Relative echogenicity of tendons and ligaments of the palmar metacarpal region in foals from birth to 4 months of age: A longitudinal study

The objective of this study was to evaluate relative echogenicity of superficial and deep digital flexor tendons, the accessory ligament of the deep digital flexor tendon and interosseous muscle of the metacarpal region in foals ages 1 week to 4 months; and assess the association between echogenicity and sex or side/laterality. Seven Standardbred trotter foals were examined. Right and left metacarpal regions (palmar surface) were ultrasonographically investigated, and four regions of interest were assessed. A significant increase in echogenicity was seen in superficial and deep digital flexor tendons, accessory ligament of deep digital flexor tendon, and interosseous muscle during growth from 1 week to 4 months of age. Echogenicity of examined tendons and ligaments was not influenced by gender nor laterality. Reference values for tendon and ligament echogenicity could function as a tool to discriminate between physiological and abnormal conditions such as congenital contractural conditions

Patient-specific computational fluid dynamics of femoro-popliteal stent-graft thrombosis

Intra-stent thrombosis is one of the major failure modes of popliteal aneurysm endovascular repair, especially when the diseased arterial segment is long and requires overlapping stent-grafts having different nominal diameters in order to accommodate the native arterial tapering. However, the interplay between stent sizing, post-operative arterial tortuosity, luminal diameter, local hemodynamics, and thrombosis onset is not elucidated, yet. In the present study, a popliteal aneurysm was treated with endovascular deployment of two overlapped stent-grafts, showing intra-stent thrombosis at one-year follow-up examination. Patient-specific computational fluid-dynamics analyses including straight- and bent-leg position were performed. The computational fluid-dynamics analysis showed that the overlapping of the stent-grafts induces a severe discontinuity of lumen, dividing the stented artery in two regions: the proximal part, affected by thrombosis, is characterized by larger diameter, low tortuosity, low flow velocity, low helicity, and low wall shear stress; the distal part presents higher tortuosity and smaller lumen diameter promoting higher flow velocity, higher helicity, and higher wall shear stress. Moreover, leg bending induces an overall increase of arterial tortuosity and reduces flow velocity promoting furtherly the luminal area exposed to low wall shear stress

Impact of leg bending in the patient-specific computational fluid dynamics of popliteal stenting

Abstract Endovascular treatment of the femoro-popliteal artery has recently become a valuable therapeutic option for popliteal arterial aneurysms. However, its efficacy remains controversial due to the relatively high rate of complications, such as stent occlusion as result of intra-stent thrombosis. The elucidation of the interplay among vessel geometrical features, local hemodynamics, and leg bending seems crucial to understand onset and progression of popliteal intra-stent thrombosis. To this aim, patient-specific computational fluid dynamic simulations were performed in order to assess the intra-stent hemodynamics of two patients endovascularly treated for popliteal arterial aneurysm by stent-grafts and experiencing intra-stent thrombosis. Both Newtonian and non-Newtonian blood rheological models were considered. Results were presented in terms of tortuosity, luminal area exposed to low ( 1.5 Pa) time-averaged wall shear stress (TAWSS), area exposed to high (> 0.3) oscillatory shear index (OSI), and flow helicity. Study outcomes demonstrated that leg bending induced significant hemodynamic differences (> 50% increase) in both patients for all the considered variables, except for OSI in one of the two considered patients. In both leg configurations, stent-graft overlapping induced a severe discontinuity of the lumen diameter where the proximal stented zone is characterized by low tortuosity, low velocity, low helicity, low TAWSS, and high OSI; while the distal part has higher tortuosity, velocity, helicity, TAWSS, and lower OSI. Sensitivity study on applied boundary conditions showed that the different inlet velocity profiles for a given inlet waveform affect slightly the numerical solution; conversely, the shape and magnitude of the prescribed inlet waveform is determinant. Focusing on the comparison between the Newtonian and non-Newtonian blood models, the area with low TAWSS is greater in the Newtonian model for both patients, while no significant difference occurs between the surfaces with high TAWSS. GraphicAbstract Patient-specific computational fluid dynamic simulations were performed in order to assess the intra-stent hemodynamics of two patients endovascularly treated for popliteal arterial aneurysm and experiencing intra-stent thrombosis. Both Newtonian and non-Newtonian blood rheological models were considered. In both straight and bent leg configurations, stent-graft overlapping induced a severe discontinuity of the lumen diameter where the proximal stented zone is characterized by low tortuosity, low velocity, low helicity, low time-averaged wall shear stress (TAWSS), and high oscillatory index (OSI); while the distal part has higher tortuosity, velocity, helicity, TAWSS, and lower OSI

