Toward a better understanding of tool wear effect through a comparison between experiments and SPH numerical modelling of machining hard materials

The aim of this study is to improve the general understanding of tungsten carbide (WC–Co) tool wear under dry machining of the hard-to-cut titanium alloy Ti6Al4V. The chosen approach includes experimental and numerical tests. The experimental part is designed to identify wear mechanisms using cutting force measurements, scanning electron microscope observations and optical profilometer analysis. Machining tests were conducted in the orthogonal cutting framework and showed a strong evolution of the cutting forces and the chip profiles with tool wear. Then, a numerical method has been used in order to model the machining process with both new and worn tools. The use of smoothed particle hydrodynamics model (SPH model) as a numerical tool for a better understanding of the chip formation with worn tools is a key aspect of this work. The redicted chip morphology and the cutting force evolution with respect to the tool wear are qualitatively compared with experimental trends. The chip formation mechanisms during dry cutting process are shown to be quite dependent from the worn tool geometry. These mechanisms explain the high variation of the experimental and numerical feed force between new and worn tools

Short-term cryoprotectant-free cryopreservation at −20°C does not affect the viability and regenerative capacity of nanofat

Nanofat is an autologous fat derivative with high regenerative activity, which is usually administered immediately after its generation by mechanical emulsification of adipose tissue. For its potential repeated use over longer time, we herein tested whether cryopreservation of nanofat is feasible. For this purpose, the inguinal fat pads of donor mice were processed to nanofat, which was i) frozen and stored in a freezer at −20°C, ii) shock frozen in liquid nitrogen with subsequent storage at −80°C or iii) gradually frozen and stored at −80°C. After 7 days, the cryopreserved nanofat samples were thawed and immunohistochemically compared with freshly generated nanofat (control). Nanofat frozen and stored at −20°C exhibited the lowest apoptotic rate and highest densities of blood and lymph vessels, which were comparable to those of control. Accordingly, nanofat cryopreserved at −20°C or control nanofat were subsequently fixed with platelet-rich plasma in full-thickness skin defects within dorsal skinfold chambers of recipient mice to assess vascularization, formation of granulation tissue and wound closure by means of stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over 14 days. These analyses revealed no marked differences between the healing capacity of wounds filled with cryopreserved or control nanofat. Therefore, it can be concluded that cryopreservation of nanofat is simply feasible without affecting its viability and regenerative potential. This may broaden the range of future nanofat applications, which would particularly benefit from repeated administration of this autologous biological product

The Efficacy of Tetracyclines in Peripheral and Intracerebral Prion Infection

We have previously shown that tetracyclines interact with and reverse the protease resistance of pathological prion protein extracted from scrapie-infected animals and patients with all forms of Creutzfeldt-Jakob disease, lowering the prion titre and prolonging survival of cerebrally infected animals. To investigate the effectiveness of these drugs as anti-prion agents Syrian hamsters were inoculated intramuscularly or subcutaneously with 263K scrapie strain at a 10−4 dilution. Tetracyclines were injected intramuscularly or intraperitoneally at the dose of 10 mg/kg. A single intramuscular dose of doxycycline one hour after infection in the same site of inoculation prolonged median survival by 64%. Intraperitoneal doses of tetracyclines every two days for 40 or 44 days increased survival time by 25% (doxycycline), 32% (tetracycline); and 81% (minocycline) after intramuscular infection, and 35% (doxycycline) after subcutaneous infection. To extend the therapeutic potential of tetracyclines, we investigated the efficacy of direct infusion of tetracyclines in advanced infection. Since intracerebroventricular infusion of tetracycline solutions can cause overt acute toxicity in animals, we entrapped the drugs in liposomes. Animals were inoculated intracerebrally with a 10−4 dilution of the 263K scrapie strain. A single intracerebroventricular infusion of 25 µg/ 20 µl of doxycycline or minocycline entrapped in liposomes was administered 60 days after inoculation, when 50% of animals showed initial symptoms of the disease. Median survival increased of 8.1% with doxycycline and 10% with minocycline. These data suggest that tetracyclines might have therapeutic potential for humans

Nanofat Accelerates and Improves the Vascularization, Lymphatic Drainage and Healing of Full-Thickness Murine Skin Wounds

The treatment of wounds using the body’s own resources is a promising approach to support the physiological regenerative process. To advance this concept, we evaluated the effect of nanofat (NF) on wound healing. For this purpose, full-thickness skin defects were created in dorsal skinfold chambers of wild-type mice. These defects were filled with NF generated from the inguinal subcutaneous adipose tissue of green fluorescent protein (GFP)+ donor mice, which was stabilized using platelet-rich plasma (PRP). Empty wounds and wounds solely filled with PRP served as controls. Wound closure, vascularization and formation of granulation tissue were repeatedly analyzed using stereomicroscopy, intravital fluorescence microscopy, histology and immunohistochemistry over an observation period of 14 days. PRP + NF-treated wounds exhibited accelerated vascularization and wound closure when compared to controls. This was primarily due to the fact that the grafted NF contained a substantial fraction of viable GFP+ vascular and lymph vessel fragments, which interconnected with the GFP− vessels of the host tissue. Moreover, the switch from inflammatory M1- to regenerative M2-polarized macrophages was promoted in PRP + NF-treated wounds. These findings indicate that NF markedly accelerates and improves the wound healing process and, thus, represents a promising autologous product for future wound management

Present and future of kidney replacement therapy in Italy: the perspective from Italian Dialysis and Transplantation Registry (IDTR)

Incidence of kidney replacement therapy (KRT) stabilizes or declines both in Europe and in the US; however, it is predictable that global prevalence of KRT will double by 2030. In this paper, we focus on the patterns of incidence, mortality, and prevalence of KRT in Italy, and we compare, when possible, the findings with other countries. The Italian Dialysis and Transplantation Registry (IDTR) currently collects aggregate data from regional registries. In Italy, KRT yearly incidence is around 160 patients per million population (pmp). This incidence showed an increasing trend up until 2011 with an average annual percentage change (AAPC) of 1.8%, after which it stabilized. Older age is an important determinant for KRT incidence, and it is strongly associated with the variability between Italian regions. Incidence is very stable within patients less than 50 years old; however, it greatly differs between regions for patients over 75 years old, ranging from 400 to 900 pmp. Moreover, the incidence for patients over 50 years old declined from 366 pmp in 2011 to 285 in 2017. An age-period-cohort (APC) model showed a very strong cohort effect, which shows the decline in incidence seems mainly due to the better health conditions of people born after 1940. Mortality rate in KRT patients was 109 per 1000 patient-year (py) between 2011 and 2017 with great differences among treatment modalities: 162 per 1000 py in haemodialysis, 117 per 1000 py in peritoneal dialysis, and 16 per 1000 py in kidney transplantation. Premature death is better detected by the standard expected years of life lost (YLL). The distribution of YLL rate per age shows a sharp increase between 40 and 70 years old both in haemodialysis and peritoneal dialysis patients with an AAPC of 5.2% and 4.1% respectively. Transplanted patients experience a very low YLL rate at any age. KRT prevalence was 1118 pmp in 2017 and it should be close to 1175 pmp by 2025 with a projected increase of transplanted patients\u2019 prevalence to 500 pmp, and a decrease of dialysis patients from 714 to 680 pmp. The proportion of patients treated with one of the three modalities strictly depends on age, with a sharp increase of haemodialysis after the age of 50. All data suggests the necessity to improve the care of middle and older age patients who experience the higher incidence of disease and mortality