Congenital growth hormone deficiency associated with hip dysplasia and Legg-Calve-Perthes disease

Objective: Growth hormone deficiency (GHD) is usually treated with recombinant human GH (rhGH), and this has been rarely associated with hip disorders. We analysed the clinical data of patients with congenital GHD receiving rhGH who had associated hip dysplasia or Legg‐Calve‐Perthes disease (LCPD), with a view to determining whether the hip dysplasia was associated with the underlying disease or with rhGH treatment. / Design: We performed a retrospective analysis of paediatric and adolescent patients seen between 1992–2018 with congenital GHD and hip disorders. Data were collected through a review of the patients’ medical records and included demographics, clinical and imaging data, and the time frame between the onset of the symptoms related to the hip disorders and the onset of GH treatment. / Results: Of the 13 patients with hip disorders, hip dysplasia was present in ten patients and LCPD in three. Hip dysplasia was diagnosed before rhGH was initiated in 50% of cases. These patients had bilateral hip dysplasia and isolated GHD. LCPD was diagnosed in one patient before rhGH was commenced and did not progress. In two patients, LCPD was diagnosed after rhGH was started and did temporarily progress in one of them, but rhGH was not discontinued because LCPD did not seem to be related to rhGH treatment. / Conclusions: This study suggests that hip dysplasia could be a manifestation of an underlying GHD. Additionally, rhGH treatment may not necessarily be causative of LCPD

Crosstalks of GSK3 signaling with the mTOR network and effects on targeted therapy of cancer

Abstract The introduction of therapeutics targeting specific tumor-promoting oncogenic or non-oncogenic signaling pathways has revolutionized cancer treatment. Mechanistic (previously mammalian) target of rapamycin (mTOR), a highly conserved Ser/Thr kinase, is a central hub of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR network, one of the most frequently deregulated signaling pathways in cancer, that makes it an attractive target for therapy. Numerous mTOR inhibitors have progressed to clinical trials and two of them have been officially approved as anticancer therapeutics. However, mTOR-targeting drugs have met with a very limited success in cancer patients. Frequently, the primary impediment to a successful targeted therapy in cancer is drug-resistance, either from the very beginning of the therapy (innate resistance) or after an initial response and upon repeated drug treatment (evasive or acquired resistance). Drug-resistance leads to treatment failure and relapse/progression of the disease. Resistance to mTOR inhibitors depends, among other reasons, on activation/deactivation of several signaling pathways, included those regulated by glycogen synthase kinase-3 (GSK3), a protein that targets a vast number of substrates in its repertoire, thereby orchestrating many processes that include cell proliferation and survival, metabolism, differentiation, and stemness. A detailed knowledge of the rewiring of signaling pathways triggered by exposure to mTOR inhibitors is critical to our understanding of the consequences such perturbations cause in tumors, including the emergence of drug-resistant cells. Here, we provide the reader with an updated overview of intricate circuitries that connect mTOR and GSK3 and we relate them to the efficacy (or lack of efficacy) of mTOR inhibitors in cancer cells

