Omnidirectional and broadband photon harvesting in self-organized Ge columnar nanovoids.

Highly porous Germanium surfaces with uniformly distributed columnar nanovoid structures are fabricated over a large area (wafer scale) by large fluence Sn+irradiation through a thin silicon nitride layer. The latter represents a one-step highly reproducible approach with no material loss to strongly increase photon harvesting into a semiconductor active layer by exploiting the moth-eye antireflection effect. The ion implantation through the nitride cap layer allows fabricating porous nanostructures with high aspect ratio, which can be tailored by varying ion fluence. By comparing the reflectivity of nanoporous Ge films with a flat reference we demonstrate a strong and omnidirectional reduction in the optical reflectivity by a factor of 96% in the selected spectral regions around 960 nm and by a factor of 67.1% averaged over the broad spectral range from 350 to 1800 nm. Such highly anti-reflective nanostructured Ge films prepared over large-areas with a self-organized maskless approach have the potential to impact real world applications aiming at energy harvesting.

Quantization of Acoustic Modes in Dumbbell Nanoparticles.

The vibrational eigenmodes of dumbbell-shaped polystyrene nanoparticles are recorded by Brillouin light spectroscopy (BLS), and the full experimental spectra are calculated theoretically. Different from spheres with a degeneracy of (2l+1), with l being the angular momentum quantum number, the eigenmodes of dumbbells are either singly or doubly degenerate owing to their axial symmetry. The BLS spectrum reveals a new, low-frequency peak, which is attributed to the out-of-phase vibration of the two lobes of the dumbbell. The quantization of acoustic modes in these molecule-shaped dumbbell particles evolves from the primary colloidal spheres as the separation between the two lobes increases.

Raman Open Database: first interconnected Raman-X-ray diffraction open-access resource for material identification.

Detailed crystallographic information provided by X-ray diffraction (XRD) is complementary to molecular information provided by Raman spectroscopy. Accordingly, the combined use of these techniques allows the identification of an unknown compound without ambiguity. However, a full combination of Raman and XRD results requires an appropriate and reliable reference database with complete information. This is already available for XRD. The main objective of this paper is to introduce and describe the recently developed Raman Open Database (ROD, http://solsa.crystallography.net/rod). It comprises a collection of high-quality uncorrected Raman spectra. The novelty of this database is its interconnectedness with other open databases like the Crystallography Open Database (http://www.crystallography.net/cod and Theoretical Crystallography Open Database (http://www.crystallography.net/tcod/). The syntax adopted to format entries in the ROD is based on the worldwide recognized and used CIF format, which offers a simple way for data exchange, writing and description. ROD also uses JCAMP-DX files as an alternative format for submitted spectra. JCAMP-DX files are compatible to varying degrees with most commercial Raman software and can be read and edited using standard text editors.

Extrahepatic autoimmunity in autoimmune liver disease.

The most important autoimmune liver disease include: autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. In general, about one in three patients with an autoimmune liver disease have a concomitant extrahepatic autoimmune disease, which may include rheumatological, endocrinological, gastrointestinal, pulmonary or dermatological conditions. The pathogenesis of these conditions includes the production of both innate and adaptive immune responses targeting cholangiocytes as well as different extrahepatic tissues. In this sense, extrahepatic autoimmunity represent a continuous spectrum of autoimmunity involving liver and extrahepatic tissues. This review aims to focus the clinical and pathophysiological aspects of extrahepatic autoimmunity associated to autoimmune liver diseases.

Etiopathogenesis of autoimmune hepatitis.

Autoimmune hepatitis is a chronic inflammatory liver disease characterized by hypergammaglobulinemia, the presence of autoantibodies, and inflammation within the liver, including lymphocytic infiltrates and interface hepatitis. Autoimmune hepatitis shows a female predominance and can present at any age and in any ethnicity. The disease is thought to be a consequence of a break of immune tolerance leading to an autoimmune process that induces liver injury. The self-attack is triggered by T-helper cell-mediated liver autoantigen recognition and B-cell production of autoantibodies, and is sustained by impaired regulatory T cells number and function. Superimposed on a genetic predisposition, infections and environmental factors have been studied as triggering factors for the disease. Allelic variants in the HLA locus have been associated with susceptibility; associations with single nucleotide polymorphisms within non-HLA genes have also been assessed. Several factors have been described as triggers of autoimmune responses in predisposed individuals, including infections, alcohol, vitamin D deficiency, and an altered composition of the intestinal microbiome. Importantly, drugs and herbal agents may trigger classical autoimmune hepatitis, or may induce a liver disease with autoimmune features. Interactions between female hormones and genetic factors have been hypothesized to play a role in autoimmunity, although the exact role for these factors has not been fully established. Herein we present a review of the etiology of autoimmune hepatitis including de novo autoimmune hepatitis post-liver transplantation as well as animal models for its study.

