Innovative technology for cancer risk analysis

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Automotive leathers – evaluating the performance limits (part II)

Content: Consumers perceive leather as a durable and natural product. To support this positive image, car manufacturers have set demanding performance profiles addressing wear, emissions and sustainable manufacture. Poor performance of auto leather becomes visible as the polymeric finishing coat wears off or cracks over time. Therefore ageing property is seen as a representative key performance parameter and is determined by checking how flexible and strong a polymer coating remains after leather has been exposed to light, heat and humidity for a given time. Ageing of leather is complex to determine and depends on various parameters and requires a full system approach . In a first step different type of crusts (wet-blue, wet-white) were prepared and finished with a standard polyurethane coating. It turned out that the selection of the right fat liquors and tanning agents as well as the presence of vegetable tannins play an important role. On top of this the effective use of proper protective chemicals like anti-oxidants is needed. In a second approach the polymer coating itself was studied and optimized with regard to aged flexing and abrasion. Parameters like polymer type, crosslinking, application technology, coating thickness and impact of additives were investigated and tested when applied on the best crust leathers selected from part 1 of this work. Results show that not only is the right selection of polymers critical but also so is the way the coat is being applied . Furthermore coating thickness greatly defines wear (abrasion), lightfastness and ageing properties. Additives like dulling agents, levelers, feel agents, waxes ,fillers although needed can weaken the integrity of the polymer matrix and consequently reduce physical and chemical fastness properties. This may also apply to a certain extent to protective additives such as anti-oxidants and UV stabilizers, but when used properly their advantages outweigh the potential disadvantages. As to application, special emphasis is given to transfer coating technology which can provide advantages in application and quality consistency but also with regards to fastness properties such as wear and ageing. Take-Away: - crust leather has a critical impact on performance of finishing coat of automotive leathers and requires careful selction of products and use of protective chemical - polymer selection and use of protective chemical play an important role for achieving good aged flexing performance - type of application of finishing coat on auto leather further determines the performance of coatin

Neutrophils, Crucial, or Harmful Immune Cells Involved in Coronavirus Infection: A Bioinformatics Study

The latest member of the Coronaviridae family, called SARS-CoV-2, causes the Coronavirus Disease 2019 (COVID-19). The disease has caused a pandemic and is threatening global health. Similar to SARS-CoV, this new virus can potentially infect lower respiratory tract cells and can go on to cause severe acute respiratory tract syndrome, followed by pneumonia and even death in many nations. The molecular mechanism of the disease has not yet been evaluated until now. We analyzed the GSE1739 microarray dataset including 10 SARS-positive PBMC and four normal PBMC. Co-expression network analysis by WGCNA suggested that highly preserved 833 turquoise module with genes were significantly related to SARS-CoV infection. ELANE, ORM2, RETN, BPI, ARG1, DEFA4, CXCL1, and CAMP were the most important genes involved in this disease according to GEO2R analysis as well. The GO analysis demonstrated that neutrophil activation and neutrophil degranulation are the most activated biological processes in the SARS infection as well as the neutrophilia, basophilia, and lymphopenia predicted by deconvolution analysis of samples. Thus, using Serpins and Arginase inhibitors during SARS-CoV infection may be beneficial for increasing the survival of SARS-positive patients. Regarding the high similarity of SARS-CoV-2 to SARS-CoV, the use of such inhibitors might be beneficial for COVID-19 patients

How to better exploit the use of LCA analysis for Ultra High Performance Concrete (UHPC) through a constitutive law which integrates chloride and sulfate attack

Structural applications of advanced cementitious materials such as Ultra High Performance Concrete (UHPC) have been already assessed in harsh exposure conditions with presence of chlorides or sulfates. Nevertheless, the limited availability of design standards has not favoured so far a widespread use of these materials. Moreover, previous studies employed a constitutive model only partially representative of the real behavior of such materials when exposed to aggressive conditions. Therefore, this work, employing a “scenario dependent” constitutive law, estimates the serviceability limit state in correspondence of which it is needed to carry out the maintenance activities and investigates, through the Life Cycle Assessment (LCA) methodology, the ecological and economic profile of a UHPC water basin structure subjected to chloride and sulfate attack. The CML impact assessment method has been employed for the specific purpose to compare such structure to one made with ordinary reinforced concrete (ORC) using as system boundary the A1-B7 stages indicated in EN 15804

Muscle-only versus chimeric musculocutaneous gastrocnemius pedicled flap in complex orthoplastic reconstructions of the knee region: A retrospective study

