Electron beam melting of Ti-6Al-4V lattice structures: correlation between post heat treatment and mechanical properties

Additive manufacturing processes are considered advanced manufacturing methods. It would be possible to produce complex shape components from a computer-aided design model in a layer-by-layer manner. As one of the complex geometries, lattice structures could attract lots of attention for both medical and industrial applications. In these structures, besides cell size and cell type, the microstructure of lattice structures can play a key role in these structures’ mechanical performance. On the other hand, heat treatment has a significant influence on the mechanical properties of the material. Therefore, in this work, the effect of the heat treatments on the microstructure and mechanical behaviour of Ti-6Al-4V lattice structures manufactured by electron beam melting was analysed. The main mechanical properties were compared with the Ashby and Gibson model. It is very interesting to notice that a more homogeneous failure mode was found for the heat-treated samples. The structures’ relative density was the main factor influencing the mechanical performance of the heat-treated samples. It is also found that the heat treatments were able to preserve the stiffness and the compressive strength of the lattice structures. Besides, an increment of both the elongation at failure and the absorbed energy was obtained after the heat treatments. Microstructure analysis of the heat-treated samples confirms the increment of ductility of the heat-treated samples with respect to the as-built one

a cephalometric intercentre comparison of patients with unilateral cleft lip and palate at 5 and 10 years of age

SUMMARY The aim of this study was to evaluate any differences between the craniofacial growth of unilateral cleft lip and palate (UCLP) patients who underwent surgery in the Milan CLP centre with those from the Oslo CLP centre at 5 and 10 years of age. The Milan sample comprised 88 UCLP patients (60 males, 28 females) at 5 years of age and 26 patients (17 males, 9 females) at 10 years of age all operated on by the same surgeon. The Oslo sample consisted of 48 UCLP patients (26 males, 22 females) aged 5 years and 29 patients (20 males, 9 females) aged 10 years treated by four different surgeons. Lateral cephalometric radiographs obtained for both samples were analysed and angular measurements and ratios were calculated both for the hard and soft tissues. Statistical analysis was undertaken with an unpaired t -test. At 5 years of age, there were neither sagittal nor vertical hard tissue differences between the two groups. With regard to the soft tissues, only the naso-labial angle showed a statistically signifi cant difference (Milan greater than Oslo by 5 degrees, P 2.6 degrees, P 2.9 degrees, P < 0.001, respectively. At 5 years of age, the Milan UCLP sample had the same maxillary protrusion as the Oslo group, while at 10 years of age, the Milan sample were slightly less protruded than the Oslo group

Intraoperative cell salvage in ruptured abdominal aortic aneurysms

Aim. The aim of this study was to evaluate the impact of intraoperative cell salvage (ICS) on the early outcome after open repair (OR) of ruptured abdominal aortic aneurysm (rAAA). Methods. This is a retrospective review of 73 consecutive patients who underwent emergency OR of infrarenal rAAA with ICS between 2005 and 2008 (Group I), compared to 51 repairs from 2002-2004 with no ICS (Group II). In addition, a transfusion protocol of platelets and fresh frozen plasma (FFP) administration on admission and during surgery was adopted in patients in Group I to maintain coagulation competence. Results. ICS reduced bank blood demand by 63.6% (from 11 to 4 units, P<0.001) compared to controls, and had a strong impact on rates of postoperative complications (P=0.05), or death (43.8% vs. 52.9%, P<0.05) or in-hospital LOS (P<0.07) in these patients. Patients surviving in Group I had significantly higher postoperative haemoglobin level (11.5 vs. 9.6 g/dL, P<0.05) and platelet count (267 vs. 95 x 109 L, P<0.001 ), a shorter APTT (31 s vs. 47 s, P<0.05) and a lower INR (1.3 vs. 2.1, P<0.01) than patients who died postoperatively. ICS volume was significantly higher in patients with suprarenal aortic clamping and in those who had bifurcated grafting reconstruction (P<0.05), but amount of red blood cells (RBC) collected did not influence outcome. Conclusion. These results suggest that intraoperative cell salvage, minimizing perioperative homologous blood transfusion, is an important determinant of outcome after rAAA repair. Combined administration of balanced blood components may contribute to improve the survival of the patient

Cardiovascular comorbidities and pharmacological treatments of covid-19 patients not requiring hospitalization

