombus and aneurysm with a significantly higher abundance compared to the blood. Among the enzymes of the microbiome associated with the healthy vessel wall, Iron-chelate-transporting ATPase and Polar-amino-acid-transporting ATPase have protective effects. In addition, bacterial Peptidylprolyl isomerase activity found in the aneurysm has an aggravating effect on the formation of aneurysm.

Background: We conducted an in vitro comparison of the snare loop reinforcement against a closed-loop reinforcement (Hungaroring) for physician-modified endograft (PMEG) fenestrations regarding preparation time and stability during flaring balloon dilatation. Materials and methods: The time to complete a PMEG fenestration with reinforcement was measured and compared between the Hungaroring and snare loop groups. The number of stitches was counted. Each fenestration was dilated using a 10 mm high-pressure, non-compliant balloon up to 21 atm in pressure, and fluoroscopic images were taken. The presence of indentation on the oversized balloon at the level of the reinforcement was evaluated at each fenestration. Results: Five fenestrations were created in each group (n = 5) for a total of ten pieces. The completion time in the snare loop group was 1070 s (IQR:1010–1090) compared to 760 s (IQR:685–784) in the Hungaroring group (p = 0.008). Faster completion time was achieved by faster stitching (23.2 s/stitch (IQR 22.8–27.3) for the snare loop group and 17.3 s/stitch (IQR 17.3–20.1) for the Hungaroring group (p = 0.016). None of the fluoroscopic images of the snare loop reinforcement showed an indentation on the balloon during the overexpansion; on the contrary, the Hungaroring showed indentation in every case, even at 21 atm. Conclusion: Fenestrations reinforced with Hungaroring can be completed significantly faster. Furthermore, the Hungaroring resists over-dilation even at high pressures, while snare loop reinforcements dilate at nominal pressure.

This review aims to explore advancements in perioperative ischemic stroke risk estimation for asymptomatic patients with significant carotid artery stenosis, focusing on Circle of Willis (CoW) morphology based on the CTA or MR diagnostic imaging in the current preoperative diagnostic algorithm. Functional transcranial Doppler (fTCD), near-infrared spectroscopy (NIRS), and optical coherence tomography angiography (OCTA) are discussed in the context of evaluating cerebrovascular reserve capacity and collateral vascular systems, particularly the CoW. These non-invasive diagnostic tools provide additional valuable insights into the cerebral perfusion status. They support biomedical modeling as the gold standard for the prediction of the potential impact of carotid artery stenosis on the hemodynamic changes of cerebral perfusion. Intraoperative risk assessment strategies, including selective shunting, are explored with a focus on CoW variations and their implications for perioperative ischemic stroke and cognitive function decline. By synthesizing these insights, this review underscores the potential of non-invasive diagnostic methods to support clinical decision making and improve asymptomatic patient outcomes by reducing the risk of perioperative ischemic neurological events and preventing further cognitive decline.

Carotid artery stenosis (CAS) affects approximately 5–7.5% of older adults and is recognized as a significant risk factor for vascular cognitive impairment (VCI). The impact of CAS on cerebral blood flow (CBF) within the ipsilateral hemisphere relies on the adaptive capabilities of the cerebral microcirculation. In this study, we aimed to test the hypothesis that the impaired availability of nitric oxide (NO) compromises CBF homeostasis after unilateral carotid artery occlusion (CAO). To investigate this, three mouse models exhibiting compromised production of NO were tested: NOS1 knockout, NOS1/3 double knockout, and mice treated with the NO synthesis inhibitor L-NAME. Regional CBF changes following CAO were evaluated using laser-speckle contrast imaging (LSCI). Our findings demonstrated that NOS1 knockout, NOS1/3 double knockout, and L-NAME-treated mice exhibited impaired CBF adaptation to CAO. Furthermore, genetic deficiency of one or two NO synthase isoforms increased the tortuosity of pial collaterals connecting the frontoparietal and temporal regions. In conclusion, our study highlights the significant contribution of NO production to the functional adaptation of cerebrocortical microcirculation to unilateral CAO. We propose that impaired bioavailability of NO contributes to the impaired CBF homeostasis by altering inter- and intrahemispheric blood flow redistribution after unilateral disruption of carotid artery flow.