Survey and modelling for the bim of Basilica of San Marco in Venice

The Basilica of San Marco is a singular case in the field of Cultural heritage, as it constitutes a construction site always active for the maintenance and preservation of the basilica itself. The continuous intervention of conservation, due to the particular environmental conditions of Venice and the opening to the public, together with the complexity of the building itself, imposes the need to identify an optimized management system. For this reason, in 2013 the Procurator of St. Marco Basilica commissioned the construction of a 3D model of the Basilica to be used for the creation of a BIM. The model must meet the required precision of the scale of 1: 50, and should also include, in addition to the geometric description, a description of the mosaic and marble surfaces of the basilica through high resolution orthophoto which are essential for the restoration of the mosaics. The complexity of the church and the large and continuous flow of public led to work in non-optimal conditions especially for the acquisition stage. The basilica has certain peculiarities that led to some important choices, for example the use of photogrammetry instead of laser scanning technique. The same technique was preferred also by the need to realize, in addition to the geometric model, high-resolution orthophotos of marbles and mosaic surfaces. The modelling of the basilica has highlighted a number of problems related to the building features. The basilica, indeed, is the result of the juxtaposition of elements (capitals, columns) with different origin, which therefore cannot be standardized in special libraries. Moreover, especially in the extensive mosaic areas, there are not edges that characterize the architecture, but only beveled surfaces. This has resulted in a change also in the modeling paradigm with the need to identify alternative systems even for the construction of simple elements. Therefore, we decided to model using NURBS since it is the method that allows greater adherence to reality and, at the same time, a model with acceptable dimensions in terms of navigation and usability. Only the most sculptural pieces such as capitals and statues have been replaced by mesh models. As we were interested in different elaborations, the results of this work are a geometric NURBS model for the subsequent insertion into BIM environment, with the possibility of extracting two-dimensional drawings such as plans and sections, a mesh model with low resolution textures for online navigation and high resolution orthophotos. The survey work and modeling has been almost completed for the interior of the basilica whereas only the external remains to be acquired and modeled. For the management of the entire work it was decided to use the data organization system already used by the Politecnico di Milano for the Duomo di Milano. The BIM3DSURVEY system will be essential not only to manage the finished model, but it has been very useful also during the construction phase because it allows us to divide the entire work into more work units. However, this system required some changes to meet the peculiarity of this BIM, in particular the need to append and link the orthophotos to real surfaces, in order to use the model also as a spatial index for the images

Lymphectomy in the treatment of thyroid cancer in adults and children.

Thyroid carcinoma is thè most frequent endocrine malignancy in Italy and differs in naturai history according to histological type and age of patients. Lymph node metastases are more frequently seen in young patients with papillary carcinoma. However, many clinical series suggested that although thè incidence of lymph node invasion in high-risk patients (over-50s) is slightiy lower than in low-risk patients, thè locai recurrence rate is higher than in thè former. From thè results of our experience, confirmed by other authors, we retain total thyroidectomy with lymphectomy of thè centrai compartment as thè procedure of choice in thè treatment of well-differentiated thyroid carcinoma in thè under-50s. In thè over-50s, functional bilateral lymphectomy improves survival and should be considered mandatory, just as for medullary carcinoma. On thè contrary, thè prognosis of anaplastic carcinoma is not improved by lymphectomy

The 4 K outer cryostat for the CUORE experiment: construction and quality control

The external shell of the CUORE cryostat is a large cryogen-free system designed to host the dilution refrigerator and the bolometers of the CUORE experiment in a low radioactivity environment. The three vessels that form the outer shell were produced and delivered to the Gran Sasso underground Laboratories in July 2012. In this paper, we describe the production techniques and the validation tests done at the production site in 2012.Comment: 11 pages, 13 figures; to appear in NIM

Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL)

: The Hedgehog (HH) signaling network is one of the main regulators of invertebrate and vertebrate embryonic development. Along with other networks, such as NOTCH and WNT, HH signaling specifies both the early patterning and the polarity events as well as the subsequent organ formation via the temporal and spatial regulation of cell proliferation and differentiation. However, aberrant activation of HH signaling has been identified in a broad range of malignant disorders, where it positively influences proliferation, survival, and therapeutic resistance of neoplastic cells. Inhibitors targeting the HH pathway have been tested in preclinical cancer models. The HH pathway is also overactive in other blood malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). This review is intended to summarize our knowledge of the biological roles and pathophysiology of the HH pathway during normal T-cell lymphopoiesis and in T-ALL. In addition, we will discuss potential therapeutic strategies that might expand the clinical usefulness of drugs targeting the HH pathway in T-ALL

Breast meat traits of Muscovy ducks fed on a microalga (Crypthecodinium cohnii) meal supplemented diet

A trial was conducted in order to increase the docosahexaenoic acid ( DHA) content in the meat of Muscovy ducks ( Cairina moschata domestica L.) fed on a diet supplemented with the microalga Crypthecodinium cohnii. 2. Two diets were provided to 48 male and 48 female ducks, belonging to an Italian rural strain during the last 3 weeks of life: a maize - soybean based diet as the control diet and the same diet supplemented with 5 g/ kg microalga meal. 3. Dietary treatment did not induce differences in growth performances and slaughter traits. Similarly, chemical composition, colour, pH, oxidative stability and sensory characteristics of breast muscle were not influenced by the diet. 4. A significant increase of DHA content in breast meat of ducks fed on the Crypthecodinium cohnii enriched diet was observed

SINONASAL TUMOURS WITH ORBITAL INVOLVEMENT: THE COMBINED APPROACH

Advanced sinonasal tumours often present with orbital involvement. Surgical treatment and radical excision are also possible, preserving the eye. Oncological safety and functional outcome of the preserved eye are the counterpart in orbital preservation surgery. Irrespective of the orbital invasion, tumour histology influences the prognosis. Surgical approaches to the orbit in sinonasal tumour are divided in anterior and posterolateral procedures. The combined transfacial and trancranial surgical approaches have been well described in the literature for craniofacial resection, when the anterior or medium skull base are involved. Multidisciplinary collaboration with microscopic and/or endoscopic control have improved surgical technique to extirpate tumours extended to dura, spehenopalatine area and pterygomaxilmary fissure, infratemporal fossa, roof of nasopharynx and apex of orbit. We describe the multiphase combined surgical approach with maxillofacial, otolaryngology and neurosurgical collaboration in sinonasal tumour treatment

Analysis of the muscarinic receptor subtype mediating inhibition of the neurogenic contractions in rabbit isolated vas deferens by a series of polymethylene tetra-amines

1. The pharmacological characteristics of the presynaptic muscarinic receptor subtype, which mediates inhibition of the neurogenic contractions in the prostatic portion of rabbit vas deferens, have been investigated by using a series of polymethylene tetra-amines, which were selected for their ability to differentiate among muscarinic receptor subtypes. 2. It was found that all tetra-amines antagonized McN-A-343-induced inhibition in electrically stimulated rabbit vas deferens in a competitive manner and with affinity values (pA2) ranging between 6.27 ± 0.09 (spirotramine) and 8.51 ± 0.02 (AM170). 3. Competition radioligand binding studies, using native muscarinic receptors from rat tissues (M1, cortex; M2, heart; M3, submaxillary gland) or from NG 108-15 cells (M4) and human cloned muscarinic M1-M4 receptors expressed in CHO-K1 cells, were undertaken with the same tetraamines employed in functional assays. All antagonists indicated a one-site fit. 4. The affinity estimates (pKi) of tetra-amines calculated in binding assays using native receptors were similar to those obtained using cloned receptors. Among these compounds some displayed selectivity between muscarinic receptor subtypes, indicating that they may be valuable tools in receptor characterization. Spirotramine was selective for M1 receptors versus all other subtypes (pKi native: M1, 7.32 ± 0.10; M2, 6.50 ± 0.11; M3, 6.02 ± 0.13; M4, 6.28 ± 0.16; pKi cloned: M1, 7.69 ± 0.08; M2, 6.22 ± 0.14; M3, 6.11 ± 0.16; 6.35 ± 0.11) whereas CC8 is highly selective for M2 receptors versus the other subtypes (pKi native: M1 7.50 ± 0.04; M2, 9.01 ± 0.12; M3, 6.70 ± 0.08; M4, 7.56 ± 0.04; pKi cloned: M1, 7.90 ± 0.20; M2, 9.04 ± 0.08; M3, 6.40 ± 0.07; M4, 7.40 ± 0.04). Furthermore, particularly relevant for this investigation were tetra-amines dipitramine and AM172 for their ability to significantly differentiate M1 and M4 receptors. 5. The apparent affinity values (pA2) obtained for tetra-amines in functional studies using the prostatic portion of rabbit vas deferens correlated most closely with the values (pKi) obtained at either native or human recombinant muscarinic M4 receptors. This supports the view that the muscarinic receptor mediating inhibition of neurogenic contractions of rabbit vas deferens may not belong to the M1 type but rather appears to be of the M4 subtype