The Close Relationship between Large Bowel and Heart: When a Colonic Perforation Mimics an Acute Myocardial Infarction.

Colonoscopic perforation is a serious and potentially life-threatening complication of colonoscopy. Its incidence varies in frequency from 0.016% to 0.21% for diagnostic procedures, but may be seen in up to 5% of therapeutic colonoscopies. In case of extraperitoneal perforation, atypical signs and symptoms may develop. The aim of this report is to raise the awareness on the likelihood of rare clinical features of colonoscopic perforation. A 72-year-old male patient with a past medical history of myocardial infarction presented to the emergency department four hours after a screening colonoscopy with polypectomy, complaining of neck pain, retrosternal oppressive chest pain, dyspnea, and rhinolalia. Right chest wall and cervical subcutaneous emphysema, pneumomediastinum, pneumoretroperitoneum, and bilateral subdiaphragmatic free air were reported on the chest and abdominal X-rays. The patient was treated conservatively, with absolute bowel rest, total parental nutrition, and broad-spectrum intravenous antibiotics. Awareness of the potentially unusual clinical manifestations of retroperitoneal perforation following colonoscopy is crucial for the correct diagnosis and prompt management of colonoscopic perforation. Conservative treatment may be appropriate in patients with a properly prepared bowel, hemodynamic stability, and no evidence of peritonitis. Surgical treatment should be considered when abdominal or chest pain worsens, and when a systemic inflammatory response arises during the conservative treatment period.

Direct observation of polymer surface mobility via nanoparticle vibrations.

Measuring polymer surface dynamics remains a formidable challenge of critical importance to applications ranging from pressure-sensitive adhesives to nanopatterning, where interfacial mobility is key to performance. Here, we introduce a methodology of Brillouin light spectroscopy to reveal polymer surface mobility via nanoparticle vibrations. By measuring the temperature-dependent vibrational modes of polystyrene nanoparticles, we identify the glass-transition temperature and calculate the elastic modulus of individual nanoparticles as a function of particle size and chemistry. Evidence of surface mobility is inferred from the first observation of a softening temperature, where the temperature dependence of the fundamental vibrational frequency of the nanoparticles reverses slope below the glass-transition temperature. Beyond the fundamental vibrational modes given by the shape and elasticity of the nanoparticles, another mode, termed the interaction-induced mode, was found to be related to the active particle-particle adhesion and dependent on the thermal behavior of nanoparticles.

Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury.

Heparanase (HPSE) is part of the biologic network triggered by ischemia/reperfusion (I/R) injury, a complication of renal transplantation and acute kidney injury. During this period, the kidney or graft undergoes a process of macrophages recruitment and activation. HPSE may therefore control these biologic effects. We measured the ability of HPSE and its inhibitor, SST0001, to regulate macrophage polarization and the crosstalk between macrophages and HK-2 renal tubular cells during in vitro hypoxia/reoxygenation (H/R). Furthermore, we evaluated in vivo renal inflammation, macrophage polarization, and histologic changes in mice subjected to monolateral I/R and treated with SST0001 for 2 or 7 d. The in vitro experiments showed that HPSE sustained M1 macrophage polarization and modulated apoptosis, the release of damage associated molecular patterns in post-H/R tubular cells, the synthesis of proinflammatory cytokines, and the up-regulation of TLRs on both epithelial cells and macrophages. HPSE also regulated M1 polarization induced by H/R-injured tubular cells and the partial epithelial-mesenchymal transition of these epithelial cells by M1 macrophages. All these effects were prevented by inhibiting HPSE. Furthermore, the inhibition of HPSE in vivo reduced inflammation and M1 polarization in mice undergoing I/R injury, partially restored renal function and normal histology, and reduced apoptosis. These results show for the first time that HPSE regulates macrophage polarization as well as renal damage and repair after I/R. HPSE inhibitors could therefore provide a new pharmacologic approach to minimize acute kidney injury and to prevent the chronic profibrotic damages induced by I/R.-Masola, V., Zaza, G., Bellin, G., Dall'Olmo, L., Granata, S., Vischini, G., Secchi, M. F., Lupo, A., Gambaro, G., Onisto, M. Heparanase regulates the M1 polarization of renal macrophages and their crosstalk with renal epithelial tubular cells after ischemia/reperfusion injury.

Heparanase and macrophage interplay in the onset of liver fibrosis.

The heparan sulfate endoglycosidase heparanase (HPSE) is involved in tumor growth, chronic inflammation and fibrosis. Since a role for HPSE in chronic liver disease has not been demonstrated to date, the current study was aimed at investigating the involvement of HPSE in the pathogenesis of chronic liver injury. Herein, we revealed that HPSE expression increased in mouse livers after carbon tetrachloride (CCl4)-mediated chronic induction of fibrosis, but with a trend to decline during progression of the disease. In mouse fibrotic liver tissues HPSE immunostaining was restricted in necro-inflammatory areas, co-localizing with F4/80 macrophage marker and TNF-α. TNF-α treatment induced HPSE expression as well as HPSE secretion in U937 macrophages. Moreover, macrophage-secreted HPSE regulated the expression of α-SMA and fibronectin in hepatic stellate LX-2 cells. Finally, HPSE activity increased in the plasma of patients with liver fibrosis but it inversely correlated with liver stiffness. Our results suggest the involvement of HPSE in early phases of reaction to liver damage and inflammatory macrophages as an important source of HPSE. HPSE seems to play a key role in the macrophage-mediated activation of hepatic stellate cells (HSCs), thus suggesting that HPSE targeting could be a new therapeutic option in the treatment of liver fibrosis.

Recent data concerning heparanase: focus on fibrosis, inflammation and cancer.

Heparanase (HPSE) is a multitasking protein characterized by enzymatic and non-enzymatic activities. By means of its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thereby inducing the remodeling of the extracellular matrix and basement membranes. Thanks to the cleavage of HS, HPSE also promotes the release and diffusion of several HS-linked molecules such as growth factors, cytokines and enzymes. In addition to degrading HS chains, HPSE has non-enzymatic functions that trigger several signaling pathways. This signaling activity is achieved by interacting with transmembrane proteins, activating kinases such as Akt and Src, or modulating the activity of factors such as FGF-2 and TGF-ß. Several studies have recently highlighted a possible intracellular activity for HPSE, particularly at nuclear level. While HPSE activity is quite limited in physiological conditions, its demonstrated increasing involvement in various pathological conditions, such as in tumor progression and renal disease, have attracted the attention of a growing number of researchers. The fact that no other molecule is capable of performing the same function as HPSE makes this enzyme an attractive potential target of medical treatment. With this short conceptual overview, we aim to provide an update on current knowledge concerning the HPSE protein in the experimental and clinical settings, paying particular attention to its role in fibrosis, inflammation and cancer.

Heparanase is a key player in renal fibrosis by regulating TGF-ß expression and activity.

Epithelial-mesenchymal transition (EMT) of tubular cells is one of the mechanisms which contribute to renal fibrosis and transforming growth factor-ß (TGF-ß) is one of the main triggers. Heparanase (HPSE) is an endo-ß-D-glucuronidase that cleaves heparan-sulfate thus regulating the bioavailability of growth factors (FGF-2, TGF-ß). HPSE controls FGF-2-induced EMT in tubular cells and is necessary for the development of diabetic nephropathy in mice. The aim of this study was to investigate whether HPSE can modulate the expression and the effects of TGF-ß in tubular cells. First we proved that the lack of HPSE or its inhibition prevents the increased synthesis of TGF-ß by tubular cells in response to pro-fibrotic stimuli such as FGF-2, advanced glycosylation end products (AGE) and albumin overload. Second, since TGF-ß may derive from sources different from tubular cells, we investigated whether HPSE modulates tubular cell response to exogenous TGF-ß. HPSE does not prevent EMT induced by TGF-ß although it slows its onset; indeed in HPSE-silenced cells the acquisition of a mesenchymal phenotype does not develop as quickly as in wt cells. Additionally, TGF-ß induces an autocrine loop to sustain its signal, whereas the lack of HPSE partially interferes with this autocrine loop. Overall these data confirm that HPSE is a key player in renal fibrosis since it interacts with the regulation and the effects of TGF-ß. HPSE is needed for pathological TGF-ß overexpression in response to pro-fibrotic factors. Furthermore, HPSE modulates TGF-ß-induced EMT: the lack of HPSE delays tubular cell transdifferentiation, and impairs the TGF-ß autocrine loop.