BackgroundThe cerebral and retinal circulation systems are developmentally, anatomically, and physiologically interconnected. Thus, we hypothesized that hypoperfusion due to atherosclerotic stenosis of the internal carotid artery (ICA) can result in disturbances of both cerebral and retinal microcirculations. We aimed to characterize parameters indicating cerebrovascular reactivity (CVR) and retinal microvascular density in patients with ICA stenosis, and assess if there is correlation between them.MethodsIn this cross-sectional study the middle cerebral artery (MCA) blood flow velocity was measured by transcranial Doppler (TCD) and, simultaneously, continuous non-invasive arterial blood pressure measurement was performed on the radial artery by applanation tonometry. CVR was assessed based on the response to the common carotid artery compression (CCC) test. The transient hyperemic response ratio (THRR) and cerebral arterial resistance transient hyperemic response ratio (CAR-THRR) were calculated. Optical coherence tomography angiography (OCTA) was used to determine vessel density (VD) on the papilla whole image for all (VDP-WIall) and for small vessels (VDP-WIsmall). The same was done in the peripapillary region: all (VDPPall), and small (VDPPsmall) vessels. The VD of superficial (VDMspf) and deep (VDMdeep) macula was also determined. Significance was accepted when pResultsTwenty-four ICA stenotic patients were evaluated. Both CVR and retinal VD were characterized. There was a significant, negative correlation between CAR-THRR (median = -0.40) and VDPPsmall vessels (median = 52%), as well as between VDPPall vessels (median = 58%), and similar correlation between CAR-THRR and VDP-WIsmall (median = 49.5%) and between VDP-WIall (median = 55%).ConclusionThe significant correlation between impaired cerebrovascular reactivity and retinal vessel density in patients with ICA stenosis suggests a common mechanism of action. We propose that the combined use of these diagnostic tools (TCD and OCTA) helps to better identify patients with increased ischemic or other cerebrovascular risks.

The Circle of Willis (CoW) is the main collateral system, and its morphological variants are more common in patients who have severe carotid artery stenosis. Earlier data suggest that optical coherence tomography angiography (OCTA) may help to assess the changes in cerebral vascular perfusion by imaging the retinal blood flow. In this single-center prospective clinical study, patients scheduled for carotid endarterectomy (CEA) underwent preoperative computed tomography angiography (CTA) of the extra- and intracranial cerebral circulation. OCTA imaging was performed one week before surgery and postoperatively one month later. The patients were divided into two subgroups based on CTA evaluation of CoW: compromised CoW or non-compromised CoW (containing hypoplastic and normal segments). The effect of the patient’s age, OCTA scan quality (SQ), CoW morphology, laterality, and surgery on superficial capillary vessel density (VD) in the macula were assessed in multivariable regression models using linear mixed models. We found that VD significantly decreased with aging (−0.12%; 95%CI: −0.07–−0.15; p < 0.001) and was significantly higher in patients with non-compromised CoW morphology (by 0.87% 95%CI (0.26–1.50); p = 0.005). After CEA, retinal blood flow significantly improved by 0.71% (95%CI: 0.18–1.25; p = 0.01). These results suggest that in the case of carotid artery occlusion, patients with non-compromised CoW have more preserved ocular blood flow than subjects with compromised CoW due to remodeling of the intra-orbital blood flow. Measuring the retinal blood flow might be used as a relevant and sensitive indicator of collateral cerebrovascular circulation.