The human corneal epithelium after alcohol delamination: a structural and ultrastructural study

Dilute alcohol is one of the most popular methods for corneal epithelial removal during photorefractive keratectomy (PRK) and laser subepithelial keratomilieusis (LASEK). Even if the technique is used by nearly fifteen years, no concordant data are available on the effects of the exposition to dilute alcohol on the corneal epithelium. As in LASEK the epithelial flap obtained by the previous delamination is repositioned to improve corneal recovery, aim of the present work was to investigate the structure and the ultrastructure of the corneal epithelium after alcohol delamination. Ten patients undergoing PRK for myopic correction were consecutively included in the study. A 9-mm diameter cone was placed on the anaesthetized cornea and it was filled with 25% ethanol in BSS for 25 seconds. The cone was emptied and the corneal surface was washed off with BSS. The epithelial layer was lifted with beaver blade, peeled off with forceps, and processed for light (LM) and transmission electron microscopy (TEM). With LM, whilst superficial and wing cells showed a normal appearance, basal cells had significantly different staining patterns. In fact, in the same microscopic field they showed either normal morphology or paler nuclei and cytoplasm. When the specimens were observed with the TEM, all epithelial cells showed well-preserved intercellular spaces and junctional complexes. In the superficial cells perinuclear vacuolizations were present, whilst wing cells demonstrated no evident morphological changes. Clear basal cells had roundish nuclei with pale chromatin and clear cytoplasm with perinuclear endoplasmic reticulum and mitochondria and a large number of tonofilaments. Their basal membrane was generally intact, with many hemidesmosomes adhering to the basement membrane, which was formed only by the laminae lucida and densa. Dark basal cells showed irregular nuclei with condensed chromatin, vacuolated cytoplasm and few basal hemidesmosomes. Alcohol debridement can be considered as a valuable technique for removing corneal epithelium before PRK or for preparing an epithelial flap before LASEK: in fact it affects the binding of hemidesmosomes to the underlying basement membrane so that the lamina densa is separated from the lamina fibroreticularis. However, the observation of structural and ultrastructural changes of the basal cells, similar to those demonstrated in epithelial flaps obtained with the epikeratome, indicates the need for further studies to evaluate the corneal toxicity of the ethanol

Anti-Apolipoprotein A-1 auto-antibodies are active mediators of atherosclerotic plaque vulnerability

Aims Anti-Apolipoprotein A-1 auto-antibodies (anti-ApoA-1 IgG) represent an emerging prognostic cardiovascular marker in patients with myocardial infarction or autoimmune diseases associated with high cardiovascular risk. The potential relationship between anti-ApoA-1 IgG and plaque vulnerability remains elusive. Thus, we aimed to investigate the role of anti-ApoA-1 IgG in plaque vulnerability. Methods and results Potential relationship between anti-ApoA-1 IgG and features of cardiovascular vulnerability was explored both in vivo and in vitro. In vivo, we investigated anti-ApoA-1 IgG in patients with severe carotid stenosis (n = 102) and in ApoE−/− mice infused with polyclonal anti-ApoA-1 IgG. In vitro, anti-ApoA-1 IgG effects were assessed on human primary macrophages, monocytes, and neutrophils. Intraplaque collagen was decreased, while neutrophil and matrix metalloprotease (MMP)-9 content were increased in anti-ApoA-1 IgG-positive patients and anti-ApoA-1 IgG-treated mice when compared with corresponding controls. In mouse aortic roots (but not in abdominal aortas), treatment with anti-ApoA-1 IgG was associated with increased lesion size when compared with controls. In humans, serum anti-ApoA-1 IgG levels positively correlated with intraplaque macrophage, neutrophil, and MMP-9 content, and inversely with collagen. In vitro, anti-ApoA-1 IgG increased macrophage release of CCL2, CXCL8, and MMP-9, as well as neutrophil migration towards TNF-α or CXCL8. Conclusion These results suggest that anti-ApoA-1 IgG might be associated with increased atherosclerotic plaque vulnerability in humans and mic

