β-blockers : their new life from hypertension to cancer and migraine

The pharmacological class of \u3b2-blockers includes a plea of molecules with largely different pharmacokinetic and pharmacodynamic characteristics with a protective effect that may span far beyond the cardiovascular system. Although all these compounds share the pharmacological blockade of the adrenergic receptors, each of them is characterized by specific pharmacological properties, including selectivity of action depending on the adrenergic receptors subtypes, intrinsic sympathomimetic activity (ISA), lipid solubility, pharmacokinetic profile, and also other ancillary properties that impact their clinical effect. Their use in the treatment of hypertension has been extensively debated and at the moment a class indication is not present. However, in specific niche of patients, such as in those young individuals in which hypertension is mainly driven by a sympathetic hyperactivation, strong evidence pose \u3b2-Blockers as a highly reasonable \ufb01rst-line treatment. Lipophilic \u3b2-blockers, specifically propranolol and metoprolol, can cross the Blood Brain Barrier and have a Class A indication for the prophylactic treatment of migraine attacks. Moreover, since \u3b2-adrenergic receptors affect the proliferative process of both cancer and immune cells, their blockade has been associated with metastasis reduction in several epithelial and solid organ tumors posing \u3b2-Blockers as a new attractive, inexpensive and relatively safe therapeutic strategy in patients with several types of cancer. However, further dedicated prospective, randomized, placebo-controlled studies are needed to determine the real efficacy of these compounds

Stereotactic Irradiation of GH-Secreting Pituitary Adenomas

Radiotherapy (RT) is often employed in patients with acromegaly refractory to medical and/or surgical interventions in order to prevent tumour regrowth and normalize elevated GH and IGF-I levels. It achieves tumour control and hormone normalization up to 90% and 70% of patients at 10–15 years. Despite the excellent tumour control, conventional RT is associated with a potential risk of developing late toxicity, especially hypopituitarism, and its role in the management of patients with GH-secreting pituitary adenomas remains a matter of debate. Stereotactic techniques have been developed with the aim to deliver more localized irradiation and minimize the long-term consequences of treatment, while improving its efficacy. Stereotactic irradiation can be given in a single dose as stereotactic radiosurgery (SRS) or in multiple doses as fractionated stereotactic radiotherapy (FSRT). We have reviewed the recent published literature on stereotactic techniques for GH-secreting pituitary tumors with the aim to define the efficacy and potential adverse effects of each of these techniques

GSK-3 inhibition reverts mesenchymal transition in primary human corneal endothelial cells

Human corneal endothelial cells are organized in a tight mosaic of hexagonal cells and serve a critical function in maintaining corneal hydration and clear vision. Regeneration of the corneal endothelial tissue is hampered by its poor proliferative capacity, which is partially retrieved in vitro, albeit only for a limited number of passages before the cells undergo mesenchymal transition (EnMT). Although different culture conditions have been proposed in order to delay this process and prolong the number of cell passages, EnMT has still not been fully understood and successfully counteracted. In this perspective, we identified herein a single GSK-3 inhibitor, CHIR99021, able to revert and avoid EnMT in primary human corneal endothelial cells (HCEnCs) from old donors until late passages in vitro (P8), as shown from cell morphology analysis (circularity). In accordance, CHIR99021 reduced expression of α-SMA, an EnMT marker, while restored endothelial markers such as ZO-1, Na+/K+ ATPase and N-cadherin, without increasing cell proliferation. A further analysis on RNA expression confirmed that CHIR99021 induced downregulation of EnMT markers (α-SMA and CD44), upregulation of the proliferation repressor p21 and revealed novel insights into the β-catenin and TGFβ pathways intersections in HCEnCs. The use of CHIR99021 sheds light on the mechanisms involved in EnMT, providing a substantial advantage in maintaining primary HCEnCs in culture until late passages, while preserving the correct morphology and phenotype. Altogether, these results bring crucial advancements towards the improvement of the corneal endothelial cells based therapy

About the parabolic relation existing between the skewness and the kurtosis in time series of experimental data

In this work we investigate the origin of the parabolic relation between skewness and kurtosis often encountered in the analysis of experimental time-series. We argue that the numerical values of the coefficients of the curve may provide informations about the specific physics of the system studied, whereas the analytical curve per se is a fairly general consequence of a few constraints expected to hold for most systems.Comment: To appear in Physica Script

