Diabetic peripheral neuropathic pain is a stronger predictor of depression than other diabetic complications and comorbidities.

Aims: To investigate the independent effect on depression of painless diabetic polyneuropathy, painful diabetic polyneuropathy, and general and diabetes-related comorbidities. Methods: In 181 patients, the presence of painless diabetic polyneuropathy, painful diabetic polyneuropathy, comorbidities and depression was assessed using the Michigan Neuropathy Screening Instrument Questionnaire, the Michigan Diabetic Neuropathy Score, nerve conduction studies, the Douleur Neuropathique en 4 Questions, the Charlson Comorbidity Index and the Beck Depression Inventory-II. Results: In all, 46 patients met the criteria of confirmed painless diabetic polyneuropathy and 25 of painful diabetic polyneuropathy. Beck Depression Inventory-II scores indicative of mild-moderate-severe depression were reached in 36 patients (19.7%). In a multiple logistic regression analysis (including age, sex, body mass index, being unemployed, duration, haemoglobin A1c, insulin treatment, systolic blood pressure, nephropathy, retinopathy, Charlson Comorbidity Index and painful diabetic polyneuropathy), female sex (odds ratio: 5.9, p = 0.005) and painful diabetic polyneuropathy (odds ratio: 4.6, p = 0.038) were the only independent predictors of depression. Multiple regression analysis, including Douleur Neuropathique en 4 Questions and Michigan Diabetic Neuropathy Score instead of painful diabetic polyneuropathy, showed that Douleur Neuropathique en 4 Questions, in addition to female sex, was a significant predictor of depressive symptoms severity (p =0.005). Conclusion: Painful diabetic polyneuropathy is a greater determinant of depression than other diabetes-related complications and comorbidities. Painful symptoms enhance depression severity more than objective insensitivity

Surgical treatment of post-menopausal ovarian hyperandrogenism improves glucometabolic profile alongside clinical hirsutism

Hyperandrogenism during menopause is often underestimated by clinicians and attributed to the natural aging process. Hyperandrogenism can be associated with some metabolic abnormalities linked together in a vicious circle by insulin resistance. We present the case of an elderly woman affected with type 2 diabetes and obesity who reported the occurrence of clinical hirsutism after physiological menopause at the age of 47 years. At presentation, physical examination and Ferriman-Gallwey score revealed a condition of moderate hirsutism, with markedly increased levels of plasma testosterone and delta-4-androstenedione, obesity (body mass index 31.9), and inadequate glycemic control (glycated hemoglobin 65 mmol/mol). The patient underwent a thorough differential diagnosis by a multidisciplinary team approach, including the various causes of hyperandrogenism during menopause. After choosing surgical option as the appropriate treatment, clinical resolution of hirsutism was observed alongside patient satisfaction and marked improvement of the glucometabolic profile

Perifosine as a Potential Novel Anti-Cancer Agent Inhibits EGFR/MET-AKT Axis in Malignant Pleural Mesothelioma

PI3K/AKT signalling pathway is aberrantly active and plays a critical role for cell cycle progression of human malignant pleural mesothelioma (MMe) cells. AKT is one of the important cellular targets of perifosine, a novel bio-available alkylphospholipid that has displayed significant anti-proliferative activity in vitro and in vivo in several human tumour model systems and is currently being tested in clinical trials.We tested Perifosine activity on human mesothelial cells and different mesothelioma cell lines, in order to provide evidence of its efficacy as single agent and combined therapy.We demonstrate here that perifosine, currently being evaluated as an anti-cancer agent in phase 1 and 2 clinical trials, caused a dose-dependent reduction of AKT activation, at concentrations causing MMe cell growth arrest. In this study we firstly describe that MMe cells express aside from AKT1 also AKT3 and that either the myristoylated, constitutively active, forms of the two proteins, abrogated perifosine-mediated cell growth inhibition. Moreover, we describe here a novel mechanism of perifosine that interferes, upstream of AKT, affecting EGFR and MET phosphorylation. Finally, we demonstrate a significant increase in cell toxicity when MMe cells were treated with perifosine in combination with cisplatin.This study provides a novel mechanism of action of perifosine, directly inhibiting EGFR/MET-AKT1/3 axis, providing a rationale for a novel translational approach to the treatment of MMe

Mg-substituted hydroxyapatite nanopowders: Synthesis, thermal stability and sintering behaviour

This paper reports a systematic investigation on Mg-substituted hydroxyapatite (Ca10−xMgx(PO4)6(OH)2) nanopowders produced by precipitation of Ca(NO3)2·4H2O and Mg(NO3)2. The Mg content ranged between 0.6 and 2.4 wt%. Semicrystalline Mg-substituted hydroxyapatite powders made up of needle-like nanoparticles were obtained, the specific surface area ranged between 87 and 142m2/g. Pure hydroxyapatite nanopowder decomposed around 1000 ◦C. Mg-substituted hydroxyapatites were thermally stable up to 660 ◦C (x=1.0), 760 ◦C (x=0.5) and 840 ◦C (x=0.25) showing a distinct decreased thermal stability with respect to the pure sample. A relevant displacement of the sintering curve at lower temperature as a function of Mg content was observed, comparing to the behaviour of a pure HAp material, synthesized following the same procedure, and ascribed to the -TCP formatio

Si-substituted hydroxyapatite nanopowders: synthesis, thermal stability and sinterability

Synthetic hydroxyapatites incorporating small amounts of Si have shown improved biological performances in terms of enhanced bone apposition, bone in-growth and cell-mediated degradation. This paper reports a systematic investigation on Si-substituted hydroxyapatite (Si 1.40 wt%) nanopowders produced following two different conventional wet methodologies: (a) precipitation of Ca(NO3)2.4H2O and (b) titration of Ca(OH)2. The influence of the synthesis process on composition, thermal behaviour and sinterability of the resulting nanopowders is studied. Samples were characterised by electron microscopy, induced coupled plasma atomic emission spectroscopy, thermal analysis, infrared spectroscopy, N2 adsorption measurements, X-ray diffraction and dilatometry. Semicrystalline Si-substituted hydroxyapatite powders made up of needle-like nanoparticles were obtained, the specific surface area ranged between 84 and 110 m2/g. Pure and Sisubstituted hydroxyapatite nanopowders derived from Ca(NO3)2.4H2O decomposed around 1000 °C. Si-substituted hydroxyapatite nanopowders obtained from Ca(OH)2 were thermally stable up to 1200 °C and showed a distinct decreased thermal stability with respect to the homologous pure sample. Sisubstituted hydroxyapatites exhibited higher sintering temperature and increased total shrinkage with respect to pure powders. Nanostructured dense ceramics were obtained by sintering at 1100 °C Sisubstituted hydroxyapatites derived from Ca(OH)

Thermal Stability and sintering behaviour of hydroxyapatite nanopowders

Hydroxyapatite (HA) nanopowders were synthesised following two different precipitation routes: (a) from calcium nitrate and diammonium hydrogen phosphate solutions and (b) from calcium hydroxide suspension and phosphoric acid solution. The influence of precipitation process, concentration, and synthesis temperature on HA particle size and morphology, phase composition, thermal stability, and sintering behaviour was investigated by means of: thermogravimetry and differential thermal analysis (TG-DTA), induced coupled plasma-atomic emission spectroscopy (ICP-AES), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), electron microscopy (TEM, SEM) and dilatometry

Nanostructured F-substituted hydroxyapatite

Hydroxyapatite and F-halfsubstituted hydroxyapatite nanopowders were obtained by precipitation. Particle size and morphology were studied by TEM and specific surface area measured by N2 adsorption. Characteristic functional groups were evidenced by FT-IR, thermal behavior followed by DTA and thermal stability evaluated by XRD. Crystallinity degree, average crystallite size and cell parameters were calculated. Density and microstructure of sintered ceramics were also determined

Synthesis and characterization of Mg-substituted hydroxyapatite nanopowders

Hydroxyapatite and Mg-substituted hydroxyapatite nanopowders were obtained by precipitation. Composition was determined by ICP-AES and specific surface area measured by N2 adsorption. Characteristic functional groups were evidenced by FT-IR and thermal behaviour followed by DTA. Thermal stability evaluated by XRD and HT-XRD. Crystallinity degree, average crystallite size and cell parameters were calculated. Density and microstructure of sintered ceramics were also determined

Si-substituted hydroxyapatite nanopowders by precipitation: Synthesis, thermal stability, and sintering behaviour

Synthetic hydroxyapatites incorporating small amounts of Si show improved biological performances in terms of enhanced bone apposition, bone in-growth and cell-mediated degradation. Si-substituted hydroxyapatite (Si 1.40 % wt) nanopowders were synthesised by titration of Ca(OH)2. Samples were characterized by electron microscopy, induced coupled plasma-atomic emission spectroscopy, thermal analysis, infrared spectroscopy, N2 adsorption measurements, X-ray diffraction and dilatometry