The cornea in mucopolysaccharidosis IH-S: structural and ultrastructural study

Type I mucopolysaccharidoses (MPS I) include three autosomal recessive disorders (Hurler, MPS IH; Scheie, MPS IS; and Hurler-Scheie, MPS IH-S) caused by the deficient activity of the lysosomal hydrolase α-L-iduronidase with the consequent accumulation of dermatan and heparan sulfate in the lysosomes of several cell types [1]. MPS IH-S is an attenuated disease and the patients show minor facial and skeletal dysmorphism, regular intelligence, mild cardiac and respiratory disease, hepatosplenomegaly, and a normal lifespan. The most common feature is corneal opacification [2], whose morphological basis was not studied in detail. In this work we performed a structural and ultrastructural analysis of the cornea in a patient with MPS IH-S. The patient underwent penetrating keratoplasty and the corneal button was immediately processed for light and electron microscopy. From the micrographs a morphometric analysis was also performed. The corneal epithelium showed superficial cells with few microfolds and evident intercellular spaces. The wing cell layer was formed either by cells with well-evident tonofilaments and small peripheral clear vesicles, or with bilobed nucleus and large paranuclear vesicles filled with granular material. The basal cells showed polygonal shape, with many small vesicles, placed generally in the supranuclear cytoplasm: the intercellular space was enlarged by granular material. The Bowman’s layer was either normal in thickness and structure, or thinner and formed by granular material of variable electron density. The stroma was formed by irregular lamellae of differently oriented collagen, by a large number of keratocytes filled with vesicles, and by intercellular granular material. The corneal endothelium showed degenerative changes. The morphometric analysis of the collagen fibrils diameter provided a mean diameter of 21.71±2.09 nm. Hemidesmosomes were less numerous in the basal cells when compared to the normal cornea. Stromal keratocytes were reduced in their number, particularly in the anterior stroma. Our data showed in MPS IH-S patient pronounced changes of the epithelium, of the Bowman’s layer and of the stroma, consistent with the corneal opacity. As the etiology of the disease is a deficiency of α-L-iduronidase and the consequent accumulation of glycosaminoglycans, we are of the opinion that the stromal keratocytes are the first cells to be involved in the pathogenesis of the corneal disease. The accumulation of the aberrant products seems able to induce morphological changes of both the Bowman’s layer and the corneal epithelium

The activation of the cannabinoid receptor type 2 reduces neutrophilic protease-mediated vulnerability in atherosclerotic plaques

Aims The activation of cannabinoid receptor type 2 (CB2)-mediated pathways might represent a promising anti-atherosclerotic treatment. Here, we investigated the expression of the endocannabinoid system in human carotid plaques and the impact of CB2 pharmacological activation on markers of plaque vulnerability in vivo and in vitro. Methods and results The study was conducted using all available residual human carotid tissues (upstream and downstream the blood flow) from our cohort of patients symptomatic (n = 13) or asymptomatic (n = 27) for ischaemic stroke. Intraplaque levels of 2-arachidonoylglycerol, anandamide N-arachidonoylethanolamine, N-palmitoylethanolamine, N-oleoylethanolamine, and their degrading enzymes (fatty acid amide hydrolase and monoacylglycerol lipase) were not different in human plaque portions. In the majority of human samples, CB1 (both mRNA and protein levels) was undetectable. In downstream symptomatic plaques, CB2 protein expression was reduced when compared with asymptomatic patients. In these portions, CB2 levels were inversely correlated (r = −0.4008, P = 0.0170) with matrix metalloprotease (MMP)-9 content and positively (r = 0.3997, P = 0.0174) with collagen. In mouse plaques, CB2 co-localized with neutrophils and MMP-9. Treatment with the selective CB2 agonist JWH-133 was associated with the reduction in MMP-9 content in aortic root and carotid plaques. In vitro, pre-incubation with JWH-133 reduced tumour necrosis factor (TNF)-α-mediated release of MMP-9. This effect was associated with the reduction in TNF-α-induced ERK1/2 phosphorylation in human neutrophils. Conclusion Cannabinoid receptor type 2 receptor is down-regulated in unstable human carotid plaques. Since CB2 activation prevents neutrophil release of MMP-9 in vivo and in vitro, this treatment strategy might selectively reduce carotid vulnerability in human

Search for heavy neutral lepton production in K+ decays

A search for heavy neutral lepton production in K + decays using a data sample collected with a minimum bias trigger by the NA62 experiment at CERN in 2015 is reported. Upper limits at the 10−7 to 10−6 level are established on the elements of the extended neutrino mixing matrix |Ue4| 2 and |Uμ4| 2 for heavy neutral lepton mass in the ranges 170–448 MeV/c2 and 250–373 MeV/c2, respectively. This improves on the previous limits from HNL production searches over the whole mass range considered for |Ue4|2 and above 300 MeV/c2 for |Uμ4|2

Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments

The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations