Elastin-like-recombinamers multilayered nanofibrous scaffolds for cardiovascular applications

Producción CientíficaCoronary angioplasty is the most widely used technique for removing atherosclerotic plaques in blood vessels. The regeneration of the damaged intima layer after this treatment is still one of the major challenges in the field of cardiovascular tissue engineering. Different polymers have been used in scaffold manufacturing in order to improve tissue regeneration. Elastin-mimetic polymers are a new class of molecules that have been synthesized and used to obtain small diameter fibers with specific morphological characteristics. Elastin-like polymers produced by recombinant techniques and called elastin-like recombinamers (ELRs) are particularly promising due to their high degree of functionalization. Generally speaking, ELRs can show more complex molecular designs and a tighter control of their sequence than other chemically synthetized polymers Rodriguez Cabello et al (2009 Polymer 50 5159–69, 2011 Nanomedicine 6 111–22). For the fabrication of small diameter fibers, different ELRs were dissolved in 2,2,2-fluoroethanol (TFE). Dynamic light scattering was used to identify the transition temperature and get a deep characterization of the transition behavior of the recombinamers. In this work, we describe the use of electrospinning technique for the manufacturing of an elastic fibrous scaffold; the obtained fibers were characterized and their cytocompatibility was tested in vitro. A thorough study of the influence of voltage, flow rate and distance was carried out in order to determine the appropriate parameters to obtain fibrous mats without beads and defects. Moreover, using a rotating mandrel, we fabricated a tubular scaffold in which ELRs containing different cell adhesion sequences (mainly REDV and RGD) were collected. The stability of the scaffold was improved by using genipin as a crosslinking agent. Genipin-ELRs crosslinked scaffolds show a good stability and fiber morphology. Human umbilical vein endothelial cells were used to assess the in vitro bioactivity of the cell adhesion domains within the backbone of the ELRs.2018-08-0

Awake Fiberoptic Intubation Protocols in the Operating Room for Anticipated Difficult Airway: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Awake fiberoptic intubation is one of the recommended strategies for surgical patients with anticipated difficult airway, especially when concurrent difficult ventilation is expected. We performed the first systematic review of randomized controlled trials assessing different protocols for awake fiberoptic intubation in anticipated difficult airway, including studies investigating elective awake fiberoptic intubation for scheduled surgery; randomized controlled trials comparing different methods for performing awake fiberoptic intubation; and adult patients with anticipated difficult airway. We excluded studies in the nonoperating theater settings, randomized controlled trials comparing awake fiberoptic intubation with other techniques, and studies based on simulation. Primary outcomes were success rate and death; secondary outcomes were major adverse events. Thirty-seven randomized controlled trials evaluating 2045 patients and 4 areas were identified: premedication, local anesthesia, sedation, and ancillary techniques to facilitate awake fiberoptic intubation. Quality of evidence was moderate-low and based on small-sampled randomized controlled trials. Overall, 12 of 2045 intubation failures (0.59%) and 7 of 2045 severe adverse events (0.34%) occurred, with no permanent consequences or death. All evaluated methods to achieve local anesthesia performed similarly well. No differences were observed in success rate with different sedatives. Dexmedetomidine resulted in fewer desaturation episodes compared to propofol and opioids with or without midazolam (relative risk, 0.51 [95% CI, 0.28-0.95]; P = .03); occurrence of desaturation was similar with remifentanil versus propofol, while incidence of apnoea was lower with sevoflurane versus propofol (relative risk, 0.43 [95% CI, 0.22-0.81]; P = .01). A high degree of efficacy and safety was observed with minimal differences among different protocols; dexmedetomidine might offer a better safety profile compared to other sedatives

Fluoro-edenitic fibres in the sputum of subjects from Biancavilla (Sicily): a pilot study

BACKGROUND: An excess of mortality for malignant neoplasms of the pleura in Biancavilla, promoted an investigation for pleural mesothelioma, disclosing 17 cases. As the absence of known sources of asbestos exposure, a local stone quarry, located near the inhabited area, used for the extraction of building materials, was investigated. Amphibolic fibres were found in the quarry and identified as fluoro-edenite "new end-member of the edenite / fluoro-edenite series" and recognized as the fluoro-edenite holotype by International Mineralogical Association – Commission on New Minerals and Mineral Names. A pilot study was performed to verify the feasibility of using spontaneous sputum as an exposure indicator for these fibres, in a context in which the use of aerosol-induced sputum technique would not be easily accepted. METHODS: Hypothesizing a behaviour of the new fibre analogous to that of asbestos, the determination of the free fibres and the ferruginous bodies in spontaneous sputum was carried out. Phase Contrast Optical Microscope and an Environmental Scanning Electron Microscope fitted with X-ray energy dispersive analysis system (micro-analysis) were used to examine the samples. The criteria for inclusion in the study were: 1) subjects hospitalized for exacerbation of chronic obstructive pulmonary disease symptoms, 2) age ≥ 45 years, 3) residence in Biancavilla for at least 30 years. RESULTS: The preliminary findings are related to 12 subjects (7 females and 5 males). Uncoated fibres (with length > 5 μm, diameter < 3 μm, aspect ratio 3.1) and ferruginous bodies were searched. Six out of twelve subjects (4 females, 2 males) had at least one of the three samples positive for the presence of fluoro-edenite, confirmed by micro-analysis. The fibre concentration found in the sputum ranged from 0.04 to 10 fibres/g; the length from 20 to 40 μm, the diameter was < 0.5 μm. No ferruginous bodies were found in any of the samples. The four women with a positive sample were housewives. Of the two men with a positive sample, one was a farmer and the other a mason. Therefore, it may be assumed that the exposure to fluoro-edenitic fibres was mainly environmental. CONCLUSION: The occurrence of the pleural mesothelioma cases and the presence of fluoro-edenitic fibres in spontaneous sputum, evidence the need to study the biological activity of fluoro-edenitic fibres and the implementation of epidemiological monitoring systems

Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer

BACKGROUND: The randomised phase III TANIA trial demonstrated that continuing bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC) after progression on first-line bevacizumab-containing therapy significantly improved progression-free survival (PFS) compared with chemotherapy alone (hazard ratio [HR]=0.75, 95% confidence interval [CI] 0.61-0.93). We report final results from the TANIA trial, including overall survival (OS) and health-related quality of life (HRQoL). PATIENTS AND METHODS: Patients with HER2-negative LR/mBC that had progressed on or after first-line bevacizumab plus chemotherapy were randomised to receive standard second-line chemotherapy either alone or with bevacizumab. At second progression, patients initially randomised to bevacizumab continued bevacizumab with their third-line chemotherapy but those randomised to chemotherapy alone were not allowed to cross over to receive third-line bevacizumab. The primary end point was second-line PFS; secondary end points included third-line PFS, combined second- and third-line PFS, OS, HRQoL and safety. RESULTS: Of the 494 patients randomised, 483 received second-line therapy; 234 patients (47% of the randomised population) continued to third-line study treatment. The median duration of follow-up at the final analysis was 32.1 months in the chemotherapy-alone arm and 30.9 months in the bevacizumab plus chemotherapy arm. There was no statistically significant difference between treatment arms in third-line PFS (HR=0.79, 95% CI 0.59-1.06), combined second- and third-line PFS (HR=0.85, 95% CI 0.68-1.05) or OS (HR=0.96, 95% CI 0.76-1.21). Third-line safety results showed increased incidences of proteinuria and hypertension with bevacizumab, consistent with safety results for the second-line treatment phase. No differences in HRQoL were detected. CONCLUSION: In this trial, continuing bevacizumab beyond first and second progression of LR/mBC improved second-line PFS but no improvement in longer-term efficacy was observed. The second-line PFS benefit appears to be achieved without detrimentally affecting quality of life. CLINICALTRIALSGOV: NCT01250379

Accumulation of neutral lipids in peripheral blood mononuclear cells as a distinctive trait of Alzheimer patients and asymptomatic subjects at risk of disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease is the most common progressive neurodegenerative disease. In recent years, numerous progresses in the discovery of novel Alzheimer's disease molecular biomarkers in brain as well as in biological fluids have been made. Among them, those involving lipid metabolism are emerging as potential candidates. In particular, an accumulation of neutral lipids was recently found by us in skin fibroblasts from Alzheimer's disease patients. Therefore, with the aim to assess whether peripheral alterations in cholesterol homeostasis might be relevant in Alzheimer's disease development and progression, in the present study we analyzed lipid metabolism in plasma and peripheral blood mononuclear cells from Alzheimer's disease patients and from their first-degree relatives.</p> <p>Methods</p> <p>Blood samples were obtained from 93 patients with probable Alzheimer's disease and from 91 of their first-degree relatives. As controls we utilized 57, cognitively normal, over-65 year-old volunteers and 113 blood donors aged 21-66 years, respectively. Data are reported as mean ± standard error. Statistical calculations were performed using the statistical analysis software Origin 8.0 version. Data analysis was done using the Student t-test and the Pearson test.</p> <p>Results</p> <p>Data reported here show high neutral lipid levels and increased ACAT-1 protein in about 85% of peripheral blood mononuclear cells freshly isolated (<it>ex vivo</it>) from patients with probable sporadic Alzheimer's disease compared to about 7% of cognitively normal age-matched controls. A significant reduction in high density lipoprotein-cholesterol levels in plasma from Alzheimer's disease blood samples was also observed. Additionally, correlation analyses reveal a negative correlation between high density lipoprotein-cholesterol and cognitive capacity, as determined by Mini Mental State Examination, as well as between high density lipoprotein-cholesterol and neutral lipid accumulation. We observed great variability in the neutral lipid-peripheral blood mononuclear cells data and in plasma lipid analysis of the subjects enrolled as Alzheimer's disease-first-degree relatives. However, about 30% of them tend to display a peripheral metabolic cholesterol pattern similar to that exhibited by Alzheimer's disease patients.</p> <p>Conclusion</p> <p>We suggest that neutral lipid-peripheral blood mononuclear cells and plasma high density lipoprotein-cholesterol determinations might be of interest to outline a distinctive metabolic profile applying to both Alzheimer's disease patients and asymptomatic subjects at higher risk of disease.</p

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening