Epidermal Growth Factor Receptor Intron-1 Polymorphism Predicts Gefitinib Outcome in Advanced Non-small Cell Lung Cancer

IntroductionEpidermal growth factor receptor (EGFR) gene intron 1 contains a polymorphic single sequence dinucleotide repeat (CA)n whose length has been found to inversely correlate with transcriptional activity. This study was designed to assess the role of (CA)n polymorphism in predicting the outcome of gefitinib treatment in advanced non-small cell lung cancer (NSCLC).MethodsBlood and tumor tissue from 58 patients with advanced NSCLC submitted to gefitinib were collected. EGFR intron 1 gene polymorphism, along with EGFR gene mutation, gene copy number and immunohistochemistry expression were determined. Moreover, a panel of lung cancer cell lines characterized for EGFR intron 1 polymorphism was also studied.ResultsEGFR intron 1 polymorphism showed a statistically significant correlation with the gefitinib response (response rate 25 versus 0%, for patients with a (CA)16 and with a (CA)else genotype, respectively; p = 0.044). Patients with a (CA)16 genotype had a longer survival compared with those with a (CA)else genotype (11.4 versus 4.8 months, respectively; p = 0.037). In addition, cell lines lacking the (CA)16 allele showed a statistically significant higher IC50 compared with cell lines bearing at least one (CA)16 allele (p = 0.003).ConclusionsThis study supports a potential role of EGFR intron 1 polymorphism in predicting the outcome of gefitinib treatment in advanced NSCLC

An overview of monitoring methods for assessing the performance of nature-based solutions against natural hazards

To bring to fruition the capability of nature-based solutions (NBS) in mitigating hydro-meteorological risks (HMRs) and facilitate their widespread uptake require a consolidated knowledge-base related to their monitoring methods, efficiency, functioning and the ecosystem services they provide. We attempt to fill this knowledge gap by reviewing and compiling the existing scientific literature on methods, including ground-based measurements (e.g. gauging stations, wireless sensor network) and remote sensing observations (e.g. from topographic LiDAR, multispectral and radar sensors) that have been used and/or can be relevant to monitor the performance of NBS against five HMRs: floods, droughts, heatwaves, landslides, and storm surges and coastal erosion. These can allow the mapping of the risks and impacts of the specific hydro-meteorological events. We found that the selection and application of monitoring methods mostly rely on the particular NBS being monitored, resource availability (e.g. time, budget, space) and type of HMRs. No standalone method currently exists that can allow monitoring the performance of NBS in its broadest view. However, equipments, tools and technologies developed for other purposes, such as for ground-based measurements and atmospheric observations, can be applied to accurately monitor the performance of NBS to mitigate HMRs. We also focused on the capabilities of passive and active remote sensing, pointing out their associated opportunities and difficulties for NBS monitoring application. We conclude that the advancement in airborne and satellite-based remote sensing technology has signified a leap in the systematic monitoring of NBS performance, as well as provided a robust way for the spatial and temporal comparison of NBS intervention versus its absence. This improved performance measurement can support the evaluation of existing uncertainty and scepticism in selecting NBS over the artificially built concrete structures or grey approaches by addressing the questions of performance precariousness. Remote sensing technical developments, however, take time to shift toward a state of operational readiness for monitoring the progress of NBS in place (e.g. green NBS growth rate, their changes and effectiveness through time). More research is required to develop a holistic approach, which could routinely and continually monitor the performance of NBS over a large scale of intervention. This performance evaluation could increase the ecological and socio-economic benefits of NBS, and also create high levels of their acceptance and confidence by overcoming potential scepticism of NBS implementations

Prolonged pre-firing pancreatic compression with linear staplers in distal pancreatectomy: a valuable technique for post-operative pancreatic fistula prevention

Purpose: Post-operative pancreatic fistula (POPF) remains the main complication after distal pancreatectomy (DP). The aim of this study is to evaluate the potential benefit of different durations of progressive stapler closure on POPF rate and severity after DP. Methods: Patients who underwent DP between 2016 and 2023 were retrospectively enrolled and divided into two groups according to the duration of the stapler closure: those who underwent a progressive compression for < 10 min and those for ≥ 10 min. Results: Among 155 DPs, 83 (53.5%) patients underwent pre-firing compression for < 10 min and 72 (46.5%) for ≥ 10 min. As a whole, 101 (65.1%) developed POPF. A lower incidence rate was found in case of ≥ 10 min compression (34-47.2%) compared to < 10 min compression (67- 80.7%) (p = 0.001). When only clinically relevant (CR) POPFs were considered, a prolonged pre-firing compression led to a lower rate (15-20.8%) than the < 10 min cohort (32-38.6%; p = 0.02). At the multivariate analysis, a compression time of at least 10 min was confirmed as a protective factor for both POPF (OR: 5.47, 95% CI: 2.16-13.87; p = 0.04) and CR-POPF (OR: 2.5, 95% CI: 1.19-5.45; p = 0.04) development. In case of a thick pancreatic gland, a prolonged pancreatic compression for at least 10 min was significantly associated to a lower rate of CR-POPF compared to < 10 min (p = 0.04). Conclusion: A prolonged pre-firing pancreatic compression for at least 10 min seems to significantly reduce the risk of CR-POPF development. Moreover, significant advantages are documented in case of a thick pancreatic gland