Heparanase as a target in cancer therapy.

Heparanase is the unique and specific functional endoglycosidase capable of cleaving heparan sulfate (HS) chains. It exerts its enzymatic activity catalyzing the cleavage of the ß (1,4)-glycosidic bond between glucuronic acid and glucosamine residue. HS cleavage results in remodelling of the extracellular matrix as well as in regulating the release of many HS-linked molecules such as growth factors, cytokines and enzymes involved in inflammation, wound healing and tumour invasion. A pro-metastatic and pro-angiogenic role for this enzyme has been widely demonstrated in many primary human tumours since high levels of heparanase correlate with lymph node and distant metastasis, elevated micro vessel density and reduced survival of cancer patients. Recently, data have been reported that heparanase regulates heparan sulfate proteoglycan syndecan-1 and promotes its shedding from the cell surface. Shed syndecan-1 in turn controls tumour growth, metastasis and neo-angiogenesis mainly by promoting growth-factor signaling in the tumour milieu. Considering that, once inactivated, there are no other molecules capable of performing the same function, it is evident how this enzyme may be an effective and attractive drug target. Several heparanase inhibitors have been developed and some of them have undergone clinical trials showing efficacy against tumours. In this mini-review we will discuss current knowledge of heparanase involvement in cancer as well as its targeted inhibition as a promising therapeutic option in tumour treatment.

Long-term effects of intermittent Iloprost infusion on pulmonary arterial pressure in connective tissue disease.

BACKGROUND: Intravenous periodic Iloprost is proven effective in the treatment of Raynaud phenomenon (RP) related to connective tissue disorder (CTD). It's well known that synthetic prostaglandins are effective drugs for the treatment of pulmonary arterial hypertension (PAH), and that PAH is frequently associated with CTD. OBJECTIVE: The aim of the study is to evaluate in the chronic effect of cyclic intravenous Iloprost on pulmonary arterial pressure. METHODS: We studied 17 consecutive patients with CTD (14 systemic sclerosis, 3 mixed CTD) and RP, at the entry and after at least 6months of treatment of RP with cyclic Iloprost. On both occasions, in all patients we performed transthoracic Doppler echocardiography and we determined NT-proBNP plasma levels, NYHA functional class, 6 Minute-Walk Distance (6MWD). RESULTS: At follow-up (8.2±1.9months; range 6-12) mean values of pulmonary arterial systolic pressure (PASP) significantly decreased (from 32.2±9.2 to 29.2±7.6mmHg, p<0.04) and mean values of 6MWD significantly increased (from 407.5±101.5 to 448.3±89.9m, p<0.01). Moreover, we observed a significant direct correlation between PASP and NT-proBNP values and a significant inverse correlation both between NT-proBNP and 6MWD values and between PASP and 6MWD values. CONCLUSION: Our results suggest that cyclic intravenous Iloprost may protect against the development or worsening of PAH in patients with CTD and RP.

Sildenafil therapy for interferon-ß-1a-induced pulmonary arterial hypertension: a case report.

Interferon (IFN) therapy is nowadays widely used in clinical practice. In the literature, there are very few reports of the association between IFN therapy and pulmonary arterial hypertension (PAH), and current guidelines do not mention IFNs as a risk factor for PAH. We describe a patient with multiple sclerosis who developed severe PAH after treatment with IFN-ß-1a and the clinical response to sildenafil. Furthermore, we stress the need to further investigate the link between IFNs and PAH.

[Takayasu arteritis with aortic coarctation and multiple stenosis of aortic branches]. / Arterite di Takayasu tipo coartazione aortica con stenosi multidistrettuali di diramazioni aortiche principali.