Comparing Radiotherapy Patient Flows in England and Italy

Research into radiotherapy patient flows in England and Italy investigated the degree of self-sufficiency in related service areas across each country. The respective results showed very different patterns, with there apparently being greater patient flow and less self-sufficiency for services in Italy, compared to England. However, close inspection suggested the results were not strictly comparable, despite the data, methodology and analyses being similar and entirely fitting in both cases. The respective studies were consequently compared for a range of criteria: how radiotherapy services are commissioned and provided; cultural expectations; base area definitions; data used; analyses undertaken; and research results. It was found that direct comparisons could not necessarily be drawn because cultural, conceptual, organisational and systemic factors in the delivery of services within each country influenced the results. Therefore, such factors should be taken into account when comparing health services in different countries, particularly in respect of patient flows and service self-sufficiency

Total phallic reconstruction after penile amputation for donkey bite: Case report and review of the literature

There are very few reported cases of traumatic amputation of the male genitalia due to animal bite. The management involves thorough washout of the wounds, debridement, antibiotic prophylaxis, tetanus and rabies immunization followed by immediate reconstruction or primary wound closure with delayed reconstruction, when immediate reconstruction is not feasible. When immediate reconstruction is not feasible, long-term good functional and cosmetic results are still possible in the majority of cases by performing total phallic reconstruction. In particular, it is now possible to fashion a cosmetically acceptable sensate phallus with incorporated neourethra, to allow the patient to void while standing and to ejaculate, and with enough bulk to allow the insertion of a penile prosthesis to guarantee the rigidity necessary to engage in penetrative sexual intercourse

Long-term results of laryngotracheal resection for benign stenosis from a series of 109 consecutive patients

OBJECTIVES: Long-term results of patients undergoing laryngotracheal resection for benign stenosis are reported. This is the largest series ever published. METHODS: Between 1991 and March 2015, 109 consecutive patients (64 males, 45 females; mean age 39 ± 10.9 years) underwent laryngotracheal resection for subglottic postintubation (93) or idiopathic (16) stenosis. Preoperative procedures included tracheostomy in 35 patients, laser in 17 and laser plus stenting in 18. The upper limit of the stenosis ranged between actual involvement of the vocal cords and 1.5 cm from the glottis. Airway resection length ranged between 1.5 and 6 cm (mean 3.4 ± 0.8 cm) and it was over 4.5 cm in 14 patients. Laryngotracheal release was performed in 9 patients (suprahyoid in 7, pericardial in 1 and suprahyoid + pericardial in 1). RESULTS: There was no perioperative mortality. Ninety-nine patients (90.8%) had excellent or good early results. Ten patients (9.2%) experienced complications including restenosis in 8, dehiscence in 1 and glottic oedema requiring tracheostomy in 1. Restenosis was treated in all 8 patients with endoscopic procedures (5 laser, 2 laser + stent, 1 mechanical dilatation). The patient with anastomotic dehiscence required temporary tracheostomy closed after 1 year with no sequelae. One patient presenting postoperative glottic oedema underwent permanent tracheostomy. Minor complications occurred in 4 patients (3 wound infections, 1 atrial fibrillation). Definitive excellent or good results were achieved in 94.5% of patients. Twenty-eight post-coma patients with neuropsychiatric disorders showed no increased complication and failure rate. CONCLUSIONS: Laryngotracheal resection is the definitive curative treatment for subglottic stenosis allowing very high success rate at long term. Early complications can be managed by endoscopic procedures achieving excellent and stable results over time

Nanoneedles Induce Targeted siRNA Silencing of p16 in the Human Corneal Endothelium

Nanoneedles can target nucleic acid transfection to primary cells at tissue interfaces with high efficiency and minimal perturbation. The corneal endothelium is an ideal target for nanoneedle-mediated RNA interference therapy aimed at enhancing its proliferative capacity, necessary for tissue regeneration. This work develops a strategy for siRNA nanoninjection to the human corneal endothelium. Nanoneedles can deliver p16-targeting siRNA to primary human corneal endothelial cells in vitro without toxicity. The nanoinjection of siRNA induces p16 silencing and increases cell proliferation, as monitored by ki67 expression. Furthermore, siRNA nanoinjection targeting the human corneal endothelium is nontoxic ex vivo, and silences p16 in transfected cells. These data indicate that nanoinjection can support targeted RNA interference therapy for the treatment of endothelial corneal dysfunction