BMP-induced non-canonical signaling is upregulated during autophagy-mediated regeneration in inflamed mesothelial cells.

Previously, we showed that after Freund's adjuvant-induced peritonitis, rat mesothelial cells regain their epithelial phenotype through mesenchymal-epithelial transition (MET) accompanied by autophagy. Since bone morphogenetic proteins (BMPs) are well-known MET-inducers, we were interested in the potential expression of BMPs and BMP-induced pathways. Although mesothelial cells expressed lower amounts of BMP7, its level in the peritoneal cavity and mesothelial synthesis of BMP4 were significantly increased during inflammation. BMPR1A and BMPR2 were also significantly expressed. Expression of transforming growth factor beta-activated kinase (TAK1) and c-Jun NH2-terminal kinases (JNK1-JNK2) were more intense than that of phosphorylated Mothers Against Decapentaplegic homolog 1/5 (p-SMAD1/5), confirming that the non-canonical pathway of BMPs prevailed in our model. JNK signaling through B-cell lymphoma-2 (Bcl-2) can contribute to Beclin-1 activation. We demonstrated that TAK1-JNK-Bcl-2 signaling was upregulated simultaneously with the autophagy-mediated regeneration. A further goal of our study was to prove the regenerative role of autophagy after inflammation. We used a specific inhibitor, bafilomycin A1 (BafA1), and found that BafA1 treatment decreased the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3B) and resulted in morphological signs of cell death in inflamed mesothelial cells indicating that if autophagy is arrested, regeneration turns into cell death and consequently, mesothelial cells die.

Diagnosis of Left-Sided Mechanical Prosthetic Valve Thrombosis: A Pictorial Review.

Although transcatheter valve therapy is rapidly evolving, surgical valve replacement is still required in many patients with severe left-side valve stenosis or regurgitation, the mechanical bi-leaflet heart valve being the standard prosthesis type in younger patients. Moreover, the prevalence of valvular heart disease is steadily increasing, especially in industrialized countries, and the problem of lifelong efficient anticoagulation of these patients remains fundamental, especially in the context where vitamin K antagonists continue to be the current standard of anticoagulation despite a level of oscillating anticoagulation. In this setting, avoiding prosthetic valve thrombosis after surgery is the number one objective for both the patient and the responsible physicians. Although rare, this complication is life threatening, with the sudden onset of acute cardiac failure such as acute pulmonary edema, cardiogenic shock, or sudden cardiac death and inadequate anticoagulation remaining the leading cause of prosthesis thrombosis, along with other risk factors. The availability of multimodal imaging techniques enables and encompasses to a full extent the diagnosis of mechanical valve thrombosis. The gold-standard diagnostic methods are transthoracic and transesophageal echocardiography. Moreover, 3D ultrasound has undoubted value in giving a more accurate description of the thrombus's extension. When transthoracic and transesophageal echocardiography are uncertain, the multidetector computer tomography examination is an important complementary imaging method. Fluoroscopy is also an excellent tool for evaluating the mobility of prosthetic discs. Each method complements the other to differentiate an acute mechanical valve thrombosis from other prosthetic valve pathologies such as pannus formation or infective endocarditis and aids the physician in accurately establishing the treatment method (surgical or pharmaceutical) and its optimal timing. The aim of this pictorial review was to discuss from an imagistic perspective the mechanical prosthetic aortic and mitral valve thrombosis and to provide an overview of the essential role of non-invasive exploration in the treatment of this severe complication.

The Role of Multimodality Imaging in the Diagnosis and Follow-Up of Malignant Primary Cardiac Tumors: Myxofibrosarcoma-A Case Report and Literature Review.

Cardiac tumors are a very rare but heterogenous group of diseases that may reveal themselves through a variety of nonspecific cardiac symptoms that may pose a challenge to the diagnostic process. Myxofibrosarcoma is a particularly rare type of cardiac tumor that carries a poor prognosis, thus making accurate and timely diagnosis essential. A 61-year-old woman presented with fatigue and shortness of breath during mild exercise, symptoms that have progressively worsened during the previous year. Multimodality imaging consisting of transthoracic and transesophageal echocardiography (TTE and TEE), cardiac magnetic resonance (CMR), cardiac computer tomography (CCT), and fluorodeoxyglucose positron emission computer tomography (18F-FDG PET-CT) was used for the diagnosis and postoperative follow-up of a myxofibrosarcoma.