Abstract Our aim was to investigate whether the previously observed higher contrast-to-noise ratio (CNR) and better image quality of Digital Variance Angiography (DVA) - compared to Digital Subtraction Angiography (DSA) - can be used to reduce radiation exposure in lower limb X-ray angiography. This prospective study enrolled 30 peripheral artery disease patients (mean ± SD age 70 ± 8 years) undergoing diagnostic angiography. In all patients, both normal (1.2 µGy/frame; 100%) and low-dose (0.36 µGy/frame; 30%) protocols were used for the acquisition of images in three anatomical regions (abdominal, femoral, crural). The CNR of DSA and DVA images were calculated, and the visual quality was evaluated by seven specialists using a 5-grade Likert scale. For investigating non-inferiority, the difference of low-dose DVA and normal dose DSA scores (DVA30-DSA100) was analyzed. DVA produced two- to three-fold CNR and significantly higher visual score than DSA. DVA30 proved to be superior to DSA100 in the crural region (difference 0.25 ± 0.07, p

Discovery of human microbiota is fundamentally changing our perceptions of certain diseases and their treatments. However little is known about the human blood vessel microbiota, it may have important effects on vascular pathological lesions and vascular homograft failure. In our prospective survey study fourteen femoral arteries, harvested from donors in multi-organ donations, were examined using the V3-V4 region 16S rRNA sequencing method. The most abundant phyla in the human vascular microbiota were Proteobacteria, Firmicutes and Actinobacteria. At the genus level, the most abundant taxa were Staphylococcus, Corynebacterium, Pseudomonas, Bacillus, Acinetobacter and Propionibacterium. Of the bacterial taxa that have an indirect effect on the development of atherosclerosis, we found Porphyromonas gingivalis, Prevotella nigrescens and Enterobacteriaceae spp. with different abundances in our samples. Of the bacteria that are more common in the intestinal flora of healthy than of atherosclerosis patients, Roseburia and Ruminococcus occurred in the majority of samples. The human arterial wall has a unique microbiota that is significantly different in composition from that of other areas of the body. Our present study provides a basis for ensuing research that investigates the direct role of the microbiota in vascular wall abnormalities and the success of vascular allograft transplantations.

(1) Study purpose: The aim of our prospective single-center, matched case–control study was to compare the number and volume of acute ischemic brain lesions following carotid endarterectomy (CEA) versus carotid artery stenting (CAS) using a propensity-matched design. (2) Methods: Carotid bifurcation plaques were analyzed by using VascuCAP software on CT angiography (CTA) images. The number and volume of acute and chronic ischemic brain lesions were assessed on MRI scans taken 12–48 h after the procedures. Propensity score-based matching was performed at a 1:1 ratio to compare the ischemic lesions on postinterventional MR. (3) Results: A total of 107 patients (CAS, N = 33; CEA, N = 74) were included in the study. There were significant differences in smoking (p = 0.003), total calcification plaque volume (p = 0.004), and lengths of the lesion (p = 0.045) between the CAS and CEA groups. Propensity score matching resulted in 21 matched pairs of patients. Acute ischemic brain lesions were detected in ten patients (47.6%) of the matched CAS group and in three patients (14.2%) in the matched CEA group (p = 0.02). The volume of acute ischemic brain lesions was significantly larger (p = 0.04) in the CAS group than in the CEA group. New ischemic brain lesions were not associated with neurological symptoms in either group. (4) Conclusions: Procedure-related new acute ischemic brain lesions occurred significantly more frequently in the propensity-matched CAS group.

Background: digital variance angiography (DVA) provides higher image quality than digital subtraction angiography (DSA). This study investigates whether the quality reserve of DVA allows for radiation dose reduction during lower limb angiography (LLA), and compares the performance of two DVA algorithms. Methods: this prospective block-randomized controlled study enrolled 114 peripheral arterial disease patients undergoing LLA into normal dose (ND, 1.2 µGy/frame, n = 57) or low-dose (LD, 0.36 µGy/frame, n = 57) groups. DSA images were generated in both groups, DVA1 and DVA2 images were generated in the LD group. Total and DSA-related radiation dose area product (DAP) were analyzed. Image quality was assessed on a 5-grade Likert scale by six readers. Results: the total and DSA-related DAP were reduced by 38% and 61% in the LD group. The overall visual evaluation scores (median (IQR)) of LD-DSA (3.50 (1.17)) were significantly lower than the ND-DSA scores (3.83 (1.00), p < 0.001). There was no difference between ND-DSA and LD-DVA1 (3.83 (1.17)), but the LD-DVA2 scores were significantly higher (4.00 (0.83), p < 0.01). The difference between LD-DVA2 and LD-DVA1 was also significant (p < 0.001). Conclusions: DVA significantly reduced the total and DSA-related radiation dose in LLA, without affecting the image quality. LD-DVA2 images outperformed LD-DVA1, therefore DVA2 might be especially beneficial in lower limb interventions.