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Mechanism of the pheromone-dependent plasmid transfer in Enterococci: role of proteins TraA and TraC obtained from a foodborne Enterococcus faecalis strain

In questo progetto di tesi di dottorato abbiamo dapprima condotto uno screening basato su PCR di ceppi di E. faecalis isolati da prodotti caseari allo scopo di valutare la diffusione dei plasmidi feromone-dipendenti più noti (pAD1, pCF10 e pPD1). Questi plasmidi possono essere coinvolti in una rapida diffusione di geni che codificano per antibiotico-resistenze e fattori di virulenza tra le popolazioni batteriche. I plasmidi pPD1 e pCF10 sono risultati ampiamente diffusi. Ci siamo quindi rivolti allo studio dei meccanismi molecolari alla base del trasferimento plasmidico coniugativo feromone-dipendente in E. faecalis. TraA e TraC, due proteine codificate dal plasmide pPD1 che svolgono un ruolo centrale in questo processo, sono state ottenute in forma ricombinante, e abbiamo studiato le loro interazioni con il feromone cPD1 e lo specifico inibitore iPD1, due peptidi che partecipano alla regolazione del processo di coniugazione. Nel caso di TraA sono state inoltre analizzate le interazioni con specifiche regioni del plasmide pPD1, modulate dalla presenza di cPD1 e iPD1, che sembrano essere alla base della regolazione dell’espressione dei geni coinvolti nel trasferimento plasmidico.In this PhD thesis project we have initially performed a PCR-based screening of foodborne E. faecalis strains to investigate the presence of major pheromone-dependent plasmids (pPD1, pAD1 and pCF10). These plasmids can be involved in the dissemination of virulence and antibiotic resistance traits among bacterial populations. We have found a wide distribution of plasmids pPD1 and pCF10 in the analyzed strains. To study molecular mechanisms of the pheromone-dependent plasmid transfer, TraA and TraC, two proteins that play a major role in this process, have been obtained as recombinant proteins and their interactions with the pheromone cPD1 and the specific inhibitor iPD1, two peptides involved in the regulation of the conjugation process, have been investigated. In the case of TraA we have also analyzed the interaction between TraA and specific regions of pPD1 both in the presence and in the absence of cPD1 and iPD1 regulator peptides; such interactions appear to be responsible for the regulation of the transcription of genes involved in the conjugation process

Supporting co-development phase of Nature Based Solution by combined use of Earth Observation and modeling

A protected natural area in the Emilia Romagna region, Northern Italy is threatened by hydro-meteorological hazards, particularly sea storms. In the last 50 years the northern part of the Bellocchio Park (Sacca Bellocchio II Nature Reserve, Site code EUAPP0072 - Ferrara, Italy) was interested by an intensive urbanization (Lido di Spina) with the realization of infrastructures, e.g. roads and residential settlements. This land use change led to the construction of embankments and to the conversion of wetlands. These modifications, in combination to even more frequent storm surge events increased coastal erosion. In addition, inland flooding caused by storm surges acts with the reduction of the lagoon and the increase of soil salinity. As an example, the last event occurred in December 2020 eroded a large portion of the Bellocchio beach. Co-design, co-development and deployment of NBS solutions to reduce storm surge risk in the Bellocchio Park is one of the objectives of the H2020 project OPEn-air laboRAtories for Nature baseD solUtions to Manage environmental risks (OPERANDUM). BellocchioBellochio park is in fact one of the 10 Open Air Laboratories (OAL) where the evidence of mitigation of hydro-meteorological risk by NBS will be demonstrated by the combination of different models, approaches and data.During the co-design process in the Bellocchio park, potential deployment locations of sand dunes have been identified in collaboration with local authorities devoted to the management of the natural area and to the coast defense (CB and ARSTePC-RER) and an environmental engineering consultant assisting Arpae (IRIS sas). Field visits were devoted to the analysis of the environmental features, strengths and weaknesses of candidate sites.This work aims to explore the usefulness of the combined use of multisource remote sensing and modeling in decision making during the co-design process of a NBS. The impacts of the most intense extreme storm surge events in the last 30 years have been documented by delineating flooded areas along the coast using Synthetic Aperture Radar and Multispectral image data. Coastal erosion has been also described by means of change detection analysis and very high resolution multispectral EO data. This screening has given a picture of areas at the risk, i.e. the area most likely to be affected by storm-surge events. Auxiliary data like Digital Terrain Models has been assimilated in a dedicated model to produce flood maps under different scenarios, i.e. different locations and size of NBS and different intensities of storm surge. The integrated analysis was helpful in defining the priority sites, among the ones defined by the stakeholders and engineers, in term of effectiveness for storm surge risk reduction.Optical and Laser Remote SensingGeo-engineerin