The Role of Echocardiography in the Diagnosis of Cardiac Involvement in a Rare Systemic Condition: The Carcinoid Heart Disease: A Case Report and Review of Literature.

Carcinoid heart disease is a rare presentation of the carcinoid syndrome, which is caused by excessive tumoral hormone production and the abundant release of vasoactive substances with systemic expressions. A 62-year-old woman presented with flushing, diarrhea, weight loss, and right-sided heart failure symptoms. Specific carcinoid heart disease features were identified using transthoracic and transesophageal echocardiography at the tricuspid and pulmonic valves. Biomarkers, 99mTc-Tektrotyd scintigraphy, SPECT-CT, and a biopsy later confirmed the diagnosis, and the patient began treatment for the underlying condition.

Diagnostic Challenges in Rare Causes of Arrhythmogenic Cardiomyopathy-The Role of Cardiac MRI.

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare genetic condition of the myocardium, with a significantly high risk of sudden death. Recent genetic research and improved understanding of the pathophysiology tend to change the ARVD definition towards a larger spectrum of myocardial involvement, which includes, in various proportions, both the right (RV) and left ventricle (LV), currently referred to as ACM (arrhythmogenic cardiomyopathy). Its pathological substrate is defined by the replacement of the ventricular myocardium with fibrous adipose tissue that further leads to inadequate electrical impulses and translates into varies degrees of malignant ventricular arrythmias and dyskinetic myocardium movements. Particularly, the cardio-cutaneous syndromes of Carvajal/Naxos represent rare causes of ACM that might be suspected from early childhood. The diagnostic is sometimes challenging, even with well-established rTFC or Padua criteria, especially for pediatric patients or ACM with LV involvement. Cardiac MRI gain more and more importance in ACM diagnostic especially in non-classical forms. Furthermore, MRI is useful in highlighting myocardial fibrosis, fatty replacement or wall movement with high accuracy, thus guiding not only the depiction, but also the patient's stratification and management.

Primary Pericardial Synovial Sarcoma: A Case Report and Literature Review.

We report a case of a 52-year-old woman who was referred to our institution with a superior vena cava syndrome and was investigated through echocardiography, CT and MRI revealing a well-defined, encapsulated pericardial mass. The pathology, correlated with the immunohistochemical analysis, concluded it was an extremely rare primary pericardial synovial sarcoma. The patient underwent surgery and chemotherapy with a 16-month disease-free survival and passed away after a contralateral aggressive relapse. Moreover, we discuss the role of each imaging modality together with their pericardial synovial sarcoma reported features.

Transthyretin cardiac amyloidosis.

Transthyretin amyloid cardiomyopathy (ATTR-CM) may be an under recognized cause of heart failure (HF). TTR amyloidosis can be inherited, caused by variants in the TTR gene (ATTRv) or by deposition of wild-type TTR protein (ATTRwt), leading to high mortality if untreated. We report the case of a patient with hereditary TTR amyloidosis and mixed phenotype (both cardiac and neurological involvement). We highlight the importance of multimodal imaging in the evaluation of these patients, as early diagnosis and treatment might lead to better outcome.

Major Left Bundle Branch Block and Coronary Heart Disease-Are There Any Differences between the Sexes?

Left bundle branch block is not a benign pathology, and its presence requires the identification of a pathological substrate, such as ischemic heart disease. Left bundle branch block appears to be more commonly associated with normal coronary arteries, especially in women. The objectives of our study were to describe the particularities of left bundle branch block in women compared to men with ischemic heart disease. Result: We included seventy patients with left bundle branch block and ischemic heart disease, with a mean age of 67.01 ± 8.89 years. There were no differences in the profile of risk factors, except for smoking and uric acid. The ventricular depolarization (QRS) duration was longer in men than women (136.86 ± 8.32 vs. 132.57 ± 9.19 msec; p = 0.018) and also men were observed to have larger left ventricular diameters. Left bundle branch block duration was directly associated with ventricular diameters and indirectly associated with left ventricular ejection fraction value, especially in women (R = -0.52, p = 0.0012 vs. R = -0.50, p = 0.002). In angiography, 80% of women had normal epicardial arteries compared with 65.7% of men; all these patients presented with microvascular dysfunction. Conclusion: The differences between the sexes were not so obvious in terms of the presence of risk factors; instead, there were differences in electrocardiographic, echocardiographic, and angiographic aspects. Left bundle branch block appears to be a marker of microvascular angina and systolic dysfunction, especially in women.