Introduction: The Coronavirus disease 2019 (COVID-19) outbreak is a whole Earth health emergency related to a highly pathogenic human coronavirus responsible for severe acute respiratory syndrome (SARS-CoV-2). Despite the fact that the majority of infected patients were managed in outpatient settings, little is known about the clinical characteristics of COVID-19 patients not requiring hospitalization. The aim of our study was to describe the clinical comorbidity and the pharmacological therapies of COVID-19 patients managed in outpatient settings. Materials and Methods: We performed an observational, retrospective analysis of laboratory-confirmed COVID-19 patients managed in outpatient settings in Naples, Italy between March 9 and May 1, 2020. Data were sourced from the prospectively maintained Health Search (HS)/Thales database, shared by 128 primary care physicians (PCPs) in Naples, Italy. The clinical features and pharmacological therapies of COVID-19 patients not requiring hospitalization and managed in outpatient settings have been described. Results: A total of 351 laboratory-confirmed COVID-19 patients (mean age 54 ± 17 years; 193 males) with outpatient management were evaluated. Hypertension was the most prevalent comorbidity (35%). The distribution of cardiovascular comorbidities showed no gender-related differences. A total of 201 patients (57.3%) were treated with at least one experimental drug for COVID-19. Azithromycin, alone (42.78%) or in combination (27.44%), was the most widely used experimental anti-COVID drug in outpatient settings. Low Molecular Weight Heparin and Cortisone were prescribed in 24.87% and 19.4% of the study population, respectively. At multivariate regression model, diabetes (risk ratio (RR): 3.74; 95% CI 1.05 to 13.34; p = 0.04) and hypertension (RR: 1.69; 95% CI 1.05 to 2.7; p = 0.03) were significantly associated with the experimental anti-COVID drug administration. Moreover, only diabetes (RR: 2.43; 95% CI 1.01 to 5.8; p = 0.03) was significantly associated with heparin administration. Conclusions: Our data show a high prevalence of hypertension, more likely treated with renin– angiotensin–aldosterone system (RASS) inhibitors, among COVID-19 patients not requiring hospitalization. Experimental COVID-19 therapies have been prescribed to COVID-19 patients considered at risk for increased venous thromboembolism based on concomitant comorbidities, in particular diabetes and hypertension

Cracking behaviour of high-strength AA2024 aluminium alloy produced by Laser Powder Bed Fusion

Most wrought aluminium alloys of the 2000 series are difficult to manufacture by laser powder bed fusion (L-PBF) due to the formation of cracks during building. To date, the effects of processing regimes on crack formation are still not well understood. In this study we performed a detailed microstructural characterisation of crack development in the AlCuMg alloy AA2024 to quantify the extent of cracking and porosity arising from a range of different process parameters. Two samples, produced with different build parameters, were selected for in-depth study by scanning and transmission electron microscopy; these had similar low levels of porosity but high (H - 2.6 ± 0.4 mm/mm2) and low (L - 1.5 ± 0.3 mm/mm2) crack densities respectively. Based on distinct morphological features and characteristic length, we differentiate hot cracks from solid state cracks. Hot tears form at high angle grain boundaries and are associated with micron-sized gas pores as well as intermetallic phases in both samples. The solidification and cracking behaviour are modelled with the aid of a Scheil-Gulliver model that includes solute trapping. This approach predicts differences in hot-crack-susceptibilities, due to different solidification velocities, in line with experimental observations. The sample H, of high crack density, also experiences the higher cooling rate, and hence strain rate, which contributes to the greater propagation of cold cracks in the low fracture toughness AA2024. The observation of cracking associated with microporosity and the use of a Scheil-based solidification model, including solute trapping, provide new insights into the complex problem of hot tearing during L-PBF

Arterial stiffness, endothelial and cognitive function in subjects with type 2 diabetes in accordance with absence or presence of diabetic foot syndrome.

BACKGROUND: Endothelial dysfunction is an early marker of cardiovascular disease so endothelial and arterial stiffness indexes are good indicators of vascular health. We aimed to assess whether the presence of diabetic foot is associated with arterial stiffness and endothelial function impairment. METHODS: We studied 50 subjects with type 2 diabetes mellitus and diabetic foot syndrome (DFS) compared to 50 diabetic subjects without diabetic foot, and 53 patients without diabetes mellitus, by means of the mini mental state examination (MMSE) administered to evaluate cognitive performance. Carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) were also evaluated by Applanation tonometry (SphygmoCor version 7.1), and the RH-PAT data were digitally analyzed online by Endo-PAT2000 using reactive hyperemia index (RHI) values. RESULTS: In comparison to diabetic subjects without diabetic foot the subjects with diabetic foot had higher mean values of PWV, lower mean values of RHI, and lower mean MMSE. At multinomial logistic regression PWV and RHI were significantly associated with diabetic foot presence, whereas ROC curve analysis had good sensitivity and specificity in arterial PWV and RHI for diabetic foot presence. CONCLUSIONS: Pulse wave velocity and augmentation index, mean RHI values, and mean MMSE were effective indicators of diabetic foot. Future research could address these issues by means of longitudinal studies to evaluate cardiovascular event incidence in relation to arterial stiffness, endothelial and cognitive markers

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction

Background: Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. Aims: The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices. Methods: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5&nbsp;min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection. Results: 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance. Discussion: Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot

Choice of costimulatory domains and of cytokines determines CAR T-cell activity in neuroblastoma

Chimeric antigen receptor (CAR) T-cell therapy has been shown to be dramatically effective in the treatment of B-cell malignancies. However, there are still substantial obstacles to overcome, before similar responses can be achieved in patients with solid tumors. We evaluated both in vitro and in a preclinical murine model the efficacy of different 2nd and 3rd generation CAR constructs targeting GD2, a disial-ganglioside expressed on the surface of neuroblastoma (NB) tumor cells. In order to address potential safety concerns regarding clinical application, an inducible safety switch, namely inducible Caspase-9 (iC9), was also included in the vector constructs. Our data indicate that a 3rd generation CAR incorporating CD28.4-1BB costimulatory domains is associated with improved anti-tumor efficacy as compared with a CAR incorporating the combination of CD28.OX40 domains. We demonstrate that the choice of 4-1BB signaling results into significant amelioration of several CAR T-cell characteristics, including: 1) T-cell exhaustion, 2) basal T-cell activation, 3) in vivo tumor control and 4) T-cell persistence. The fine-tuning of T-cell culture conditions obtained using IL7 and IL15 was found to be synergic with the CAR.GD2 design in increasing the anti-tumor activity of CAR T cells. We also demonstrate that activation of the suicide gene iC9, included in our construct without significantly impairing neither CAR expression nor anti-tumor activity, leads to a prompt induction of apoptosis of GD2.CAR T cells. Altogether, these findings are instrumental in optimizing the function of CAR T-cell products to be employed in the treatment of children with NB

La tutela dei diritti umani in Europa tra sovranit\ue0 statale e ordinamenti sovranazionali

Il Volume si propone di offrire una visione dei sistemi di tutela dei diritti umani esistenti a livello europeo, pur nella consapevolezza che gli argomenti trattati non permettono di delineare un quadro esaustivo delle diverse problematiche. Nella scelta degli argomenti si \ue8 comunque tenuto conto di alcune delle principali questioni che animano l\u2019attuale dibattito scientifico. Nella redazione dell\u2019opera, a cui hanno partecipato diversi studiosi italiani e stranieri, si \ue8 perseguito l\u2019intento di coniugare il rigore dell\u2019indagine critica ad un\u2019attenzione particolare per le esigenze della didattica, al fine di offrire uno strumento rivolto non solo agli operatori giuridici, ma anche agli studenti universitari. In particolare, allo scopo di agevolare l\u2019uso didattico del Volume, si \ue8 ritenuto opportuno articolare l\u2019opera in cinque parti distinte, impiegabili indipendentemente l\u2019una dall\u2019altra ovvero secondo differenti combinazioni

The use of a P. falciparum specific coiled-coil domain to construct a self-assembling protein nanoparticle vaccine to prevent malaria.

The parasitic disease malaria remains a major global public health concern and no truly effective vaccine exists. One approach to the development of a malaria vaccine is to target the asexual blood stage that results in clinical symptoms. Most attempts have failed. New antigens such as P27A and P27 have emerged as potential new vaccine candidates. Multiple studies have demonstrated that antigens are more immunogenic and are better correlated with protection when presented on particulate delivery systems. One such particulate delivery system is the self-assembling protein nanoparticle (SAPN) that relies on coiled-coil domains of proteins to form stable nanoparticles. In the past we have used de novo designed amino acid domains to drive the formation of the coiled-coil scaffolds which present the antigenic epitopes on the particle surface. Here we use naturally occurring domains found in the tex1 protein to form the coiled-coil scaffolding of the nanoparticle. Thus, by engineering P27A and a new extended form of the coiled-coil domain P27 onto the N and C terminus of the SAPN protein monomer we have developed a particulate delivery system that effectively displays both antigens on a single particle that uses malaria tex1 sequences to form the nanoparticle scaffold. These particles are immunogenic in a murine model and induce immune responses similar to the ones observed in seropositive individuals in malaria endemic regions. We demonstrate that our P27/P27A-SAPNs induce an immune response akin to the one in seropositive individuals in Burkina Faso. Since P27 is highly conserved among different Plasmodium species, these novel SAPNs may even provide cross-protection between Plasmodium falciparum and Plasmodium vivax the two major human malaria pathogens. As the SAPNs are also easy to manufacture and store they can be delivered to the population in need without complication thus providing a low cost malaria vaccine