Structural and mutational analyses of protein-protein interactions between transthyretin and retinol-binding protein

Transthyretin is a tetrameric binding protein involved in the transport of thyroid hormones and in the cotransport of retinol by forming a complex in plasma with retinol-binding protein. in the present study, we report the crystal structure of a macromolecular complex, in which human transthyretin, human holo-retinol-binding protein and a murine anti-retinol-binding protein Fab are assembled according to a 1 : 2 : 2 stoichiometry. the main interactions, both polar and apolar, between retinol-binding protein and transthyretin involve the retinol hydroxyl group and a limited number of solvent exposed residues. the relevance of transthyretin residues in complex formation with retinol-binding protein has been examined by mutational analysis, and the structural consequences of some transthyretin point mutations affecting protein-protein recognition have been investigated. Despite a few exceptions, in general, the substitution of a hydrophilic for a hydrophobic side chain in contact regions results in a decrease or even a loss of binding affinity, thus revealing the importance of interfacial hydrophobic interactions and a high degree of complementarity between retinol-binding protein and transthyretin. the effect is particularly evident when the mutation affects an interacting residue present in two distinct subunits of transthyretin participating simultaneously in two interactions with a retinol-binding protein molecule. This is the case of the amyloidogenic I84S replacement, which abolishes the interaction with retinol-binding protein and is associated with an altered retinol-binding protein plasma transport in carriers of this mutation. Remarkably, some of the residues in mutated human transthyretin that weaken or abolish the interaction with retinol-binding protein are present in piscine transthyretin, consistent with the lack of interaction between retinol-binding protein and transthyretin in fish.PRIN Projects of the 'Ministero dell'Universita e della Ricerca' (Rome, Italy)Universities of Parma and Padua, ItalyUniv Parma, Dept Biochem & Mol Biol, I-43100 Parma, ItalyUniv Padua, Inst Biomol Chem, CNR, I-35131 Padua, ItalyUniv Padua, Dept Chem Sci, I-35131 Padua, ItalyVenetian Inst Mol Med, Padua, ItalyUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilUniv Padua, Dept Expt Vet Sci, I-35100 Padua, ItalyUniv Padua, CRIBI, I-35100 Padua, ItalyUniversidade Federal de São Paulo, Dept Med, São Paulo, BrazilWeb of Scienc

Tetracalcium phosphate and biphasic tetracalcium phosphate/tricalcium phosphate powders' effects evaluation on human osteoblasts.

BACKGROUND Calcium ions levels in bone niches have been demonstrated to severely influence new bone formation. Osteoinductive scaffolds containing calcium have been largely studied to control the release of calcium in bone regeneration and tissue engineering purpose. The aim of the present study was, firstly, to synthesize two different resorbable calcium phosphate-based powders, thought to be reservoirs of calcium ions, and secondary, to investigate their effects on human osteoblasts, in order to develop a suitable titanium coating material. METHODS Tetracalcium phosphate (A450) and biphasic tetracalcium phosphatae/tricalcium phosphate (A850) powders were prepared with an innovative method. The presence of calcium phosphate structures was chemically confirmed with XRD. Furthermore, powders macroscopic aspect was observed with a stereomicroscope. For in-vitro experiments, human osteoblastic cells were cultured in the presence of A450 and A850, and assayed for viability and metabolic activity through Crystal Violet and MTT, respectively. RESULTS Our synthesis led to the formation of calcium phosphates in both samples, even though A850 presented a higher level of crystallinity and a more powdery aspects than A450. Both the samples enhanced the viability of cultured cells, inhibiting cell metabolic activity in the case of A850, which furthermore showed to be internalized by cells. CONCLUSIONS We developed two different kind of calcium phosphate-based powders and we tested their effect on human osteoblasts, underlying the possibility of use calcium phosphate-based coatings to enhance cell response on implantable materials

Blood Stream Infections from MDR Bacteria

Bloodstream infections (BSIs) constitute a growing public health concern, are among the most severe nosocomial pathologies, and are considered a worldwide cause of unfaithful outcomes, increasing treatment costs and diagnostic uncertainties. BSIs are one of the most frequent lethal conditions that are managed in intensive care units (ICUs). In the case of septic shock, immune deficiency, and delayed treatment, even with adequate antimicrobial therapy and/or source control, the outcomes are often unfavorable