Abstract Dendritic spines are the primary sites of excitatory transmission in the mammalian brain. Spines of cerebellar Purkinje Cells (PCs) are plastic, but they differ from forebrain spines in a number of important respects, and the mechanisms of spine plasticity differ between forebrain and cerebellum. Our previous studies indicate that in hippocampal spines cortactin—a protein that stabilizes actin branch points—resides in the spine core, avoiding the spine shell. To see whether the distribution of cortactin differs in PC spines, we examined its subcellular organization using quantitative preembedding immunoelectron microscopy. We found that cortactin was enriched in the spine shell, associated with the non-synaptic membrane, and was also situated within the postsynaptic density (PSD). This previously unrecognized distribution of cortactin within PC spines may underlie structural and functional differences in excitatory spine synapses between forebrain, and cerebellum.

Animal cruelty has been a criminal offence in Hungary since 2004 and the legislator has tightened and differentiated the regulations in several waves since then. However, it is not an exaggeration to say that the public is often impatient and dissatisfied with the actions of the authorities in relation to animal cruelty. In our research, based on the data of the Criminal Investigation Department of the National Police Headquarters, we examined the opinions of 99 out of a total of 155 police stations in Hungary whose staff currently working there had experience in dealing with animal cruelty. The investigators gave their opinion on a total of 1169 cases in which some kind of police action was taken, either following a report to the police or as a result of their own investigative actions. In another survey, we questioned those members of society who are most committed to animal protection using a self-completion questionnaire. The questionnaire sent to the 116 Hungarian animal welfare non-governmental organisations (NGOs) on the publicly available lists was also posted for a short period on the social networking site of NGO activists. Among those who responded, a total of 150 identified as active participants in the animal protection work of these NGOs. The picture of the police treatment of animal cruelty, as perceived by NGOs working in the field of animal protection, is significantly less favourable than suggested by the police data. According to the official data, 77.7% of reports initiated an investigation, while the vast majority of animal welfare activists (81.3%) suspects that only 25% of the reports result in action by the prosecuting authority.

Background. Diabetes mellitus is closely related to both the severity of carotid disease and its outcome after revascularization. Carotid artery stenting (CAS) has emerged as a viable alternative to surgical endarterectomy but little is known about the impact of diabetes after CAS. Methods. A consecutive cohort of 1940 patients undergoing CAS in two institutions was divided into two groups, diabetics and nondiabetics, and major cerebrovascular events (MACCEs) were analyzed at 30 days post-CAS and at 1 year follow-up. Results. There were 730 patients with diabetes, with significantly higher BMI, hypertension, chronic dialysis, and dyslipidemia frequency (p

IntroductionFemoro-popliteal bypass with autologous vascular graft is a key revascularization method in chronic limb-threatening ischemia (CLTI). However, the lack of suitable autologous conduit may occur in 15-45% of the patients, necessitating the implantation of prosthetic or allogen grafts. Only little data is available on the outcome of allograft use in CLTI.AimsOur objective were to evaluate the long term results of infrainguinal allograft bypass surgery in patients with chronic limb-threatening ischemia (CLTI) and compare the results of arterial and venous allografts.MethodsSingle center, retrospective study analysing the outcomes of infrainguinal allograft bypass surgery in patients with CLTI between January 2007 and December 2017.ResultsDuring a 11-year period, 134 infrainguinal allograft bypasses were performed for CLTI [91 males (67.9%)]. Great saphenous vein (GSV) was implanted in 100 cases, superficial femoral artery (SFA) was implanted in 34 cases. Early postoperative complications appeared in 16.4% of cases and perioperative mortality (ConclusionAllograft implantation is a suitable method for limb salvage in CLTI. The patency of arterial allograft is better than venous allograft patency, especially in below-knee position during infrainguinal allograft bypass surgery.