Pd-Oxazolone complexes conjugated to an engineered enzyme: improving fluorescence and catalytic properties.

Different Pd-complexes containing orthometallated push-pull oxazolones were inserted by supramolecular Pd-amino acid coordination on two genetically engineered modified variants of the thermoalkalophilic Geobacillus thermocatenolatus lipase (GTL). Pd-lipase conjugation was performed on the solid phase in the previously immobilized form of GTL under mild conditions, and soluble conjugated Pd-GTL complexes were obtained by simply desorbing by washing with an acetonitrile aqueous solution. Three different Pd complexes were incorporated into two different genetically modified enzyme variants, one containing all the natural cysteine residues changed to serine residues, and another variant including an additional Cys mutation directly in the catalytic serine (Ser114Cys). The new Pd-enzyme conjugates were fluorescent even at ppm concentrations, while under the same conditions free Pd complexes did not show fluorescence at all. The Pd conjugation with the enzyme extremely increases the catalytic profile of the corresponding Pd complex from 200 to almost 1000-fold in the hydrogenation of arenes in aqueous media, achieving in the case of GTL conjugated with orthopalladated 4a an outstanding TOF value of 27 428 min-1. Also the applicability of GTL-C114 conjugated with orthopalladated 4b in a site-selective C-H activation reaction under mild conditions has been demonstrated. Therefore, the Pd incorporation into the enzyme produces a highly stable conjugate, and improves remarkably the catalytic activity and selectivity, as well as the fluorescence intensity, of the Pd complexes.

The role of multimodal imaging in the diagnosis of an asymptomatic patient with congenital anomaly.

Anomalous left coronary artery from the pulmonary artery (ALCAPA) syndrome is a rare congenital coronary anomaly, which can cause potentially fatal complications, such as heart failure, myocardial infarction and sudden cardiac death. Only a few patients left untreated survive to adulthood. We highlight the importance of multimodal imaging in the diagnosis of ALCAPA syndrome in a young asymptomatic female patient with inducible ischemia on exercise. The patient was successfully treated with surgery.

Diagnostic Dilemma of Recurrent Pulmonary Embolism.

Popliteal venous aneurysms are rare vascular disorders associated with a high risk of pulmonary embolism. We present the case of a 56-year-old woman hospitalized for a third episode of unprovoked pulmonary embolism. Venous ultrasonography identified a popliteal aneurysm, repeatedly missed by two-point compression venous ultrasonography, which was eventually confirmed by a magnetic resonance examination. Because of its highly symptomatic nature despite optimal anticoagulant treatment, the decision was made to undergo surgery, consisting of aneurysmectomy followed by patch angioplasty. The goal of this paper is to report a rare case of popliteal venous aneurysm and its treatment strategies and postoperative evolution.

High-frequency ultrasonography of psoriatic skin: A non-invasive technique in the evaluation of the entire skin of patients with psoriasis: A pilot study.

Psoriasis is a chronic, systemic, inflammatory disorder which accelerates the life process of skin cells, based on a genetically induced deviant immune response. High-frequency ultrasonography (HF-USG) is a painless, non-invasive imaging technique that can be performed and repeated whenever the need arises. We evaluated lesional and non-lesional skin of psoriatic patients with the use of HF-USG, focusing on the immune-induced inflammation and skin thickness. Previous studies suggested that HF-USG, being a non-invasive technique, is useful as an aid to clinical evaluation of the severity of psoriatic plaques. Our goal was to determine whether the skin of psoriatic patients is influenced by the background or habits of the patients. The study included a total of 27 patients affected by psoriasis vulgaris. The thickness of the epidermis and dermis and the skin echogenicity were documented for the active plaques, as well as for the non-affected skin of all the patients included in the study, using a high-frequency ultrasonographic system. The patient's local background, sex, family history of psoriasis, smoking habits and sun exposure were analyzed. HF-USG of the psoriatic plaques exposes a three-band structure that is easily distinguished from the surrounding unaffected skin, due to a hypoechoic band in the upper dermis. Although not specific for psoriasis, it is a strong marker of inflammation. The obtained results confirm that, indeed, skin thickness is greater in lesional skin compared to non-lesional skin, by a mean of 1,180 µm (±340 µm). We consider that skin HF-USG should be used as a quantitative method in the clinical evaluation of the patients with psoriasis and may help as an objective means of assessing inflammation in lesional skin.