The authors discuss the diagnostic and therapeutic implication regarding the clinical case of a young woman with hypertension due to atypical coarctation type Takayasu arteritis with impressive stenosis of renal arteries, of the proximal segment of celiac tripod and of superior mesenteric artery.

Pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease with significant disability and mortality, and it has much higher prevalence than previously thought. During the past 15 years, we have witnessed remarkable advances in our understanding of pathogenesis, in diagnostic process and in the development of disease-specific treatments for PAH. Nowadays, the diagnosis is more clearly defined, non-invasive markers of disease severity can be widely applied, and finally we can adopt evidence-based treatment. Newer drugs availability has resulted in radical change in the management of this disease. The article reviews established approaches to evaluation and treatment of this disorder.

Raynaud's phenomenon and plasma endothelin: correlations with capillaroscopic patterns in systemic sclerosis.

OBJECTIVE: We evaluated endothelin (ET)-1 plasma levels and some clinical measures in patients with primary Raynaud's phenomenon (PRP), and in patients with systemic sclerosis (SSc) and secondary RP (SRP), in the latter according to their different nailfold videocapillaroscopy (NVC) patterns of microangiopathy (early, active, and late). METHODS: Ninety-nine patients with SSc, 49 with PRP, and 45 control subjects were studied. NVC was performed in all patients to distinguish the pattern of microvascular damage, and the morphological alterations were scored by a semiquantitative rating scale. ET-1 plasma levels were evaluated in all individuals by ELISA. RESULTS: ET-1 plasma levels were significantly higher (p=0.001) in patients with both PRP and SRP, compared to controls. A significant positive correlation (p=0.03) was found between ET-1 plasma levels and SRP duration, but not between ET-1 plasma levels and PRP duration. Significant correlations were observed in patients with SSc between ET-1 plasma levels and clinical measures (e.g., digital ulcers), as well as the score value of single NVC measures, such as the number of capillaries, "ramified" capillaries, and enlarged capillaries (p<0.05). Finally, the highest ET-1 plasma levels were found in patients with SSc showing the late pattern of microangiopathy when compared to the early pattern (p=0.03) and to controls (p=0.003). CONCLUSION: Highest ET-1 plasma levels were detected in the more advanced stage of the SSc microangiopathy, namely the late NVC pattern, characterized by capillary loss and increased tissue fibrosis; this might support the involvement of ET-1 in the progression of the microvascular/fibrotic SSc damage.

Capillaroscopy.

Capillaroscopy is the most reliable way to distinguish between primary and secondary Raynaud's phenomenon (RP) through identification of an early pattern of systemic sclerosis (SSc). The presence of giant capillaries and microhaemorrhages on nailfold videocapillaroscopy (NVC) is sufficient to identify the scleroderma pattern (early), and an increase in these features and the addition of loss of capillaries (active pattern) is followed by neo-angiogenesis, fibrosis and 'desertification' (late pattern). The sensitivity of the American College of Rheumatology's classification criteria for SSc increases from 67% to 99% with the addition of these specific NVC abnormalities. Based on the appearance of the scleroderma pattern on NVC, almost 15% of patients shift from primary to secondary RP over a mean follow-up period of 29.4+/-10 months. Follow-up by NVC (every 6 months) is suggested for RP patients. A scoring system for NVC changes is available, and scores change significantly during follow-up of SSc patients. Several other NVC patterns have also been identified, such as in dermatomyosistis, systemic lupus eythaematosus, mixed connective tissue disease and antiphospholipid syndrome.

Use of glucocorticoids and risk of infections.

Glucocorticoids (GC) exert many complex quantitative and qualitative immunosuppressive effects that induce cellular immunodeficiency and consequently might increase host susceptibility to various viral, bacterial, fungal, and parasitic infections. In chronic immune/inflammatory conditions cortisol is secreted at inadequate levels and GC therapy today is devoted in substituting this hormone in adequate doses (low) to compensate just for this; therefore, the correct timing of GC administration, such as given during the turning-on phase of TNF secretion (night), can be of major importance. Consequently, the use of the lowest possible GC dose, at the night time and even for the shortest possible time, should decrease dramatically the risk of infections.