Summary: Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan-extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that dietary spermidine passes the blood-brain barrier in mice and increases hippocampal eIF5A hypusination and mitochondrial function. Spermidine feeding in aged mice affects behavior in homecage environment tasks, improves spatial learning, and increases hippocampal respiratory competence. In a Drosophila aging model, spermidine boosts mitochondrial respiratory capacity, an effect that requires the autophagy regulator Atg7 and the mitophagy mediators Parkin and Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement of olfactory associative learning. This suggests that the maintenance of mitochondrial and autophagic function is essential for enhanced cognition by spermidine feeding. Finally, we show large-scale prospective data linking higher dietary spermidine intake with a reduced risk for cognitive impairment in humans.

IntroductionManagement of vascular infections represents a major challenge in vascular surgery. The use of cryopreserved vascular allografts could be a feasible therapeutic option, but the optimal conditions for their production and use are not precisely defined.AimsTo evaluate the effects of cryopreservation and the duration of storage on the thrombogenicity of femoral artery allografts.MethodsIn our prospective study, eleven multi-organ-donation-harvested human femoral arteries were examined at five time points during storage at -80°C: before cryopreservation as a fresh native sample and immediately, one, twelve and twenty-four weeks after the cryopreservation. Cross-sections of allografts were perfused with heparin-anticoagulated blood at shear-rates relevant to medium-sized arteries. The deposited platelets and fibrin were immunostained. The thrombogenicity of the intima, media and adventitia layers of the artery grafts was assessed quantitatively from the relative area covered by fibrin- and platelet-related fluorescent signal in the confocal micrographs.ResultsRegression analysis of the fibrin and platelet coverage in the course of the 24-week storage excluded the possibility for increase in the graft thrombogenicity in the course of time and supported the hypothesis for a descending trend in fibrin generation and platelet deposition on the arterial wall. The fibrin deposition in the cryopreserved samples did not exceed the level detected in any of the three layers of the native graft. However, an early (up to week 12) shift above the native sample level was observed in the platelet adhesion to the media.ConclusionsThe hemostatic potential of cryopreserved arterial allografts was retained, whereas their thrombogenic potential declined during the 6-month storage. The only transient prothrombotic change was observed in the media layer, where the platelet deposition exceeded that of the fresh native grafts in the initial twelve weeks after cryopreservation, suggesting a potential clinical benefit from antiplatelet therapy in this time-window.

Purpose: In previous clinical studies Digital Variance Angiography (DVA) provided higher signal-to-noise ratio (SNR) and better image quality than Digital Subtraction Angiography (DSA). Our aim was to investigate whether this quality reserve of DVA provides an opportunity for the reduction of iodinated contrast media (ICM) in carotid X-ray angiography (CXA). Method: Our prospective study enrolled 26 patients (67.0 ± 8.1 years) undergoing carotid percutaneous transluminal angioplasty. The SNR of DSA and DVA image pairs obtained by a standard (100 %, 6 mL ICM) or a low-dose (50 %, 3 mL ICM) protocol were compared. Visual evaluation of all images was performed by five specialists using a 5-grade rating scale. The quality of DSA100 and DVA50 videos was also compared. Results: DVA provided more than two-fold SNR, the median SNRDVA/SNRDSA ratio was 2.06 (100 %) and 2.25 (50 %). In the visual evaluation, the DVA100 score (3.73 ± 0.06) was significantly higher than the DSA100 score (3.52 ± 0.07, Wilcoxon p