Background: The knee region represents a challenging area of soft tissue reconstruction. Specifically, in the context of total knee arthroplasty (TKA) or following high-energy trauma with fractures and hardware fixation, soft tissue defects can expose critical structures such as joint, bone or tendon, besides the implant/plates themselves, with dramatic consequences in terms of postoperative infection and hardware contamination. Methods: A retrospective study was conducted on a prospectively maintained database from January 2016 to February 2021. Inclusion criteria involved all patients who underwent an implant-associated infection of the knee and upper third of the leg coupled with a soft tissue reconstruction (STR) using the traditional gastrocnemius muscle (GM) pedicled flap or the chimeric GM-MSAP (medial sural artery perforator) flap. Results: Thirty-eight patients were included (group A, GM flap, 22 patients; group B, chimeric GM-MSAP flap, 16 patients). No statistically significant differences were detected in terms of age, comorbidities, defect size, follow-up, and flap complications. A statistically significant difference was seen among the groups in terms of successful flap re-raise (required because of a persistent infection of the implant or in a two-stage procedure setting, including the use of a cemented spacer) in favour of the GM-MSAP group. Conclusion: The chimeric GM-MSAP, being safer to reraise if required, can be a significantly more powerful tool in those cases in which a two-stage procedure is planned or when there is a high probability for secondary intervention need, reducing the need to convert to either free flap coverage or amputation

One-Stage Coverage of Leg Region Defects with STSG Combined with VAC Dressing Improves Early Patient Mobilisation and Graft Take: A Comparative Study

Lower limb skin defects are very common and can result from a wide range of aetiologies. Split thickness skin graft (STSG) is a widely used method to address these problems. The role of postoperative dressing is primary as it permits one to apply a uniform pressure over the grafted area and promote adherence. Focusing on lower limb reconstruction, our clinical study compares the application of V.A.C. (Vacuum Assisted Closure) Therapy vs. conventional dressing in the immediate postoperative period following skin grafting. We included in the study all patients who received skin grafts on the leg region between January 2015 and December 2018, despite the aetiology of the defect. Only reconstructions with complete preoperative and postoperative follow-up data were included in the study. Patients were divided into two groups depending on if they received a traditional compressive dressing or a VAC dressing in the immediate postoperative period. We could retain 92 patients, 23 in the No VAC group and 69 in the VAC group. The patients included in the VAC group showed a statistically significant higher rate of graft take together with a lower immobilisation time (p < 0.05). Moreover, a lower rate of postoperative infection was recorded in the VAC group. This study represents the largest in the literature to report in detail surgical outcomes comparing the use of VAC therapy vs. conventional dressing after STSG in the postoperative management of lower limb reconstruction using skin grafts. VAC therapy was used to secure the grafts in the leg region, increasing the early graft take rate while at the same time improving patient mobilisation

The Genetic Germline Background of Single and Multiple Primary Melanomas

Background: Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. Materials and Methods: A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. Results: We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, p = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. Conclusions: In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM

The Genetic Germline Background of Single and Multiple Primary Melanomas

Background: Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. Materials and Methods: A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. Results: We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, p = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. Conclusions: In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM

Spectrum of germline pathogenic variants in brca1/2 genes in the apulian southern italy population: Geographic distribution and evidence for targeted genetic testing

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects

u-PAR expression in cancer associated fibroblast: new acquisitions in multiple myeloma progression

BACKGROUND: Multiple Myeloma (MM) is a B-cell malignancy in which clonal plasma cells progressively expand within the bone marrow (BM) as effect of complex interactions with extracellular matrix and a number of microenvironmental cells. Among these, cancer-associated fibroblasts (CAF) mediate crucial reciprocal signals with MM cells and are associated to aggressive disease and poor prognosis. A large body of evidence emphasizes the role of the urokinase plasminogen activator (u-PA) and its receptor u-PAR in potentiating the invasion capacity of tumor plasma cells, but little is known about their role in the biology of MM CAF. In this study, we investigated the u-PA/u-PAR axis in MM-associated fibroblasts and explore additional mechanisms of tumor/stroma interplay in MM progression. METHODS: CAF were purified from total BM stromal fraction of 64 patients including monoclonal gammopathy of undetermined significance, asymptomatic and symptomatic MM, as well as MM in post-treatment remission. Flow cytometry, Real Time PCR and immunofluorescence were performed to investigate the u-PA/u-PAR system in relation to the level of activation of CAF at different stages of the disease. Moreover, proliferation and invasion assays coupled with silencing experiments were used to prove, at functional level, the function of u-PAR in CAF. RESULTS: We found higher activation level, along with increased expression of pro-invasive molecules, including u-PA, u-PAR and metalloproteinases, in CAF from patients with symptomatic MM compared to the others stages of the disease. Consistently, CAF from active MM as well as U266 cell line under the influence of medium conditioned by active MM CAF, display higher proliferative rate and invasion potential, which were significantly restrained by u-PAR gene expression inhibition. CONCLUSIONS: Our data suggest that the stimulation of u-PA/u-PAR system contributes to the activated phenotype and function of CAF during MM progression, providing a biological rationale for future targeted therapies against MM