An Almost Subharmonic Instability in the Flow Past Rectangular Cylinders

The three-dimensional instability of the flow past a 5 :1 rectangular cylinder is investigated via Floquet analysis and direct numerical simulations. A quasi-subharmonic (QS) unstable mode is detected, marking an important difference with the flow past bodies with lower aspect ratio and/or with smooth leading edge. The QS mode becomes unstable at Reynolds number (based on the cylinder thickness and free-stream velocity) Re approximate to 480; its spanwise wavelength is approximately three times the cylinder thickness. The structural sensitivity locates the wavemaker region over the longitudinal sides of the cylinder, indicating that the instability is triggered by the mutual inviscid interaction of vortices generated by the leading edge shear layer

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

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

Bilateral reconstruction of the mandibular body with symphyseal preservation using a single fibula free flap: operative technique

Background: Mandibular osteonecrosis may occur in 5% of the patients who undergo radiotherapy for the treatment of head and neck malignancies. Resection and microvascular reconstruction is the treatment of choice in complicated osteoradionecrosis, however multifocal presentation may complicate the management of the disease given the poor quality and limited availability of adequate recipient vessels. Operative technique: A 74-year-old man affected by multifocal severe osteoradionecrosis of the mandible underwent bilateral resection of the mandibular bodies while preserving the symphysis. The defects were reconstructed with a single fibula flap composed by two bony segments connected by a central segment, corresponding to the symphyseal region, in which the bone was dissected and removed. The anastomosis was performed on a single side of the neck. Healing was uneventful and the adopted technique allowed for a quick functional and esthetic recovery. Conclusion: The presented technique provided a safe and efficacious, although technically challenging, solution in a case presenting multifocal osteonecrosis of the jaw. The morbidity of the procedure was limited because the tissue resection and reconstruction processes were minimized. Graphical Abstract: [Figure not available: see fulltext.

Cellular senescence in vascular wall mesenchymal stromal cells, a possible contribution to the development of aortic aneurysm

Cellular senescence is a hallmark of ageing and it plays a key role in the development of age-related diseases. Abdominal aortic aneurysm (AAA) is an age related degenerative vascular disorder, characterized by a progressive dilatation of the vascular wall and high risk of rupture over time. Nowadays, no pharmacological therapies are available and the understanding of the molecular mechanisms that lead to AAA onset and development are poorly defined. In this study we investigated the cellular features of senescence in vascular mesenchymal stromal cells, isolated from pathological (AAA – MSCs) and healthy (h – MSCs) segments of human abdominal aorta and their implication in impairing the vascular repair ability of MSCs. Cell proliferation, ROS production, cell surface area, the expression of cyclin dependent kinase inhibitors p21CIP1 and p16INK4a, the activation of the DNA damage response and a dysregulated autophagy showed a senescent state in AAA - MSCs compared to h-MSCs. Moreover, a reduced ability to differentiate toward endothelial cells was observed in AAA – MSCs. All these data suggest that the accumulation of senescent vascular MSCs over time impairs their remodeling ability during ageing. This condition could support the onset and development of AAA