Background: The image reconstruction of stenotic carotid bifurcation can be managed by medical practitioners and non-medical investigators with semi-automatic or manual segmentation. The outcome of blood flow simulations may vary because of a single mean voxel difference along the examined section, possibly more in the stenotic lesions, which can lead to conflicting results regarding other research findings. The aim of our project is computational geometry reconstruction for blood flow simulations to make it suitable for comparison with plaque image analysis performed by commercially available software. In this paper, a comparison is made between the manual and semi-automatic segmentations performed by non-medical and medical investigators, respectively. Methods: 30 patients were classified into three homogeneous groups. Our group classification was based on the following parameters: plaque calcification score, thickness, extent, remodeling and plaque localization. The images in the first group were segmented individually by medical practitioners and experienced non-medical investigators, the second group was segmented collectively, and the last group was segmented individually again. Cross-sections along the centerline were extracted, then geometrical and statistical analyses were performed. Exploratory flow simulations were carried out on two patients to showcase the effect of geometrical differences on the hemodynamic flow field. Results: The largest centerline-averaged voxel difference between the medical and non-medical investigators occurred in the first group with a positive difference of 1.16 voxels. In the second and third groups, the average voxel difference decreased to 0.65 and 0.75, respectively. The example case from the first group showed that the difference in maximum wall shear stress in the middle of the stenosis is 30% with an average voxel difference of 1.73. Meanwhile, it can decrease to 4% when the average voxel difference is 0.64 for the example case from the third group. Conclusions: A collective review of the medical images should preceded the manual segmentations before applying them in computational simulations in order to ensure a proper comparison with plaque image analysis. Especially complex pathology such as calcifications should be segmented under medical supervision or after specific training. Non-significant differences in the segmentation can lead to significant differences in the computed flow field.

By conveying signals from the small GTPase family of proteins to the Arp2/3 complex, proteins of the WAVE family facilitate actin remodeling. The WAVE-1 isoform is expressed at high levels in brain, where it plays a role in normal synaptic processing, and is implicated in hippocampus-dependent memory retention. We used electron microscopy to determine whether synaptic structure is modified in the hippocampus of WAVE-1 knockout mice, focusing on the neuropil of CA1 stratum radiatum. Mice lacking WAVE-1 exhibited alterations in the morphology of both axon terminals and dendritic spines; the relationship between the synaptic partners was also modified. The abnormal synaptic morphology we observed suggests that signaling through WAVE-1 plays a critical role in establishing normal synaptic architecture in the rodent hippocampus.

Assessment of variations in the use of lower extremity open vascular surgical procedures (LEOPEN) and lower extremity endovascular procedures (LEENDO) across small geographic areas in Hungary from 2013 to 2017. Introduction of a new metric giving a rough estimate of unwarranted clinical variation in revascularisation practice. Spatial variation (at local administrative unit level) of referral for LEOPEN and LEENDO was evaluated through a retrospective analysis using healthcare administrative data of all beneficiaries in Hungary. The same assessment was performed for percutaneous coronary intervention in acute myocardial infarction (PCIAMI). The latter was considered a reasonable comparator (similar at risk population, well organised, guideline driven patient pathways, small room for referral discretion). Consequently, the ratio of spatial variations of LEOPEN and LEENDO to PCIAMI (as a reference) are thought to reflect unwarranted clinical variation. A total of 109 882 procedures were identified in the database (LEOPEN, LEENDO, PCIAMI) affecting 85 083 patients. While estimates of spatial variations for LEOPEN and LEENDO turned out to be high (systematic component of variation [SCV] 0.09 and 0.21, respectively), PCIAMI showed a low SCV value of 0.02. Consequently, the ratios of SCVs were SCV/SCV ref = 4.67 (LEOPEN) and SCV/SCV ref = 10.3 (LEENDO), indicating high levels of unwarranted clinical variation. The analysis showed that patients living in different locations of Hungary face very different odds of having lower extremity revascularisation procedures (open or endovascular). This spatial variation is thought to be related mainly to the failure in vascular service organisation. The newly introduced numerical estimate of unwarranted clinical variation may support within, and also between, system comparisons. [ABSTRACT FROM AUTHOR]