Immunohistochemical study of psoriatic plaques and perilesional skin in psoriasis vulgaris patients: A pilot study.

Psoriasis vulgaris, a chronic inflammatory skin disorder, is the result of immune mediated processes, genetic background and environmental factors. Prolactin and the vascular endothelial growth factor seem to play a key role in psoriasis pathogenesis regarding hyperproliferation of epidermal keratinocytes and dermal vascular ectasia. The aim of the study was to investigate the expression of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor receptor 2 (VEGFR2) and prolactin receptor (PRLR) in psoriatic skin by immunohistochemical analysis and to evaluate the correlation with disease severity. Two skin biopsies, psoriatic lesion and perilesional skin, obtained by punch biopsy from 19 nontreated psoriasis patients were examined in hematoxylin and eosin staining and immunohistochemistry (IHC) for TNF-α, VEGFR2 and PRLR. The indirect IHC reaction was carried out automatically and visualized by 3,3-diaminobenzidine (DAB) technique. The average number of DAB-positive cells and the intensity of cell staining were quantified on a predefined scale. The results show a significant difference in the quantity and distribution of TNF-α positive cells in the two sample groups. In psoriatic plaque skin, an increased expression of TNF-α was found in the perivascular dermis and epidermic keratinocytes. In perilesional skin the immunostaining was predominant in the basal layer keratinocytes, while in psoriatic plaque, all the layers were positively marked, with stronger expression at the base. A statistically significant difference was found between the intensity of the immunostaining in the two types of tissue. Positive cells for VEGFR2 and PRL were identified in the basal layer keratinocyte cells (VEGFR2), sweat glands and hair outer shaft sheath (PRLR), without significant differences between the two types of samples. Our findings confirm the importance of TNF-α in psoriasis pathogenesis and a positive correlation with lesions severity. No significant differences were found for VEGFR2 and PRLR, but additional studies are necessary to establish their role.

Cadmium complexes bearing Me2N

Heteroleptic zinc and cadmium complexes of the type [{Me2N^E^OR2}M-Nu]n (M = Zn, Cd; E = S, Se; R = CH3, CF3; Nu = N(SiMe3)2, I, Cl; n = 1-2) were prepared by reacting the alcohol proteo-ligands {Me2N^E^OR2}H with [M(N(SiMe3)2)2] (M = Zn, Cd) or [XMN(SiMe3)2] (M = Zn, X = Cl; M = Cd, X = I) in an equimolar ratio. These group 12 metal complexes were characterised in solution by multinuclear NMR spectroscopy and their solid-state structures were determined by X-ray diffractometry. The ligands {Me2N^E^O(CH3)2}- bearing CH3 groups in α position to the alkoxide behave as κ2-O,E-bidentate moieties (E = S, Se) and form centro-symmetric dinuclear O-bridged heteroleptic alkoxo-amido complexes both with zinc and cadmium, with four-coordinate metal centres resting in tetrahedral environments. By contrast, complexes supported by the CF3-substituted {Me2N^E^O(CF3)2}- crystallise as tetrahedral mononuclear species, with tridentate κ3-N,O,E-coordinated ligands. These structural differences resulting from changes in the ligand skeleton and in the electron-donating properties of the alkoxide were also observed in solution. Attempts to prepare congeneric heteroleptic mercury complexes from [Hg(N(SiMe3)2)2] unexpectedly only afforded homoleptic bis(alkoxide)s such as [{Me2N^S^O(CF3)2}2Hg]. Owing to the strong Hg-C bond, treatment of [PhHgN(SiMe3)2] with {Me2N^S^O(CF3)2}H afforded the heteroleptic, T-shaped [{Me2N^S^O(CF3)2}HgPh] mercuric alkoxide upon elimination of hexamethyldisilazane. [{Me2N^S^O(CF3)2}2Hg] and [{Me2N^S^O(CF3)2}HgPh] constitute very rare examples of structurally characterised mercuric alkoxides.